{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:21:57Z","timestamp":1790684517498,"version":"4.1.0"},"reference-count":77,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T00:00:00Z","timestamp":1570147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>This study examined the hepatoprotective and anti-inflammatory effects of anthocyanins from Vaccinim myrtillus (bilberry) fruit extract on the acute liver failure caused by carbon tetrachloride-CCl4 (3 mL\/kg, i.p.). The preventive treatment of the bilberry extract (200 mg anthocyanins\/kg, orally, 7 days) prior to the exposure to the CCl4 resulted in an evident decrease in markers of liver damage (glutamate dehydrogenase, sorbitol dehydrogenase, malate dehydrogenase), and reduced pro-oxidative (conjugated dienes, lipid hydroperoxide, thiobarbituric acid reactive substances, advanced oxidation protein products, NADPH oxidase, hydrogen peroxide, oxidized glutathione), and pro-inflammatory markers (tumor necrosis factor-alpha, interleukin-6, nitrite, myeloperoxidase, inducible nitric oxide synthase, cyclooxygenase-2, CD68, lipocalin-2), and also caused a significant decrease in the dissipation of the liver antioxidative defence capacities (reduced glutathione, glutathione S-transferase, and quinone reductase) in comparison to the results detected in the animals treated with CCl4 exclusively. The administration of the anthocyanins prevented the arginine metabolism\u2019s diversion towards the citrulline, decreased the catabolism of polyamines (the activity of putrescine oxidase and spermine oxidase), and significantly reduced the excessive activation and hyperplasia of the Kupffer cells. There was also an absence of necrosis, in regard to the toxic effect of CCl4 alone. The hepatoprotective mechanisms of bilberry extract are based on the inhibition of pro-oxidative mediators, strong anti-inflammatory properties, inducing of hepatic phase II antioxidant enzymes (glutathione S-transferase, quinone reductase) and reduced glutathione, hypoplasia of Kupffer cells, and a decrease in the catabolism of polyamines.<\/jats:p>","DOI":"10.3390\/antiox8100451","type":"journal-article","created":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T10:54:58Z","timestamp":1570186498000},"page":"451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Anthocyanins Protect Hepatocytes against CCl4-Induced Acute Liver Injury in Rats by Inhibiting Pro-inflammatory mediators, Polyamine Catabolism, Lipocalin-2, and Excessive Proliferation of Kupffer Cells"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9871-2804","authenticated-orcid":false,"given":"Dejan","family":"Popovi\u0107","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, University of Ni\u0161, Bulevar dr Zorana \u0110in\u0111i\u0107a 81, 18000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordana","family":"Koci\u0107","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, University of Ni\u0161, Bulevar dr Zorana \u0110in\u0111i\u0107a 81, 18000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vuka","family":"Kati\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, University of Ni\u0161, Bulevar dr Zorana \u0110in\u0111i\u0107a 81, 18000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Zarubica","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science and Mathematics, University of Ni\u0161, Vi\u0161egradska 33, 18000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ljubinka","family":"Jankovi\u0107 Veli\u010dkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, University of Ni\u0161, Bulevar dr Zorana \u0110in\u0111i\u0107a 81, 18000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanja P.","family":"Ni\u010dkovi\u0107","sequence":"additional","affiliation":[{"name":"Clinical-Hospital Center Pri\u0161tina, 38205 Gra\u010danica, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrija","family":"Jovi\u0107","sequence":"additional","affiliation":[{"name":"Clinic of Skin and Venereal Diseases, Clinical 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Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/j.1365-2613.2008.00576.x","article-title":"Single dose intravenous thioacetamide administration as a model of acute liver damage in rats","volume":"89","author":"Chen","year":"2008","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.fct.2012.11.022","article-title":"Antioxidant and hepatoprotective effects of Schisandra chinensis pollen extract on CCl4-induced acute liver damage in mice","volume":"55","author":"Cheng","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.aquaculture.2018.07.026","article-title":"Oxidative stress and inflammatory responses in the liver of swamp eel (Monopterus albus) exposed to carbon tetrachloride","volume":"496","author":"Liang","year":"2018","journal-title":"Aquaculture"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.cbi.2016.05.037","article-title":"Hepatoprotective effects of allyl isothiocyanate against carbon tetrachloride-induced hepatotoxicity in rat","volume":"254","author":"Ahn","year":"2016","journal-title":"Chem. Biol. Interact."