{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:10:37Z","timestamp":1792797037387,"version":"4.5.0"},"reference-count":300,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,1,24]],"date-time":"2018-01-24T00:00:00Z","timestamp":1516752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Over-the-counter (OTC) analgesics are among the most widely prescribed and purchased drugs around the world. Most analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, are metabolized in the liver. The hepatocytes are responsible for drug metabolism and detoxification. Cytochrome P450 enzymes are phase I enzymes expressed mainly in hepatocytes and they account for \u224875% of the metabolism of clinically used drugs and other xenobiotics. These metabolic reactions eliminate potentially toxic compounds but, paradoxically, also result in the generation of toxic or carcinogenic metabolites. Cumulative or overdoses of OTC analgesic drugs can induce acute liver failure (ALF) either directly or indirectly after their biotransformation. ALF is the result of massive death of hepatocytes induced by oxidative stress. There is an increased interest in the use of natural dietary products as nutritional supplements and\/or medications to prevent or cure many diseases. The therapeutic activity of natural products may be associated with their antioxidant capacity, although additional mechanisms may also play a role (e.g., anti-inflammatory actions). Dietary antioxidants such as flavonoids, betalains and carotenoids play a preventive role against OTC analgesics-induced ALF. In this review, we will summarize the pathobiology of OTC analgesic-induced ALF and the use of natural pigments in its prevention and therapy.<\/jats:p>","DOI":"10.3390\/nu10020117","type":"journal-article","created":{"date-parts":[[2018,1,24]],"date-time":"2018-01-24T09:47:36Z","timestamp":1516787256000},"page":"117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Natural Dietary Pigments: Potential Mediators against Hepatic Damage Induced by Over-The-Counter Non-Steroidal Anti-Inflammatory and Analgesic Drugs"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5202-4624","authenticated-orcid":false,"given":"Herson","family":"Gonz\u00e1lez-Ponce","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6834-7129","authenticated-orcid":false,"given":"Ana","family":"Rinc\u00f3n-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genomics, University Center of Health Sciences, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Jaramillo-Ju\u00e1rez","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Basic Science Center, Universidad Aut\u00f3noma de Aguascalientes, Aguascalientes 20131, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4764-0246","authenticated-orcid":false,"given":"Han","family":"Moshage","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands"},{"name":"Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E239","DOI":"10.1007\/BF02854894","article-title":"Drug discovery from natural sources","volume":"8","author":"Chin","year":"2006","journal-title":"AAPS J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1021\/np068054v","article-title":"Natural Products as Sources of New Drugs over the Last 25 Years","volume":"70","author":"Newman","year":"2007","journal-title":"J. Nat. Prod."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1039\/a902202c","article-title":"The influence of natural products upon drug discovery (Antiquity to late 1999)","volume":"17","author":"Newman","year":"2000","journal-title":"Nat. Prod. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Gu, J., Gui, Y., Chen, L., Yuan, G., Lu, H.-Z., and Xu, X. (2013). Use of Natural Products as Chemical Library for Drug Discovery and Network Pharmacology. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0062839"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.phymed.2007.03.017","article-title":"Betanin a betacyanin pigment purified from fruits of Opuntia ficus-indica induces apoptosis in human chronic myeloid leukemia Cell line-K562","volume":"14","author":"Sreekanth","year":"2007","journal-title":"Phytomedicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1002\/cbf.3104","article-title":"Cranberry flavonoids prevent toxic rat liver mitochondrial damage in vivo and scavenge free radicals in vitro: Cranberry flavonoids prevent mitochondrial damage and scavenge free radicals","volume":"33","author":"Lapshina","year":"2015","journal-title":"Cell Biochem. Funct."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Ponce, H., Mart\u00ednez-Salda\u00f1a, M., Rinc\u00f3n-S\u00e1nchez, A., Sumaya-Mart\u00ednez, M., Buist-Homan, M., Faber, K.N., Moshage, H., and Jaramillo-Ju\u00e1rez, F. (2016). Hepatoprotective Effect of Opuntia robusta and Opuntia streptacantha Fruits against Acetaminophen-Induced Acute Liver Damage. Nutrients, 8.","DOI":"10.3390\/nu8100607"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.freeradbiomed.2015.12.024","article-title":"Caffeic acid prevents acetaminophen-induced liver injury by activating the Keap1-Nrf2 antioxidative defense system","volume":"91","author":"Pang","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Dewick, P.M. (2009). Medicinal Natural Products: A Biosynthetic Approach, John Wiley and Sons, Ltd.. [3rd ed.].","DOI":"10.1002\/9780470742761"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3390\/metabo2020303","article-title":"A Historical Overview of Natural Products in Drug Discovery","volume":"2","author":"Dias","year":"2012","journal-title":"Metabolites"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Donovan, J.L., Manach, C., Faulks, R.M., and Kroon, P.A. (2006). Absorption and metabolism of dietary plant secondary metabolites. Plant Secondary Metabolites Occurrence, Structure and Role in the Human Diet, Blackwell Publishing Ltd.","DOI":"10.1002\/9780470988558.ch8"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.mam.2010.09.007","article-title":"Bioavailability of dietary flavonoids and phenolic compounds","volume":"31","author":"Crozier","year":"2010","journal-title":"Mol. Asp. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.cbpa.2011.03.004","article-title":"Role of natural product diversity in chemical biology","volume":"15","author":"Hong","year":"2011","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1021\/np100550t","article-title":"Modern Natural Products Drug Discovery and Its Relevance to Biodiversity Conservation","volume":"74","author":"Kingston","year":"2011","journal-title":"J. Nat. Prod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/nrd1657","article-title":"The evolving role of natural products in drug discovery","volume":"4","author":"Koehn","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1021\/ci0200467","article-title":"Property Distributions: Differences between Drugs, Natural Products, and Molecules from Combinatorial Chemistry","volume":"43","author":"Feher","year":"2003","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.semarthrit.2008.08.001","article-title":"Nonsteroidal Anti-Inflammatory Drugs: Adverse Effects and Their Prevention","volume":"39","author":"Vonkeman","year":"2010","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Fendrick, A.M., Pan, D.E., and Johnson, G.E. (2008). OTC analgesics and drug interactions: Clinical implications. Osteopath. Med. Prim. Care, 2.","DOI":"10.1186\/1750-4732-2-2"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"911","DOI":"10.3109\/15563650.2012.746424","article-title":"2011 Annual Report of the American Association of Poison Control Centers\u2019 National Poison Data System (NPDS): 29th Annual Report","volume":"50","author":"Bronstein","year":"2012","journal-title":"Clin. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1002\/pds.1191","article-title":"Estimates of acetaminophen (paracetamol)-associated overdoses in the United States","volume":"15","author":"Nourjah","year":"2006","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.mcna.2008.03.005","article-title":"Acute Liver Failure including Acetaminophen Overdose","volume":"92","author":"Fontana","year":"2008","journal-title":"Med. Clin. N. Am."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Poljsak, B., \u0160uput, D., and Milisav, I. (2013). Achieving the Balance between ROS and Antioxidants: When to Use the Synthetic Antioxidants. Oxid. Med. Cell. Longev., 2013.","DOI":"10.1155\/2013\/956792"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1053\/ajem.2002.32643","article-title":"The high prevalence of pain in emergency medical care","volume":"20","author":"Cordell","year":"2002","journal-title":"Am. J. Emerg. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e010184","DOI":"10.1136\/bmjopen-2015-010184","article-title":"How adolescents experience and cope with pain in daily life: A qualitative study on ways to cope and the use of over-the-counter analgesics","volume":"6","author":"Rosvold","year":"2016","journal-title":"BMJ Open"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/S0149-2918(00)80043-0","article-title":"Over-the-counter analgesics and antipyretics: A critical assessment","volume":"22","author":"Hersh","year":"2000","journal-title":"Clin. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.sapharm.2013.06.004","article-title":"Swedish teenagers and over-the-counter analgesics\u2014Responsible, casual or careless use","volume":"10","author":"Bernsten","year":"2014","journal-title":"Res. Soc. Adm. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1016\/j.clinthera.2007.12.003","article-title":"Adverse drug interactions involving common prescription and over-the-counter analgesic agents","volume":"29","author":"Hersh","year":"2007","journal-title":"Clin. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.annemergmed.2005.12.012","article-title":"Overuse of Over-the-Counter Analgesics by Emergency Department Patients","volume":"48","author":"Heard","year":"2006","journal-title":"Ann. Emerg. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Goh, L.Y., Vitry, A.I., Semple, S.J., Esterman, A., and Luszcz, M.A. (2009). Self-medication with over-the-counter drugs and complementary medications in South Australia\u2019s elderly population. BMC Complement. Altern. Med., 9.","DOI":"10.1186\/1472-6882-9-42"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.annemergmed.2004.05.005","article-title":"Prospective evaluation of repeated supratherapeutic acetaminophen (paracetamol) ingestion","volume":"44","author":"Daly","year":"2004","journal-title":"Ann. Emerg. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1001\/jama.287.3.337","article-title":"Recent patterns of medication use in the ambulatory adult population of the United States: The slone survey","volume":"287","author":"Kaufman","year":"2002","journal-title":"JAMA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/ijcp.12048","article-title":"Gastrointestinal safety of NSAIDs and over-the-counter analgesics: Gastrointestinal safety of NSAIDs and over-the-counter analgesics","volume":"67","author":"Bjarnason","year":"2013","journal-title":"Int. J. Clin. Pract."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Sarganas, G., Buttery, A.K., Zhuang, W., Wolf, I.-K., Grams, D., Rosario, A.S., Scheidt-Nave, C., and Knopf, H. (2015). Prevalence, trends, patterns and associations of analgesic use in Germany. BMC Pharmacol. Toxicol., 16.","DOI":"10.1186\/s40360-015-0028-7"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"245","DOI":"10.2165\/11596000-000000000-00000","article-title":"Targeting Outpatient Drug Safety","volume":"35","author":"Kramers","year":"2012","journal-title":"Drug Saf."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e191","DOI":"10.3399\/bjgp14X677815","article-title":"High-risk use of over-the-counter non-steroidal anti-inflammatory drugs: A population-based cross-sectional study","volume":"64","author":"Koffeman","year":"2014","journal-title":"Br. J. Gen. Pract."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1097\/00002508-198602010-00008","article-title":"Survey of Pain in the United States: The Nuprin Pain Report","volume":"2","author":"Sternbach","year":"1986","journal-title":"Clin. J. Pain"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1017\/S0317167100047697","article-title":"Impact of Migraine and Tension-Type Headache on Life-Style, Consulting Behaviour, and Medication Use: A Canadian Population Survey","volume":"20","author":"Edmeads","year":"1993","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1136\/bmj.295.6604.962","article-title":"Repeat prescribing of non-steroidal anti-inflammatory drugs excluding aspirin: How careful are we?","volume":"295","author":"Steele","year":"1987","journal-title":"Br. Med. J. Clin. Res. Ed."},{"key":"ref_39","first-page":"13","article-title":"Use and abuse of over-the-counter analgesic agents","volume":"23","author":"Abbott","year":"1998","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1080\/03602532.2017.1354014","article-title":"Paracetamol: Overdose-induced oxidative stress toxicity, metabolism and protective effects of various compounds in vivo and in vitro","volume":"49","author":"Wang","year":"2017","journal-title":"Drug Metabol. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.psychres.2013.03.037","article-title":"Suicide attempts by deliberate self-poisoning in children and adolescents","volume":"210","author":"Zakharov","year":"2013","journal-title":"Psychiatry Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1007\/s11606-012-2096-3","article-title":"Risk of Unintentional Overdose with Non-Prescription Acetaminophen Products","volume":"27","author":"Wolf","year":"2012","journal-title":"J. Gen. Intern. Med."},{"key":"ref_43","first-page":"1061","article-title":"Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs","volume":"11","author":"Moore","year":"2015","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/j.1365-2710.2004.00607.x","article-title":"Prevalence of over-the-counter drug-related overdoses at Accident and Emergency departments in Northern Ireland\u2014A retrospective evaluation","volume":"30","author":"Wazaify","year":"2005","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.matbio.2015.01.004","article-title":"Matrix metalloproteinases in liver injury, repair and fibrosis","volume":"44\u201346","author":"Duarte","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.devcel.2010.01.011","article-title":"Organogenesis and Development of the Liver","volume":"18","author":"Lemaigre","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_47","unstructured":"Correa, P.R.A., and Nathanson, M.H. (2007). Functions of the liver. Textbook of Hepatology: From Basic Science to Clinical Practice, Blackwell Publishing Ltd.. [3rd ed.]. Chapter 2.2."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Kmie\u0107, Z. (2001). Introduction\u2014Morphology of the Liver Lobule. Cooperation of Liver Cells in Health and Disease, Springer. Available online: http:\/\/dx.doi.org\/10.1007\/978-3-642-56553-3_1.","DOI":"10.1007\/978-3-642-56553-3_1"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1055\/s-2007-991515","article-title":"Hepatic Microvasculature in Liver Injury","volume":"27","author":"DeLeve","year":"2007","journal-title":"Semin. Liver Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-pathol-011110-130246","article-title":"Pathogenesis of Liver Fibrosis","volume":"6","author":"Friedman","year":"2011","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_51","unstructured":"Terjung, R. (2013). Apoptosis and Necrosis in the Liver. Comprehensive Physiology, John Wiley & Sons, Inc.. Available online: http:\/\/doi.wiley.com\/10.1002\/cphy.c120020."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/0163-7258(92)90055-5","article-title":"Metabolic zonation of the liver: Regulation and implications for liver function","volume":"53","author":"Gebhardt","year":"1992","journal-title":"Pharmacol. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1146\/annurev.pharmtox.45.120403.100007","article-title":"Cytochrome P450 and xenobiotic receptor humanized mice","volume":"46","author":"Gonzalez","year":"2006","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1152\/physrev.00027.2008","article-title":"The Hepatic Microcirculation: Mechanistic Contributions and Therapeutic Targets in Liver Injury and Repair","volume":"89","author":"Vollmar","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/nri3169","article-title":"Living in the liver: Hepatic infections","volume":"12","author":"Protzer","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"6990","DOI":"10.3390\/ijms15046990","article-title":"Drug-Induced Hepatotoxicity: Metabolic, Genetic and Immunological Basis","volume":"15","author":"Njoku","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/S0140-6736(02)11203-7","article-title":"Clinical importance of the cytochromes P450","volume":"360","author":"Nebert","year":"2002","journal-title":"Lancet"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1124\/mi.3.4.194","article-title":"Cytochromes P450, drugs, and diseases","volume":"3","author":"Guengerich","year":"2003","journal-title":"Mol. Interv."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"257","DOI":"10.2133\/dmpk.21.257","article-title":"Xenobiotic-Metabolizing Enzymes Involved in Activation and Detoxification of Carcinogenic Polycyclic Aromatic Hydrocarbons","volume":"21","author":"Shimada","year":"2006","journal-title":"Drug Metab. Pharmacokinet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/BF02977789","article-title":"Induction of phase I, II and III drug metabolism\/transport by xenobiotics","volume":"28","author":"Xu","year":"2005","journal-title":"Arch. Pharm. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/aja.1001750406","article-title":"Peri- and postnatal development of heterogeneity in the amounts of endoplasmic reticulum in mouse hepatocytes","volume":"175","author":"Kanai","year":"1986","journal-title":"Am. J. Anat."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/0006-291X(74)90418-5","article-title":"Role of superoxide radical in mitochondrial dehydrogenase reactions","volume":"60","author":"Forman","year":"1974","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/0014-5793(74)80281-4","article-title":"Superoxide radicals as precursors of mitochondrial hydrogen peroxide","volume":"42","author":"Loschen","year":"1974","journal-title":"FEBS Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1104\/pp.106.077073","article-title":"Reactive Species and Antioxidants. Redox Biology Is a Fundamental Theme of Aerobic Life","volume":"141","author":"Halliwell","year":"2006","journal-title":"Plant Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/geronj\/11.3.298","article-title":"Aging: A Theory Based on Free Radical and Radiation Chemistry","volume":"11","author":"Harman","year":"1956","journal-title":"J. Gerontol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"6049","DOI":"10.1016\/S0021-9258(18)63504-5","article-title":"Superoxide dismutase an enzymic function for erythrocuprein (hemocuprein)","volume":"244","author":"McCord","year":"1969","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/35041687","article-title":"Oxidants, oxidative stress and the biology of ageing","volume":"408","author":"Finkel","year":"2000","journal-title":"Nature"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1084\/jem.192.7.1001","article-title":"Reactive oxygen species (ROS-induced) ROS release","volume":"192","author":"Zorov","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gene.2004.04.032","article-title":"Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells","volume":"337","author":"Boonstra","year":"2004","journal-title":"Gene"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/0925-4439(95)00029-4","article-title":"Protective roles of cytokines against radiation: Induction of mitochondrial MnSOD","volume":"1271","author":"Wong","year":"1995","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2007.09.022","article-title":"NF-\u03baB-mediated adaptive resistance to ionizing radiation","volume":"44","author":"Li","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1007\/s12072-009-9158-6","article-title":"Role of free radicals in liver diseases","volume":"3","author":"Muriel","year":"2009","journal-title":"Hepatol. Int."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1152\/physrev.00018.2001","article-title":"Free Radicals in the Physiological Control of Cell Function","volume":"82","year":"2002","journal-title":"Physiol. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"C246","DOI":"10.1152\/ajpcell.00516.2003","article-title":"Redox signaling: Thiol chemistry defines which reactive oxygen and nitrogen species can act as second messengers","volume":"287","author":"Forman","year":"2004","journal-title":"Am. J. Physiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1023\/A:1027374931887","article-title":"Superoxide production by the mitochondrial respiratory chain","volume":"17","author":"Turrens","year":"1997","journal-title":"Biosci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1111\/j.1471-4159.1992.tb10990.x","article-title":"Reactive Oxygen Species and the Central Nervous System","volume":"59","author":"Halliwell","year":"1992","journal-title":"J. Neurochem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"8010","DOI":"10.1073\/pnas.130135897","article-title":"Identification of Renox, an NAD(P)H oxidase in kidney","volume":"97","author":"Geiszt","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/43459","article-title":"Cell transformation by the superoxide-generating oxidase Mox1","volume":"401","author":"Suh","year":"1999","journal-title":"Nature"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s00423-006-0073-1","article-title":"Chronic inflammation and oxidative stress in the genesis and perpetuation of cancer: Role of lipid peroxidation, DNA damage, and repair","volume":"391","author":"Bartsch","year":"2006","journal-title":"Langenbeck\u2019s Arch. Surg."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1042\/bj1280617","article-title":"The cellular production of hydrogen peroxide","volume":"128","author":"Boveris","year":"1972","journal-title":"Biochem. J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1440-1746.2010.06592.x","article-title":"Reactive oxygen and mechanisms of inflammatory liver injury: Present concepts: Reactive oxygen and liver inflammation","volume":"26","author":"Jaeschke","year":"2011","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1016\/0006-2952(93)90201-7","article-title":"Oxidative stress in cultured hepatocytes exposed to acetaminophen","volume":"45","author":"Adamson","year":"1993","journal-title":"Biochem. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.tiv.2010.11.019","article-title":"Mitochondrial CYP2E1 is sufficient to mediate oxidative stress and cytotoxicity induced by ethanol and acetaminophen","volume":"25","author":"Knockaert","year":"2011","journal-title":"Toxicol. In Vitro"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0041-008X(03)00368-5","article-title":"Diclofenac-induced liver injury: A paradigm of idiosyncratic drug toxicity","volume":"192","author":"Boelsterli","year":"2003","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1016\/j.bcp.2003.08.003","article-title":"Diclofenac induces apoptosis in hepatocytes by alteration of mitochondrial function and generation of ROS","volume":"66","author":"Ponsoda","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.cbi.2009.11.024","article-title":"Salicylic acid-induced hepatotoxicity triggered by oxidative stress","volume":"183","author":"Doi","year":"2010","journal-title":"Chem. Biol. Interact."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0378-4274(99)00180-0","article-title":"Ibuprofen-induced liver mitochondrial permeability transition","volume":"111","year":"2000","journal-title":"Toxicol. Lett."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s00360-012-0652-0","article-title":"Coping with physiological oxidative stress: A review of antioxidant strategies in seals","volume":"182","author":"Elsner","year":"2012","journal-title":"J. Comp. Physiol. B"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1089\/ars.2006.8.1865","article-title":"Redefining oxidative stress","volume":"8","author":"Jones","year":"2006","journal-title":"Antioxid. Redox Signal."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.clinbiochem.2008.01.029","article-title":"Lipid, protein, DNA oxidation and antioxidant status in rheumatoid arthritis","volume":"41","author":"Seven","year":"2008","journal-title":"Clin. Biochem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0014-5793(94)01368-B","article-title":"Persistent oxidative stress in cancer","volume":"358","author":"Toyokuni","year":"1995","journal-title":"FEBS Lett."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.jhep.2005.07.034","article-title":"Superoxide anions and hydrogen peroxide induce hepatocyte death by different mechanisms: Involvement of JNK and ERK MAP kinases","volume":"44","author":"Schoemaker","year":"2006","journal-title":"J. Hepatol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.tips.2010.12.002","article-title":"Free radicals and antioxidants\u2014Quo vadis?","volume":"32","author":"Halliwell","year":"2011","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0300-483X(02)00448-1","article-title":"Oxy radicals, lipid peroxidation and DNA damage","volume":"181\u2013182","author":"Marnett","year":"2002","journal-title":"Toxicology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"875","DOI":"10.3892\/or.2013.2227","article-title":"Oxidative stress-induced 1, N6-ethenodeoxyadenosine adduct formation contributes to hepatocarcinogenesis","volume":"29","author":"Zhou","year":"2013","journal-title":"Oncol. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"5746","DOI":"10.1073\/pnas.100422497","article-title":"Protein oxidation in response to increased transcriptional or translational errors","volume":"97","author":"Dukan","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"11848","DOI":"10.1073\/pnas.93.21.11848","article-title":"Reactive oxygen species are downstream mediators of p53-dependent apoptosis","volume":"93","author":"Johnson","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/38525","article-title":"A model for p53-induced apoptosis","volume":"389","author":"Polyak","year":"1997","journal-title":"Nature"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"5314","DOI":"10.1002\/j.1460-2075.1996.tb00916.x","article-title":"Dephosphorylation of receptor tyrosine kinases as target of regulation by radiation, oxidants or alkylating agents","volume":"15","author":"Knebel","year":"1996","journal-title":"EMBO J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"14624","DOI":"10.1074\/jbc.275.19.14624","article-title":"Epidermal growth factor receptor-dependent Akt activation by oxidative stress enhances cell survival","volume":"275","author":"Wang","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1093\/emboj\/17.9.2596","article-title":"Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1","volume":"17","author":"Saitoh","year":"1998","journal-title":"EMBO J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1093\/emboj\/18.5.1321","article-title":"Regulation of JNK signaling by GSTp","volume":"18","author":"Adler","year":"1999","journal-title":"EMBO J."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"26087","DOI":"10.3390\/ijms161125942","article-title":"The Role of Oxidative Stress and Antioxidants in Liver Diseases","volume":"16","author":"Li","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"S44","DOI":"10.1086\/381446","article-title":"Drug-induced liver injury","volume":"38","author":"Kaplowitz","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1002\/hep.23937","article-title":"Drug-induced acute liver failure: Results of a U.S. Multicenter, prospective study","volume":"52","author":"Reuben","year":"2010","journal-title":"Hepatology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1002\/hep.20948","article-title":"Acetaminophen-induced acute liver failure: Results of a United States multicenter, prospective study","volume":"42","author":"Larson","year":"2005","journal-title":"Hepatology"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1056\/NEJMra1208937","article-title":"Acute Liver Failure","volume":"369","author":"Bernal","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"4865","DOI":"10.3748\/wjg.15.4865","article-title":"Biochemical mechanisms in drug-induced liver injury: Certainties and doubts","volume":"15","author":"Grattagliano","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Iorga, A., Dara, L., and Kaplowitz, N. (2017). Drug-Induced Liver Injury: Cascade of Events Leading to Cell Death, Apoptosis or Necrosis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18051018"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"9176937","DOI":"10.1155\/2017\/9176937","article-title":"Idiosyncratic Drug-Induced Liver Injury (IDILI): Potential Mechanisms and Predictive Assays","volume":"2017","author":"Roth","year":"2017","journal-title":"BioMed Res. Int."