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.toxrep.2015.05.012","article-title":"A single acute hepatotoxic dose of CCl4 causes oxidative stress in the rat brain","volume":"2","author":"Ritesh","year":"2015","journal-title":"Toxicol. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1016\/j.fct.2008.04.025","article-title":"Multiple treatment of propolis extract ameliorates carbon tetrachloride induced liver injury in rats","volume":"46","author":"Bhadauria","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.foodchem.2006.02.038","article-title":"Cytoprotective effect of a bilberry extract against oxidative damage of rat hepatocytes","volume":"101","author":"Cvak","year":"2007","journal-title":"Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6998","DOI":"10.1021\/jf200765n","article-title":"Phenolics in Slovenian bilberries (Vaccinium myrtillus L.) and blueberries (Vaccinium corymbosum L.)","volume":"59","author":"Polak","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.lfs.2016.06.007","article-title":"Antioxidant and proapoptotic effects of anthocyanins from bilberry extract in rats exposed to hepatotoxic effects of carbon tetrachloride","volume":"157","author":"Ulrih","year":"2016","journal-title":"Life Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Szymanowska, U., and Baraniak, B. (2019). Antioxidant and Potentially Anti-Inflammatory Activity of Anthocyanin Fractions from Pomace Obtained from Enzymatically Treated Raspberries. Antioxidants, 8.","DOI":"10.3390\/antiox8080299"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.fct.2016.09.009","article-title":"Pequi (Caryocar brasiliense Camb.) almond oil attenuates carbon tetrachloride-induced acute hepatic injury in rats: Antioxidant and anti-inflammatory effects","volume":"97","author":"Torres","year":"2016","journal-title":"Food Chem. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.jhep.2010.04.017","article-title":"Early growth response-1 attenuates liver injury and promotes hepatoprotection after carbon tetrachloride exposure in mice","volume":"53","author":"Pritchard","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"430","DOI":"10.3389\/fphys.2016.00430","article-title":"Lipocalin2 (LCN2) Expression in Hepatic Malfunction and Therapy","volume":"7","author":"Asimakopoulou","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Smirnova, O.A., Bartosch, B., Zakirova, N.F., Kochetkov, S.N., and Ivanov, A.V. (2018). Polyamine Metabolism and Oxidative Protein Folding in the ER as ROS-Producing Systems Neglected in Virology. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041219"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.cbi.2019.02.022","article-title":"Protective effects of anthocyanins from bilberry extract in rats exposed to nephrotoxic effects of carbon tetrachloride","volume":"304","author":"Zarubica","year":"2019","journal-title":"Chem. Biol. Interact."},{"key":"ref_17","first-page":"428","article-title":"Purification and some properties of glutamate dehydrogenase from Proteus inconstans","volume":"57","author":"Shimizu","year":"1979","journal-title":"J. Ferment. Technol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1093\/clinchem\/21.11.1619","article-title":"Reaction-rate assay of serum sorbitol dehydrogenase activity at 37 C","volume":"21","author":"Rose","year":"1975","journal-title":"Clin. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/j.1432-1033.1991.tb16291.x","article-title":"Malic enzyme in human liver Intracellular distribution, purification and properties of cytosolic isozyme","volume":"201","year":"1991","journal-title":"Eur. J. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.clinbiochem.2005.08.008","article-title":"A new automated colorimetric method for measuring total oxidant status","volume":"38","author":"Erel","year":"2005","journal-title":"Clin. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.clinbiochem.2003.11.015","article-title":"A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation","volume":"37","author":"Erel","year":"2004","journal-title":"Clin. Biochem."},{"key":"ref_22","first-page":"300","article-title":"Methods for estimating lipid peroxidation: An analysis of merits and demerits","volume":"40","author":"Devasagayam","year":"2003","journal-title":"Indian J. Biochem. Biophys."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0891-5849(95)00020-X","article-title":"Quantification of lipid peroxidation in tissue extracts based on Fe(III)xylenol orange complex formation","volume":"19","author":"Willmore","year":"1995","journal-title":"Free Radic. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sahreen, S., Khan, M.R., and Khan, R.A. (2011). Hepatoprotective effects of methanol extract of Carissa opaca leaves on CCl4-induced damage in rat. BMC Complement. Altern. Med., 11.","DOI":"10.1186\/1472-6882-11-48"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2524","DOI":"10.4049\/jimmunol.161.5.2524","article-title":"Advanced Oxidation Protein Products as Novel Mediators of Inflammation and Monocyte Activation in Chronic Renal Failure","volume":"161","author":"Friedlander","year":"1998","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0022-1759(80)90340-3","article-title":"A simple colorimetric method for the measurement of hydrogen peroxide produced by cells in culture","volume":"38","author":"Pick","year":"1980","journal-title":"J. Immunol. Methods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1007\/s00425-002-0829-y","article-title":"Involvement of plasma-membrane NADPH oxidase in abscisic acid-and water stress-induced antioxidant defense in leaves of maize seedlings","volume":"215","author":"Jiang","year":"2002","journal-title":"Planta"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.1038\/nprot.2006.378","article-title":"Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method","volume":"1","author":"Rahman","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sajid, M., Khan, M.R., Shah, N.A., Ullah, S., Younis, T., Majid, M., Ahmad, B., and Nigussie, D. (2016). Proficiencies of Artemisia Scoparia against CCl4 induced DNA damages and renal toxicity in rat. BMC Complement. Altern. Med., 16.","DOI":"10.1186\/s12906-016-1137-6"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/0003-9861(72)90164-6","article-title":"Guinea pig heterophil and eosinophil peroxidase","volume":"148","author":"Desser","year":"1972","journal-title":"Arch.Biochem. Biophys."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/0009-8981(75)90078-9","article-title":"Early diagnosis of myocardial infarction by arginase activity determination","volume":"60","author":"Porembska","year":"1975","journal-title":"Clin. Chim. Acta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1006\/abio.2000.4805","article-title":"A Colorimetric 96-Well Microtiter Plate Assay for the Determination of Enzymatically Formed Citrulline","volume":"286","author":"Knipp","year":"2000","journal-title":"Anal. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/0014-4827(72)90441-7","article-title":"Antipolyamine antibodies and cell lysis: The Inhibitory Effect of Putrescine","volume":"75","author":"Quash","year":"1972","journal-title":"Exp. Cell Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/0003-2697(77)90169-5","article-title":"Purification of glutathione S-transferases from human liver by glutathione-affinity chromatography","volume":"82","author":"Simons","year":"1977","journal-title":"Anal. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3109\/13880209.2014.909502","article-title":"Antioxidative and chemopreventive effects of Nephrolepis biserrata against carbon tetrachloride (CCl4)-induced oxidative stress and hepatic dysfunction in rats","volume":"53","author":"Shah","year":"2015","journal-title":"Pharm. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.etp.2011.06.003","article-title":"Chlorella vulgaris extract ameliorates carbon tetrachloride-induced acute hepatic injury in mice","volume":"65","author":"Li","year":"2013","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.fct.2017.12.020","article-title":"In vitro\/in vivo antioxidant and hepatoprotective potential of defatted extract and flavonoids isolated from Astragalus spruneri Boiss. (Fabaceae)","volume":"111","author":"Shkondrov","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.cbi.2015.01.030","article-title":"Myricitrin exhibits antioxidant, anti-inflammatory and antifibrotic activity in carbon tetrachloride-intoxicated mice","volume":"230","author":"Rashed","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cbi.2017.03.014","article-title":"The involvement of sirtuin 1 and heme oxygenase 1 in the hepatoprotective effects of quercetin against carbon tetrachloride-induced sub-chronic liver toxicity in rats","volume":"269","author":"Kemelo","year":"2017","journal-title":"Chem. Biol. Interact."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.toxlet.2008.04.012","article-title":"Up-regulation of hepatic heme oxygenase-1 expression by locally induced interleukin-6 in rats administered carbon tetrachloride intraperitoneally","volume":"179","author":"Yamaji","year":"2008","journal-title":"Toxicol. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.fct.2014.06.017","article-title":"Puerarin ameliorates carbon tetrachloride-induced oxidative DNA damage and inflammation in mouse kidney through ERK\/Nrf2\/ARE pathway","volume":"71","author":"Ma","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"\u017bebrowska, E., Maciejczyk, M., \u017bendzian-Piotrowska, M., Zalewska, A., and Chabowski, A. (2019). High Protein Diet Induces Oxidative Stress in Rat Cerebral Cortex and Hypothalamus. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071547"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"35523","DOI":"10.1074\/jbc.M111548200","article-title":"Distinct roles for glutathione S-transferases in the oxidative stress response in Schizosaccharomyces pombe","volume":"277","author":"Veal","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6475624","DOI":"10.1155\/2016\/6475624","article-title":"Polyphenols as Modulator of Oxidative Stress in Cancer Disease: New Therapeutic Strategies","volume":"2016","author":"Mileo","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_45","first-page":"15","article-title":"Phenylpropanoids as naturally occurring antioxidants: From plant defense to human health","volume":"53","author":"Korkina","year":"2007","journal-title":"Cell. Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1002\/biot.200600004","article-title":"An anthocyanin\/polyphenolic-rich fruit juice reduces oxidative DNA damage and increases glutathione level in healthy probands","volume":"1","author":"Weisel","year":"2006","journal-title":"Biotechnol. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/labinvest.2011.193","article-title":"Carbon tetrachloride-mediated lipid peroxidation induces early mitochondrial alterations in mouse liver","volume":"92","author":"Knockaert","year":"2012","journal-title":"Lab. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.etap.2017.06.026","article-title":"Protective effect of ferulic acid on cisplatin induced nephrotoxicity in rats","volume":"54","author":"Bami","year":"2017","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0378-4274(98)00110-6","article-title":"Serum and liver concentrations of tumor necrosis factor \u03b1 and interleukin-1\u03b2 following administration of carbon tetrachloride to male rats","volume":"98","author":"DeCicco","year":"1998","journal-title":"Toxicol. Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/0378-4274(83)90054-1","article-title":"Carbon tetrachloride (CCl4) levels and serum activities of liver enzymes following acute CCl4 intoxication","volume":"17","author":"Teschke","year":"1983","journal-title":"Toxicol. Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1093\/toxsci\/kft009","article-title":"Assessment of Emerging Biomarkers of Liver Injury in Human Subjects","volume":"132","author":"Schomaker","year":"2013","journal-title":"Toxicol. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.tox.2007.11.021","article-title":"The current state of serum biomarkers of hepatotoxicity","volume":"245","author":"Ozer","year":"2008","journal-title":"Toxicology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.foodchem.2012.10.026","article-title":"Hepatoprotective effect of 2,3-dehydrosilybin on carbon tetrachloride-induced liver injury in rats","volume":"138","author":"Cho","year":"2013","journal-title":"Food Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.arcmed.2018.09.011","article-title":"Antioxidant Activity and Protective Effect of Carob Honey in CCl4-induced Kidney and Liver Injury","volume":"49","author":"Kamoun","year":"2018","journal-title":"Arch. Med Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1136\/gut.47.5.710","article-title":"Evidence of a systemic phenomenon for oxidative stress in cholestatic liver disease","volume":"47","author":"Ljubuncic","year":"2000","journal-title":"Gut"},{"key":"ref_56","first-page":"209","article-title":"Roles of H. rosa sinensis extract in the treatment of liver against CCl4-induced hepatic oxidative stress and antioxidants disorder in male albino rats","volume":"5","author":"Mubarak","year":"2016","journal-title":"Int. J. Med. Plants Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/0891-5849(95)02227-9","article-title":"Structure-antioxidant activity relationships of flavonoids and phenolic acids","volume":"20","author":"Miller","year":"1996","journal-title":"Free Radic. Biol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.jep.2012.06.003","article-title":"Hepatoprotective effect of the ethanol extract of Vitisthun bergii on carbon tetrachloride-induced acute hepatotoxicity in rats through anti-oxidative activities","volume":"142","author":"Deng","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/jgh.12366","article-title":"Regulation by resveratrol of the cellular factors mediating liver damage and regeneration after acute toxic liver injury","volume":"29","author":"Chan","year":"2014","journal-title":"J.Gastroenterol. Hepatol."