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.tips.2013.01.009","article-title":"Regulation of drug-induced liver injury by signal transduction pathways: Critical role of mitochondria","volume":"34","author":"Han","year":"2013","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/taap.1996.8074","article-title":"Selective Protein Covalent Binding and Target Organ Toxicity","volume":"143","author":"Cohen","year":"1997","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2133\/dmpk.DMPK-10-RV-089","article-title":"Role of biotransformation in drug-induced toxicity: Influence of intra-and inter-species differences in drug metabolism","volume":"26","author":"Baillie","year":"2011","journal-title":"Drug Metab. Pharmacokinet."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0168-8278(00)80414-6","article-title":"Mechanisms of liver cell injury","volume":"32","author":"Kaplowitz","year":"2000","journal-title":"J. Hepatol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1111\/j.1478-3231.2011.02604.x","article-title":"Antioxidants as therapeutic agents for liver disease","volume":"31","author":"Singal","year":"2011","journal-title":"Liver Int."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Uetrecht, J. (2010). Signal Transduction Pathways Involved in Drug-Induced Liver Injury. Adverse Drug Reactions, Springer. Available online: http:\/\/dx.doi.org\/10.1007\/978-3-642-00663-0_10.","DOI":"10.1007\/978-3-642-00663-0_10"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.jhep.2010.11.006","article-title":"Drug-induced toxicity on mitochondria and lipid metabolism: Mechanistic diversity and deleterious consequences for the liver","volume":"54","author":"Begriche","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.1016\/S0021-9258(18)34844-0","article-title":"Status of the mitochondrial pool of glutathione in the isolated hepatocyte","volume":"257","author":"Meredith","year":"1982","journal-title":"J. Biol. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1124\/mi.10.2.7","article-title":"Mechanisms of pathogenesis in drug hepatotoxicity putting the stress on mitochondria","volume":"10","author":"Jones","year":"2010","journal-title":"Mol. Interv."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Simon, L.S. (2013). Nonsteroidal anti-inflammatory drugs and their risk: A story still in development. BMC Arthritis Res. Ther., 15.","DOI":"10.1186\/ar4173"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"536962","DOI":"10.1155\/2015\/536962","article-title":"NSAIDs and Cardiovascular Diseases: Role of Reactive Oxygen Species","volume":"2015","author":"Ghosh","year":"2015","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1096\/fasebj.12.12.1063","article-title":"Cyclooxygenase in biology and disease","volume":"12","author":"Dubois","year":"1998","journal-title":"FASEB J."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Crofford, L.J. (2013). Use of NSAIDs in treating patients with arthritis. BMC Arthritis Res. Ther., 15.","DOI":"10.1186\/ar4174"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/liv.13032","article-title":"Liver injury from nonsteroidal anti-inflammatory drugs in the United States","volume":"36","author":"Schmeltzer","year":"2016","journal-title":"Liver Int."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.mayocp.2013.09.016","article-title":"Drug-Induced Liver Injury","volume":"89","author":"Leise","year":"2014","journal-title":"Mayo Clin. Proc."},{"key":"ref_126","first-page":"643","article-title":"Nonsteroidal Anti-Inflammatory Drug\u2013Induced Hepatoxicity","volume":"17","author":"Unzueta","year":"2013","journal-title":"Drug Hepatotoxic."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1124\/mol.108.049569","article-title":"Nonsteroidal Anti-Inflammatory Drugs Induced Endothelial Apoptosis by Perturbing Peroxisome Proliferator-Activated Receptor-\u03b4 Transcriptional Pathway","volume":"74","author":"Liou","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/0016-5085(95)90335-6","article-title":"Poly(adenosine diphosphate ribose) polymerase inhibition prevents necrosis induced by H2O2 but not apoptosis","volume":"109","author":"Watson","year":"1995","journal-title":"Gastroenterology"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.3109\/13880209.2016.1150302","article-title":"Role of food-derived antioxidant agents against acetaminophen-induced hepatotoxicity","volume":"54","year":"2016","journal-title":"Pharm. Biol."},{"key":"ref_130","first-page":"103","article-title":"Intoxicaci\u00f3n por acetaminof\u00e9n en adultos","volume":"33","author":"Castro","year":"2016","journal-title":"Med. Leg. Costa Rica"},{"key":"ref_131","first-page":"587","article-title":"Acetaminophen-related Hepatotoxicity","volume":"17","author":"Bunchorntavakul","year":"2013","journal-title":"Drug Hepatotoxic."},{"key":"ref_132","first-page":"499","article-title":"A Review of Acetaminophen Poisoning","volume":"28","author":"Hodgman","year":"2012","journal-title":"Toxicology"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1055\/s-0032-1301733","article-title":"Acute Liver Failure","volume":"33","author":"Lee","year":"2012","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1159\/000374090","article-title":"Acetaminophen: Dose-Dependent Drug Hepatotoxicity and Acute Liver Failure in Patients","volume":"33","author":"Jaeschke","year":"2015","journal-title":"Dig. Dis."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00204-014-1432-2","article-title":"Acetaminophen hepatotoxicity: An updated review","volume":"89","author":"Lancaster","year":"2015","journal-title":"Arch. Toxicol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0378-4274(03)00239-X","article-title":"The role of oxidant stress and reactive nitrogen species in acetaminophen hepatotoxicity","volume":"144","author":"Jaeschke","year":"2003","journal-title":"Toxicol. Lett."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1007\/s11095-013-1007-6","article-title":"Metabolism and Disposition of Acetaminophen: Recent Advances in Relation to Hepatotoxicity and Diagnosis","volume":"30","author":"McGill","year":"2013","journal-title":"Pharm. Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1002\/hep.26625","article-title":"Protein kinase C (PKC) participates in acetaminophen hepatotoxicity through JNK dependent and independent signaling pathways","volume":"59","author":"Saberi","year":"2014","journal-title":"Hepatology"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3109\/03602532.2011.602688","article-title":"Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: Lessons learned from acetaminophen hepatotoxicity","volume":"44","author":"Jaeschke","year":"2012","journal-title":"Drug Metab. Rev."},{"key":"ref_140","first-page":"153","article-title":"Acetaminophen-induced Liver Injury: From Animal Models to Humans","volume":"2","author":"Jaeschke","year":"2014","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1124\/jpet.105.088898","article-title":"Peroxynitrite-Induced Mitochondrial and Endonuclease-Mediated Nuclear DNA Damage in Acetaminophen Hepatotoxicity","volume":"315","author":"Cover","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jhep.2004.09.015","article-title":"Involvement of mitochondrial permeability transition in acetaminophen-induced liver injury in mice","volume":"42","author":"Masubuchi","year":"2005","journal-title":"J. Hepatol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"13565","DOI":"10.1074\/jbc.M708916200","article-title":"Role of JNK Translocation to Mitochondria Leading to Inhibition of Mitochondria Bioenergetics in Acetaminophen-induced Liver Injury","volume":"283","author":"Hanawa","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1093\/toxsci\/67.2.322","article-title":"Mode of Cell Death after Acetaminophen Overdose in Mice: Apoptosis or Oncotic Necrosis?","volume":"67","author":"Gujral","year":"2002","journal-title":"Toxicol. Sci."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"340","DOI":"10.3109\/10715760903513017","article-title":"Acetaminophen induced acute liver failure via oxidative stress and JNK activation: Protective role of taurine by the suppression of cytochrome P450 2E1","volume":"44","author":"Das","year":"2010","journal-title":"Free Radic. Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"389","DOI":"10.2220\/biomedres.35.389","article-title":"Acrolein, a highly toxic aldehyde generated under oxidative stress in vivo, aggravates the mouse liver damage after acetaminophen overdose","volume":"35","author":"Arai","year":"2014","journal-title":"Biomed. Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1002\/hep.20437","article-title":"Mitochondrial permeability transition in acetaminophen-induced necrosis and apoptosis of cultured mouse hepatocytes","volume":"40","author":"Kon","year":"2004","journal-title":"Hepatology"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1196\/annals.1299.103","article-title":"The Role of Apoptosis in Acetaminophen-Induced Injury","volume":"1010","author":"Kass","year":"2003","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1097\/CCM.0b013e31829791a2","article-title":"Character and Temporal Evolution of Apoptosis in Acetaminophen-Induced Acute Liver Failure","volume":"41","author":"Possamai","year":"2013","journal-title":"Crit. Care Med."},{"key":"ref_150","first-page":"131","article-title":"Acetaminophen-Induced Hepatotoxicity: A Comprehensive Update","volume":"4","author":"Yoon","year":"2016","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_151","first-page":"9","article-title":"Aspirin induced changes in serum ACP, ALP, GOT, GPT, bilirubin and creatinine in corelation with histopathological changes in liver and kidney of female albino rat","volume":"4","author":"Jain","year":"2012","journal-title":"Int. J. Appl. Pharm."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ejps.2015.03.015","article-title":"Aromatic Hydroxylation of Salicylic Acid and Aspirin by Human Cytochromes P450","volume":"73","author":"Sedgeman","year":"2015","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"103","DOI":"10.7326\/0003-4819-80-1-103","article-title":"Aspirin-induced hepatic injury","volume":"80","author":"Zimmerman","year":"1974","journal-title":"Ann. Intern. Med."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"5651","DOI":"10.3748\/wjg.v16.i45.5651","article-title":"Non-steroidal anti-inflammatory drugs: What is the actual risk of liver damage?","volume":"16","author":"Bessone","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_155","first-page":"265","article-title":"Salicylic acid-induced lipid peroxidation in rat liver microsomes","volume":"100","author":"Doi","year":"1998","journal-title":"Res. Commun. Mol. Pathol. Pharmacol."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Berk, M., Dean, O., Drexhage, H., McNeil, J.J., Moylan, S., O\u2019Neil, A., Davey, C., Sanna, L., and Maes, M. (2013). Aspirin: A review of its neurobiological properties and therapeutic potential for mental illness. BMC Med., 11.","DOI":"10.1186\/1741-7015-11-74"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ejphar.2011.06.016","article-title":"Acetylsalicylic acid-induced oxidative stress, cell cycle arrest, apoptosis and mitochondrial dysfunction in human hepatoma HepG2 cells","volume":"668","author":"Raza","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Raza, H., and John, A. (2012). Implications of Altered Glutathione Metabolism in Aspirin-Induced Oxidative Stress and Mitochondrial Dysfunction in HepG2 Cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036325"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00592-014-0629-4","article-title":"Low dose of acetylsalicylic acid and oxidative stress-mediated endothelial dysfunction in diabetes: A short-term evaluation","volume":"52","author":"Tassone","year":"2015","journal-title":"Acta Diabetol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/S0022-3565(25)20562-6","article-title":"Inhibition by salicylic acid of the activation and thus oxidation of long chain fatty acids. Possible role in the development of Reye\u2019s syndrome","volume":"259","author":"Deschamps","year":"1991","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_161","first-page":"378","article-title":"Noninvasive assessment of the effect of xenobiotics on mitochondrial function in human beings: Studies with acetylsalicylic acid and ethanol with the use of the carbon 13-labeled ketoisocaproate breath test","volume":"125","author":"Lauterburg","year":"1995","journal-title":"J. Lab. Clin. Med."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0163-7258(95)00012-6","article-title":"Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity","volume":"67","author":"Fromenty","year":"1995","journal-title":"Pharmacol. Ther."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1185\/03007995.2010.486301","article-title":"Diclofenac: An update on its mechanism of action and safety profile","volume":"26","author":"Gan","year":"2010","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1007\/s40265-015-0392-z","article-title":"Advances in NSAID Development: Evolution of Diclofenac Products Using Pharmaceutical Technology","volume":"75","author":"Altman","year":"2015","journal-title":"Drugs"},{"key":"ref_165","first-page":"563","article-title":"Nonsteroidal Anti-Inflammatory Drug\u2013Induced Hepatotoxicity","volume":"11","author":"Aithal","year":"2007","journal-title":"Drug Induc. Liver Dis."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1002\/hep.22633","article-title":"Using controlled clinical trials to learn more about acute drug-induced liver injury","volume":"48","author":"Watkins","year":"2008","journal-title":"Hepatology"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1002\/hep.1840220320","article-title":"Diclofenac-associated hepatotoxicity: Analysis of 180 cases reported to the food and drug administration as adverse reactions","volume":"22","author":"Banks","year":"1995","journal-title":"Hepatology"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/ajg.2008.149","article-title":"How Common Is Diclofenac-Associated Liver Injury? Analysis of 17,289 Arthritis Patients in a Long-Term Prospective Clinical Trial","volume":"104","author":"Laine","year":"2009","journal-title":"Am. J. Gastroenterol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.tox.2012.01.008","article-title":"Involvement of immune-related factors in diclofenac-induced acute liver injury in mice","volume":"293","author":"Yano","year":"2012","journal-title":"Toxicology"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0022-3565(24)37925-X","article-title":"Diclofenac Toxicity to Hepatocytes: A Role for Drug Metabolism in Cell Toxicity","volume":"288","author":"Bort","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.tox.2004.11.039","article-title":"Oxidative stress mediates drug-induced hepatotoxicity in rats: A possible role of DNA fragmentation","volume":"208","author":"Amin","year":"2005","journal-title":"Toxicology"},{"key":"ref_172","first-page":"9","article-title":"Tissue slices for the evaluation of metabolism-based toxicity with the example of diclofenac","volume":"179","author":"Vickers","year":"2009","journal-title":"Eval. Metab. Based Drug Toxic Drug Dev."},{"key":"ref_173","first-page":"877","article-title":"Involvement of Lysosomal Labilisation and Lysosomal\/mitochondrial Cross-Talk in Diclofenac Induced Hepatotoxicity","volume":"10","author":"Pourahmad","year":"2011","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1093\/toxsci\/kfu072","article-title":"Drug-Induced Endoplasmic Reticulum and Oxidative Stress Responses Independently Sensitize toward TNF\u03b1-Mediated Hepatotoxicity","volume":"140","author":"Fredriksson","year":"2014","journal-title":"Toxicol. Sci."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1136\/bmj.295.6591.180","article-title":"Cross hepatotoxicity between non-steroidal anti-inflammatory drugs","volume":"295","author":"Andrejak","year":"1987","journal-title":"Br. Med. J. Clin. Res. Ed."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/S1499-3872(11)60093-3","article-title":"Naproxen-induced liver injury","volume":"10","author":"Ali","year":"2011","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"268","DOI":"10.2165\/00003088-199732040-00002","article-title":"Clinical Pharmacokinetics of Naproxen","volume":"32","author":"Davies","year":"1997","journal-title":"Clin. Pharmacokinet."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/0006-2952(96)85085-4","article-title":"Cytochromes P450, 1A2, and 2C9 are responsible for the human hepatic O-demethylation of R- and S-naproxen","volume":"51","author":"Miners","year":"1996","journal-title":"Biochem. Pharmacol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s002280050293","article-title":"Involvement of multiple cytochrome P450 isoforms in naproxen O-demethylation","volume":"52","author":"Tracy","year":"1997","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/j.1365-2125.2005.02446.x","article-title":"S-Naproxen and desmethylnaproxen glucuronidation by human liver microsomes and recombinant human UDP-glucuronosyltransferases (UGT): Role of UGT2B7 in the elimination of naproxen","volume":"60","author":"Bowalgaha","year":"2005","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/0006-2952(94)00542-T","article-title":"Oxidative stress in isolated rat hepatocytes during naproxen metabolism","volume":"49","author":"Yokoyama","year":"1995","journal-title":"Biochem. Pharmacol."},{"key":"ref_182","first-page":"143","article-title":"Glutathione disulfide formation during naproxen metabolism in the isolated rat hepatocytes","volume":"99","author":"Yokoyama","year":"1998","journal-title":"Res. Commun. Mol. Pathol. Pharmacol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1600-0773.2001.890107.x","article-title":"A Possible Mechanism of Naproxen-Induced Lipid Peroxidation in Rat Liver Microsomes","volume":"89","author":"Ji","year":"2001","journal-title":"Pharmacol. Toxicol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1080\/00498250110052715","article-title":"Disposition of naproxen, naproxen acyl glucuronide and its rearrangement isomers in the isolated perfused rat liver","volume":"31","author":"Lo","year":"2001","journal-title":"Xenobiotica"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.cbi.2006.01.003","article-title":"Naproxen-induced oxidative stress in the isolated perfused rat liver","volume":"160","author":"Yokoyama","year":"2006","journal-title":"Chem. Biol. Interact."},{"key":"ref_186","unstructured":"(2017, June 27). Naproxen, Available online: https:\/\/livertox.nlm.nih.gov\/\/Naproxen.htm."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"155","DOI":"10.5001\/omj.2010.49","article-title":"An Overview of Clinical Pharmacology of Ibuprofen","volume":"25","author":"Bushra","year":"2010","journal-title":"Oman Med. J."