},{"key":"ref_60","first-page":"3835","article-title":"Role of macrophages in experimental liver injury and repair in mice","volume":"17","author":"Dong","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1002\/cphy.c120026","article-title":"Kupffer Cells in the Liver","volume":"3","author":"Dixon","year":"2013","journal-title":"Compr. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4297206","DOI":"10.1155\/2017\/4297206","article-title":"Cytokines Genotype-Phenotype Correlation in Nonalcoholic Steatohepatitis","volume":"2017","author":"Bocsan","year":"2017","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1111\/j.1478-3231.2011.02495.x","article-title":"Induction of lipocalin-2 expression in acute and chronic experimental liver injury moderated by pro-inflammatory cytokines interleukin-1\u03b2 through nuclear factor-\u03baB activation","volume":"31","author":"Drews","year":"2011","journal-title":"Liver Int."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.3389\/fimmu.2018.02717","article-title":"Lipocalin-2 Functions as Inhibitor of Innate Resistance to Mycobacterium tuberculosis","volume":"9","author":"Dahl","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1177\/0748233714555390","article-title":"Carbon tetrachloride-induced kidney damage and protective effect of Amaranthus lividus L. in rats","volume":"32","author":"Can","year":"2016","journal-title":"Toxicol. Ind. Health"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/0006-2944(82)90011-4","article-title":"Arginine metabolism in rat liver after hepatic damage","volume":"27","author":"Vijaya","year":"1982","journal-title":"Biochem. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1152\/ajpgi.00431.2011","article-title":"Hepatocyte-specific ablation of spermine\/spermidine-N1-acetyltransferase gene reduces the severity of CCl4-induced acute liver injury","volume":"303","author":"Zahedi","year":"2012","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6533","DOI":"10.4049\/jimmunol.167.11.6533","article-title":"Differential Regulation of Nitric Oxide Synthase-2 and Arginase-1 by Type 1\/Type 2 Cytokines in Vivo: Granulomatous Pathology Is Shaped by the Pattern of L-Arginine Metabolism","volume":"167","author":"Hesse","year":"2001","journal-title":"J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0300-483X(00)00437-6","article-title":"Role of macrophages and inflammatory mediators in chemically induced toxicity","volume":"160","author":"Laskin","year":"2001","journal-title":"Toxicology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1104\/pp.010792","article-title":"Genetic Manipulation of the Metabolism of Polyamines in Poplar Cells. The Regulation of Putrescine Catabolism","volume":"128","author":"Bhatnagar","year":"2002","journal-title":"Plant Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s00726-006-0309-y","article-title":"The role of L-arginine in toxic liver failure: Interrelation of arginase, polyamine catabolic enzymes and nitric oxide synthase","volume":"32","author":"Nikolic","year":"2007","journal-title":"Amino Acids"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.foodchem.2013.11.058","article-title":"Hepatoprotective effects of fermented Curcuma longa L. on carbon tetrachloride-induced oxidative stress in rats","volume":"151","author":"Kim","year":"2014","journal-title":"Food Chem."},{"key":"ref_73","first-page":"268","article-title":"Effect of Silybum marianum on acute hepatic damage caused by carbon tetrachloride in rats","volume":"23","author":"Ozturk","year":"2012","journal-title":"Biomed. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"7832","DOI":"10.1021\/acs.jafc.9b02567","article-title":"Reduction of Aging-Induced Oxidative Stress and Activation of Autophagy by Bilberry Anthocyanin Supplementation via the AMPK\u2212mTOR Signaling Pathway in Aged Female Rats","volume":"67","author":"Li","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1021\/jf960421t","article-title":"Oxygen Radical Absorbing Capacity of Anthocyanins","volume":"45","author":"Wang","year":"1997","journal-title":"J. Agric.Food Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1021\/jf025551i","article-title":"Antioxidant activity of anthocyanins and their Aglycons","volume":"51","author":"Heinonen","year":"2003","journal-title":"J. Agric.Food Chem."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/8\/10\/451\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:27:33Z","timestamp":1760189253000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/8\/10\/451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,4]]},"references-count":77,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,10]]}},"alternative-id":["antiox8100451"],"URL":"https:\/\/doi.org\/10.3390\/antiox8100451","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,4]]}}}