},{"key":"ref_188","unstructured":"(2017, June 27). Ibuprofen. LiverTox, Available online: https:\/\/livertox.nlm.nih.gov\/\/Ibuprofen.htm."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s10787-009-0016-x","article-title":"Ibuprofen: Pharmacology, efficacy and safety","volume":"17","author":"Rainsford","year":"2009","journal-title":"Inflammopharmacology"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1111\/j.1572-0241.1998.00484.x","article-title":"Ibuprofen-induced hepatotoxicity in patients with chronic hepatitis c: A case series","volume":"93","author":"Riley","year":"1998","journal-title":"Am. J. Gastroenterol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.ajg.2016.08.006","article-title":"Acute vanishing bile duct syndrome after the use of ibuprofen","volume":"17","author":"Basturk","year":"2016","journal-title":"Arab. J. Gastroenterol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"4850","DOI":"10.2174\/092986712803341520","article-title":"Role of oxidative stress and molecular changes in liver fibrosis: A review","volume":"19","author":"Uribe","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1042\/BST0351147","article-title":"Biochemistry of oxidative stress","volume":"35","author":"Halliwell","year":"2007","journal-title":"Biochem. Soc. Trans."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0300-483X(00)00306-1","article-title":"Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology","volume":"153","year":"2000","journal-title":"Toxicology"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1089\/ars.2009.2634","article-title":"Redox control of liver function in health and disease","volume":"12","author":"Colell","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"191","DOI":"10.4161\/oxim.2.4.9112","article-title":"Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure","volume":"2","author":"Flora","year":"2009","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1128\/jb.117.2.456-460.1974","article-title":"Superoxide dismutase and oxygen toxicity in a eukaryote","volume":"117","author":"Gregory","year":"1974","journal-title":"J. Bacteriol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1089\/ars.2007.1908","article-title":"Extracellular Superoxide Dismutase in Pulmonary Fibrosis","volume":"10","author":"Gao","year":"2008","journal-title":"Antioxid. Redox Signal."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"6035","DOI":"10.3748\/wjg.v16.i48.6035","article-title":"Oxidative stress and antioxidants in hepatic pathogenesis","volume":"16","author":"Ha","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/S0009-9120(99)00075-2","article-title":"Antioxidant enzymes and human diseases","volume":"32","year":"1999","journal-title":"Clin. Biochem."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1016\/j.freeradbiomed.2005.02.026","article-title":"Peroxiredoxins: A historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling","volume":"38","author":"Rhee","year":"2005","journal-title":"Free Radic. Biol. Med."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1006\/geno.1996.0554","article-title":"Human thioredoxin reductase gene localization to chromosomal position 12q23\u2013q24.1 and mRNA distribution in human tissue","volume":"37","author":"Gasdaska","year":"1996","journal-title":"Genomics"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.taap.2004.10.001","article-title":"Hepatic mitochondrial glutathione: Transport and role in disease and toxicity","volume":"204","author":"Kaplowitz","year":"2005","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.jnutbio.2005.05.013","article-title":"Novel mechanisms of natural antioxidant compounds in biological systems: Involvement of glutathione and glutathione-related enzymes","volume":"16","author":"Masella","year":"2005","journal-title":"J. Nutr. Biochem."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.cell.2006.09.024","article-title":"Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC-1 Transcriptional Coactivators","volume":"127","author":"Drori","year":"2006","journal-title":"Cell"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"14476","DOI":"10.1074\/jbc.M807397200","article-title":"Mutual Dependence of Foxo3a and PGC-1\u03b1 in the Induction of Oxidative Stress Genes","volume":"284","author":"Olmos","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"9926","DOI":"10.1073\/pnas.91.21.9926","article-title":"Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2\/AP1 repeat of the beta-globin locus control region","volume":"91","author":"Moi","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.freeradbiomed.2009.07.035","article-title":"Nrf2:INrf2 (Keap1) signaling in oxidative stress","volume":"47","author":"Kaspar","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.freeradbiomed.2015.05.036","article-title":"Oxidative stress response and Nrf2 signaling in aging","volume":"88","author":"Zhang","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/bdd.680","article-title":"Nrf2 plays an important role in coordinated regulation of Phase II drug metabolism enzymes and Phase III drug transporters","volume":"30","author":"Shen","year":"2009","journal-title":"Biopharm. Drug Dispos."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1146\/annurev.pharmtox.43.100901.140229","article-title":"Regulatory mechanisms controlling gene expression mediated by the antioxidant response element","volume":"43","author":"Nguyen","year":"2003","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"11632","DOI":"10.1016\/S0021-9258(18)99004-6","article-title":"The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity","volume":"266","author":"Rushmore","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1007\/s00394-012-0380-y","article-title":"Critical review: Vegetables and fruit in the prevention of chronic diseases","volume":"51","author":"Boeing","year":"2012","journal-title":"Eur. J. Nutr."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.foodchem.2015.03.039","article-title":"Plant derived and dietary phenolic antioxidants: Anticancer properties","volume":"183","author":"Roleira","year":"2015","journal-title":"Food Chem."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1001\/jama.1996.03530300031036","article-title":"Vegetable, fruit, and cereal fiber intake and risk of coronary heart disease among men","volume":"275","author":"Rimm","year":"1996","journal-title":"JAMA"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"7792","DOI":"10.3390\/molecules15117792","article-title":"Nutraceutical Antioxidants as Novel Neuroprotective Agents","volume":"15","author":"Kelsey","year":"2010","journal-title":"Molecules"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.clnu.2013.03.011","article-title":"Dietary flavonoids intake and risk of type 2 diabetes: A meta-analysis of prospective cohort studies","volume":"33","author":"Liu","year":"2014","journal-title":"Clin. Nutr."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1093\/ije\/20.4.886","article-title":"Nutrient intakes and blood pressure in normotensive males","volume":"20","author":"Ascherio","year":"1991","journal-title":"Int. J. Epidemiol."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1093\/jnci\/66.6.1192","article-title":"The causes of cancer: Quantitative estimates of avoidable risks of cancer in the United States today","volume":"66","author":"Doll","year":"1981","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"7915","DOI":"10.1073\/pnas.90.17.7915","article-title":"Oxidants, antioxidants, and the degenerative diseases of aging","volume":"90","author":"Ames","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"5315","DOI":"10.1021\/jf0009293","article-title":"Phenol Antioxidant Quantity and Quality in Foods: Fruits","volume":"49","author":"Vinson","year":"2001","journal-title":"J. Agric. Food Chem."},{"key":"ref_222","first-page":"145","article-title":"Vegetables, fruits and phytoestrogens in the prevention of diseases","volume":"50","author":"Heber","year":"2004","journal-title":"J. Postgrad. Med."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1002\/anie.201000044","article-title":"Plant Polyphenols: Chemical Properties, Biological Activities, and Synthesis","volume":"50","author":"Quideau","year":"2011","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1080\/10408690091189257","article-title":"Natural pigments: Carotenoids, anthocyanins, and betalains\u2014Characteristics, biosynthesis, processing, and stability","volume":"40","year":"2000","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"9484","DOI":"10.1021\/jf801555q","article-title":"Influence of Processing on Quality Parameters of Strawberries","volume":"56","author":"Hartmann","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0378-8741(98)00131-7","article-title":"Antibacterial, antifungal and antiviral activity of propolis of different geographic origin","volume":"64","author":"Kujumgiev","year":"1999","journal-title":"J. Ethnopharmacol."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/1743-7075-8-73","article-title":"Chemopreventive effect of cactus Opuntia ficus indica on oxidative stress and genotoxicity of aflatoxin B1","volume":"8","author":"Brahmi","year":"2011","journal-title":"Nutr. Metabol."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1021\/jf0115589","article-title":"Thermal Processing Enhances the Nutritional Value of Tomatoes by Increasing Total Antioxidant Activity","volume":"50","author":"Dewanto","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S0031-9422(00)00235-1","article-title":"Advances in flavonoid research since 1992","volume":"55","author":"Harborne","year":"2000","journal-title":"Phytochemistry"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1093\/aob\/mcr234","article-title":"Flavonols: Old compounds for old roles","volume":"108","author":"Pollastri","year":"2011","journal-title":"Ann. Bot."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/0076-6879(94)34111-7","article-title":"Naturally occurring flavonoids: Structure, chemistry, and high-performance liquid chromatography methods for separation and characterization","volume":"234","author":"Das","year":"1994","journal-title":"Oxyg. Radic. Biol. Syst. Part D"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0163-7258(02)00298-X","article-title":"The biochemistry and medical significance of the flavonoids","volume":"96","author":"Havsteen","year":"2002","journal-title":"Pharmacol. Ther."},{"key":"ref_233","first-page":"222","article-title":"Flavonoids: Biosynthesis, biological functions, and biotechnological applications","volume":"3","author":"Rius","year":"2012","journal-title":"Front. Plant. Sci."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.phytochem.2010.04.016","article-title":"Multifunctional flavonoid dioxygenases: Flavonol and anthocyanin biosynthesis in Arabidopsis thaliana L.","volume":"71","author":"Martens","year":"2010","journal-title":"Phytochemistry"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/S0955-2863(02)00208-5","article-title":"Flavonoid antioxidants: Chemistry, metabolism and structure-activity relationships","volume":"13","author":"Heim","year":"2002","journal-title":"J. Nutr. Biochem."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/j.1749-6632.1998.tb09922.x","article-title":"The chemistry and biological effects of flavonoids and phenolic acids","volume":"854","author":"Croft","year":"1998","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1054\/mehy.1997.0686","article-title":"Flavonoids and tannins: Plant-based antioxidants with vitamin character","volume":"52","author":"Linag","year":"1999","journal-title":"Med. Hypotheses."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.1002\/jssc.200700261","article-title":"Extraction, separation, and detection methods for phenolic acids and flavonoids","volume":"30","author":"Stalikas","year":"2007","journal-title":"J. Sep. Sci."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"162750","DOI":"10.1155\/2013\/162750","article-title":"Chemistry and Biological Activities of Flavonoids: An Overview","volume":"2013","author":"Kumar","year":"2013","journal-title":"Sci. World J."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1159\/000399407","article-title":"The flavonoids. A class of semi-essential food components: Their role in human nutrition","volume":"24","year":"1976","journal-title":"Word Rew. Nutr. Diet."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1080\/01635589309514267","article-title":"Intake of potentially anticarcinogenic flavonoids and their determinants in adults in the Netherlands","volume":"20","author":"Hertog","year":"1993","journal-title":"Nutr. Cancer"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1001\/archinte.1995.00430040053006","article-title":"Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study","volume":"155","author":"Hertog","year":"1995","journal-title":"Arch. Intern. Med."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1021\/jf960339y","article-title":"Quantitative analysis of the flavonoid content of commercial tomatoes, onions, lettuce, and celery","volume":"45","author":"Crozier","year":"1997","journal-title":"J. Agric. Food Chem."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1021\/jf00032a015","article-title":"Content of potentially anticarcinogenic flavonoids of tea infusions, wines, and fruit juices","volume":"41","author":"Hertog","year":"1993","journal-title":"J. Agric. Food Chem."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.fct.2017.10.039","article-title":"Flavonoids as detoxifying and pro-survival agents: What\u2019s new?","volume":"110","author":"Dadar","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"ref_246","first-page":"659","article-title":"Phase I clinical trial of the flavonoid quercetin: Pharmacokinetics and evidence for in vivo tyrosine kinase inhibition","volume":"2","author":"Ferry","year":"1996","journal-title":"Clin. Cancer Res."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s00011-009-0037-3","article-title":"Flavonoids as anti-inflammatory agents: Implications in cancer and cardiovascular disease","volume":"58","author":"Villares","year":"2009","journal-title":"Inflamm. Res."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/0076-6879(90)86128-I","article-title":"Flavonoids as antioxidants: Determination of radical-scavenging efficiencies","volume":"186","author":"Bors","year":"1990","journal-title":"Oxyg. Radic. Biol. Syst. Part B Oxyg. Radic. Antioxid."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1021\/tx9600964","article-title":"A quantum chemical explanation of the antioxidant activity of flavonoids","volume":"9","author":"Tromp","year":"1996","journal-title":"Chem. Res. Toxicol."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"391","DOI":"10.3390\/nu6010391","article-title":"Recent Advances and Uses of Grape Flavonoids as Nutraceuticals","volume":"6","author":"Georgiev","year":"2014","journal-title":"Nutrients"},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1038\/aps.2012.62","article-title":"Differential hepatoprotective mechanisms of rutin and quercetin in CCl4-intoxicated BALB\/cN mice","volume":"33","author":"Jakovac","year":"2012","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.alcohol.2012.10.006","article-title":"Bilirubin participates in protecting of heme oxygenase-1 induction by quercetin against ethanol hepatotoxicity in cultured rat hepatocytes","volume":"47","author":"Jie","year":"2013","journal-title":"Alcohol"},{"key":"ref_253","doi-asserted-by":"crossref","unstructured":"Ji, L., Ma, Y., Wang, Z., Cai, Z., Pang, C., and Wang, Z. (2014). Quercetin Prevents Pyrrolizidine Alkaloid Clivorine-Induced Liver Injury in Mice by Elevating Body Defense Capacity. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098970"},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1177\/0192623311418680","article-title":"Role of Quercetin in Preventing Thioacetamide-Induced Liver Injury in Rats","volume":"39","author":"Rodrigues","year":"2011","journal-title":"Toxicol. Pathol."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.1016\/j.fct.2010.08.034","article-title":"Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat","volume":"48","author":"Yousef","year":"2010","journal-title":"Food Chem. Toxicol."},{"key":"ref_256","doi-asserted-by":"crossref","unstructured":"Babenko, N.A., and Shakhova, E.G. (2008). Effects of flavonoids on sphingolipid turnover in the toxin-damaged liver and liver cells. Lipids Health Dis., 7.","DOI":"10.1186\/1476-511X-7-1"},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s11373-006-9081-y","article-title":"Hepatoprotective effect of total flavonoids from Laggera alata against carbon tetrachloride-induced injury in primary cultured neonatal rat hepatocytes and in rats with hepatic damage","volume":"13","author":"Wu","year":"2006","journal-title":"J. Biomed. Sci."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.freeradbiomed.2011.10.483","article-title":"The anthocyanin cyanidin-3-O-\u03b2-glucoside, a flavonoid, increases hepatic glutathione synthesis and protects hepatocytes against reactive oxygen species during hyperglycemia: Involvement of a cAMP-PKA-dependent signaling pathway","volume":"52","author":"Zhu","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.etap.2016.07.014","article-title":"Zidovudine and isoniazid induced liver toxicity and oxidative stress: Evaluation of mitigating properties of silibinin","volume":"46","author":"Raghu","year":"2016","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0031-9422(02)00564-2","article-title":"Recent advances in betalain research","volume":"62","author":"Strack","year":"2003","journal-title":"Phytochemistry"},{"key":"ref_261","doi-asserted-by":"crossref","unstructured":"Hendry, G.A.F., and Houghton, J.D. (1996). Anthocyanins and betalains. Natural Food Colorants, Springer. Available online: http:\/\/dx.doi.org\/10.1007\/978-1-4615-2155-6_8.","DOI":"10.1007\/978-1-4615-2155-6_8"},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1021\/jf011305f","article-title":"Identification of Betalains from Yellow Beet (Beta vulgaris L.) and Cactus Pear [Opuntia ficus-indica (L.) Mill.] by High-Performance Liquid Chromatography\u2212Electrospray Ionization Mass Spectrometry","volume":"50","author":"Stintzing","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0099-9598(08)60163-7","article-title":"Chapter 1 Betalains","volume":"39","author":"Steglich","year":"1990","journal-title":"Alkaloids Chem. Pharmacol."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/0168-9452(94)90244-5","article-title":"Anthocyanins and betalains: Evolution of the mutually exclusive pathways","volume":"101","author":"Stafford","year":"1994","journal-title":"Plant Sci."},{"key":"ref_265","first-page":"360","article-title":"Pigment evolution in the Caryophyllales: A systematic overview","volume":"109","author":"Clement","year":"1996","journal-title":"Plant Biol."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"5178","DOI":"10.1021\/jf010456f","article-title":"Betalains. A New Class of Dietary Cationized Antioxidants","volume":"49","author":"Kanner","year":"2001","journal-title":"J. Agric. Food Chem."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1080\/02652030600986032","article-title":"Betanin, the main pigment of red beet: Molecular origin of its exceptionally high free radical-scavenging activity","volume":"23","author":"Szymusiak","year":"2006","journal-title":"Food Addit. Contam."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/(SICI)1099-1565(199805\/06)9:3<124::AID-PCA401>3.0.CO;2-0","article-title":"Characterization of the antiradical activity of betalains from Beta vulgaris L. roots","volume":"9","author":"Escribano","year":"1998","journal-title":"Phytochem. Anal."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"6895","DOI":"10.1021\/jf025696p","article-title":"Antioxidant Activities of Sicilian Prickly Pear (Opuntia ficus indica) Fruit Extracts and Reducing Properties of Its Betalains: Betanin and Indicaxanthin","volume":"50","author":"Butera","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s11130-005-5098-z","article-title":"Radical Scavenging Activity and Stability of Betalains from Beta vulgaris Hairy Root Culture in Simulated Conditions of Human Gastrointestinal Tract","volume":"60","author":"Pavlov","year":"2005","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"4382","DOI":"10.1016\/j.foodchem.2013.06.108","article-title":"Characterisation and determination of in vitro antioxidant potential of betalains from Talinum triangulare (Jacq.) Willd","volume":"141","author":"Swarna","year":"2013","journal-title":"Food Chem."},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.fct.2014.08.007","article-title":"Free radical scavenging and antioxidant activity of betanin: Electron spin resonance spectroscopy studies and studies in cultured cells","volume":"73","author":"Esatbeyoglu","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1017\/S0007114513001645","article-title":"Betanin, a beetroot component, induces nuclear factor erythroid-2-related factor 2-mediated expression of detoxifying\/antioxidant enzymes in human liver cell lines","volume":"110","author":"Paluszczak","year":"2013","journal-title":"Br. J. Nutr."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s11101-007-9084-y","article-title":"Betalains in the era of global agri-food science, technology and nutritional health","volume":"7","author":"Moreno","year":"2008","journal-title":"Phytochem. Rev."},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"6086","DOI":"10.1021\/jf020145k","article-title":"Fruit Flesh Betacyanin Pigments in Hylocereus Cacti","volume":"50","author":"Wybraniec","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.foodchem.2005.01.002","article-title":"Antioxidant and antiproliferative activities of red pitaya","volume":"95","author":"Wu","year":"2006","journal-title":"Food Chem."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.lwt.2012.01.025","article-title":"Pigment identification, nutritional composition, bioactivity, and in vitro cancer cell cytotoxicity of Rivina humilis L. berries, potential source of betalains","volume":"47","author":"Khan","year":"2012","journal-title":"LWT Food Sci. Technol."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1007\/s10695-013-9892-5","article-title":"Betanin attenuates carbon tetrachloride (CCl4)-induced liver injury in common carp (Cyprinus carpio L.)","volume":"40","author":"Han","year":"2014","journal-title":"Fish Physiol. Biochem."},{"key":"ref_279","doi-asserted-by":"crossref","unstructured":"Britton, G., Liaaen-Jensen, S., and Pfander, H. (2004). Introduction and guidelines on the use of the Handbook. Carotenoids: Handbook, Birkh\u00e4user Basel. Available online: http:\/\/dx.doi.org\/10.1007\/978-3-0348-7836-4_1.","DOI":"10.1007\/978-3-0348-7836-4_1"},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.plipres.2003.10.002","article-title":"The biosynthesis and nutritional uses of carotenoids","volume":"43","author":"Fraser","year":"2004","journal-title":"Prog. Lipid Res."},{"key":"ref_281","doi-asserted-by":"crossref","unstructured":"Stange, C. (2016). Carotenoids in Nature, Springer International Publishing. Available online: http:\/\/link.springer.com\/10.1007\/978-3-319-39126-7.","DOI":"10.1007\/978-3-319-39126-7"},{"key":"ref_282","doi-asserted-by":"crossref","unstructured":"Goodwin, T.W. (1980). Nature and Properties. The Biochemistry of the Carotenoids: Volume I Plants, Springer. Available online: http:\/\/dx.doi.org\/10.1007\/978-94-009-5860-9_1.","DOI":"10.1007\/978-94-009-5860-9_1"},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1096\/fasebj.9.15.8529834","article-title":"Structure and properties of carotenoids in relation to function","volume":"9","author":"Britton","year":"1995","journal-title":"FASEB J."},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/0076-6879(87)48036-1","article-title":"Chlorophylls and carotenoids: Pigments of photosynthetic biomembranes","volume":"148","author":"Lichtenthaler","year":"1987","journal-title":"Plant Cell Membr."},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0065-2296(08)60270-0","article-title":"Control of Isoprenoid Biosynthesis in Higher Plants","volume":"14","author":"Gray","year":"1988","journal-title":"Adv. Bot. Res."},{"key":"ref_286","first-page":"1015","article-title":"Terpenoid metabolism","volume":"7","author":"McGarvey","year":"1995","journal-title":"Plant Cell"},{"key":"ref_287","doi-asserted-by":"crossref","unstructured":"Goodwin, T.W. (1984). Mammals. The Biochemistry of the Carotenoids: Volume II Animals Goodwin, Springer. Available online: http:\/\/dx.doi.org\/10.1007\/978-94-009-5542-4_11.","DOI":"10.1007\/978-94-009-5542-4_11"},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"466","DOI":"10.3390\/nu6020466","article-title":"Potential Role of Carotenoids as Antioxidants in Human Health and Disease","volume":"6","author":"Fiedor","year":"2014","journal-title":"Nutrients"},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1079\/BJN2000284","article-title":"A European carotenoid database to assess carotenoid intakes and its use in a five-country comparative study","volume":"85","author":"Carroll","year":"2001","journal-title":"Br. J. Nutr."},{"key":"ref_290","doi-asserted-by":"crossref","unstructured":"Stange, C. (2016). Carotenoids as a Source of Antioxidants in the Diet. Carotenoids in Nature: Biosynthesis, Regulation and Function, Springer International Publishing. Available online: http:\/\/dx.doi.org\/10.1007\/978-3-319-39126-7_14.","DOI":"10.1007\/978-3-319-39126-7"},{"key":"ref_291","doi-asserted-by":"crossref","unstructured":"Bramley, P. (2003). The genetic enhancement of phytochemicals: The case of carotenoids. Phytochemical Functional Foods, Woodhead Publishing. Available online: http:\/\/www.sciencedirect.com\/science\/article\/pii\/B9781855736726500174.","DOI":"10.1533\/9781855736986.2.253"},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/0076-6879(92)13142-K","article-title":"Antioxidant effects of carotenoids in vivo and in vitro: An overview","volume":"213","author":"Palozza","year":"1992","journal-title":"Methods Enzymol."},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/j.1749-6632.1993.tb26154.x","article-title":"Antioxidant Reactions of Carotenoids","volume":"691","author":"Liebler","year":"1993","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_294","doi-asserted-by":"crossref","unstructured":"Ni, Y., Zhuge, F., Nagashimada, M., and Ota, T. (2016). Novel Action of Carotenoids on Non-Alcoholic Fatty Liver Disease: Macrophage Polarization and Liver Homeostasis. Nutrients, 8.","DOI":"10.3390\/nu8070391"},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1126\/science.278.5340.1073","article-title":"Recent Advances in Chemoprevention of Cancer","volume":"278","author":"Hong","year":"1997","journal-title":"Science"},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/0717-6287-47-49","article-title":"Protective effect of bixin on carbon tetrachloride-induced hepatotoxicity in rats","volume":"47","author":"Moreira","year":"2014","journal-title":"Biol. Res."},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"6703","DOI":"10.1007\/s13197-015-1775-6","article-title":"Evaluation of hepatoprotective and antioxidant activity of astaxanthin and astaxanthin esters from microalga-Haematococcus pluvialis","volume":"52","author":"Rao","year":"2015","journal-title":"J. Food Sci. Technol."},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1007\/s13105-014-0367-7","article-title":"Antioxidant effect of lycopene-enriched tomato paste on N-nitrosodiethylamine-induced oxidative stress in rats","volume":"70","author":"Kujawska","year":"2014","journal-title":"J. Physiol. Biochem."},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"10180","DOI":"10.3748\/wjg.v22.i46.10180","article-title":"Hepatoprotective and antioxidant effects of lycopene on non-alcoholic fatty liver disease in rat","volume":"22","author":"Jiang","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/S2221-1691(13)60009-X","article-title":"Lycopene stabilizes lipoprotein levels during d-galactosamine\/lipopolysaccharide induced hepatitis in experimental rats","volume":"2","author":"Sheriff","year":"2012","journal-title":"Asian Pac. J. Trop. Biomed."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/2\/117\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:52:26Z","timestamp":1760194346000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/2\/117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,24]]},"references-count":300,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2018,2]]}},"alternative-id":["nu10020117"],"URL":"https:\/\/doi.org\/10.3390\/nu10020117","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,24]]}}}