{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T19:31:30Z","timestamp":1773171090870,"version":"3.50.1"},"reference-count":66,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T00:00:00Z","timestamp":1573516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PD\/BD\/109634\/2015"],"award-info":[{"award-number":["PD\/BD\/109634\/2015"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/107708\/2015"],"award-info":[{"award-number":["SFRH\/BD\/107708\/2015"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union FEDER","award":["POCI\/01\/0145\/FEDER\/007728; POCI-01-0145-FEDER-029584; POCI\/01\/0145\/FEDER\/007265"],"award-info":[{"award-number":["POCI\/01\/0145\/FEDER\/007728; POCI-01-0145-FEDER-029584; POCI\/01\/0145\/FEDER\/007265"]}]},{"name":"FCT\/MEC","award":["UID\/MULTI\/04378\/2013; UID\/QUI\/50006\/2013"],"award-info":[{"award-number":["UID\/MULTI\/04378\/2013; UID\/QUI\/50006\/2013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Gold nanoparticles (AuNPs) are promising nanoplatforms for drug therapy, diagnostic and imaging. However, biological comparison studies for different types of AuNPs fail in consistency due to the lack of sensitive methods to detect subtle differences in the expression of toxicity. Therefore, innovative and sensitive approaches such as metabolomics are much needed to discriminate toxicity, specially at low doses. The current work aims to compare the in vivo toxicological effects of gold nanospheres versus gold nanostars (of similar ~40 nm diameter and coated with 11-mercaptoundecanoic acid) 24 h after an intravenous administration of a single dose (1.33 \u00d7 1011 AuNPs\/kg) to Wistar rats. The biodistribution of both types of AuNPs was determined by graphite furnace atomic absorption spectroscopy. The metabolic effects of the AuNPs on their main target organ, the liver, were analyzed using a GC-MS-based metabolomic approach. Conventional toxicological endpoints, including the levels of ATP and reduced and oxidized glutathione, were also investigated. The results show that AuNPs preferentially accumulate in the liver and, to a lesser extent, in the spleen and lungs. In other organs (kidney, heart, brain), Au content was below the limit of quantification. Reduced glutathione levels increased for both nanospheres and nanostars in the liver, but ATP levels were unaltered. Multivariate analysis showed a good discrimination between the two types of AuNPs (sphere- versus star-shaped nanoparticles) and compared to control group. The metabolic pathways involved in the discrimination were associated with the metabolism of fatty acids, pyrimidine and purine, arachidonic acid, biotin, glycine and synthesis of amino acids. In conclusion, the biodistribution, toxicological, and metabolic profiles of gold nanospheres and gold nanostars were described. Metabolomics proved to be a very useful tool for the comparative study of different types of AuNPs and raised awareness about the pathways associated to their distinct biological effects.<\/jats:p>","DOI":"10.3390\/nano9111606","type":"journal-article","created":{"date-parts":[[2019,11,13]],"date-time":"2019-11-13T09:11:27Z","timestamp":1573636287000},"page":"1606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A Metabolomic Approach for the In Vivo Study of Gold Nanospheres and Nanostars after a Single-Dose Intravenous Administration to Wistar Rats"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5429-5874","authenticated-orcid":false,"given":"Maria","family":"Enea","sequence":"first","affiliation":[{"name":"UCIBIO\/REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"LAQV\/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4073-2121","authenticated-orcid":false,"given":"Ana Margarida","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"UCIBIO\/REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8621-4701","authenticated-orcid":false,"given":"Miguel","family":"Peixoto de Almeida","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"given":"Maria Elisa","family":"Soares","sequence":"additional","affiliation":[{"name":"UCIBIO\/REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2583-5624","authenticated-orcid":false,"given":"Salom\u00e9","family":"Gon\u00e7alves-Monteiro","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Department of Drug Sciences, Laboratory of Pharmacology, Faculty of Pharmacy, University of Porto, 4150-755 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7395-5700","authenticated-orcid":false,"given":"Paula","family":"Guedes de Pinho","sequence":"additional","affiliation":[{"name":"UCIBIO\/REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2086-5696","authenticated-orcid":false,"given":"Eul\u00e1lia","family":"Pereira","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9895-503X","authenticated-orcid":false,"given":"Maria de Lourdes","family":"Bastos","sequence":"additional","affiliation":[{"name":"UCIBIO\/REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6650-5285","authenticated-orcid":false,"given":"Helena","family":"Carmo","sequence":"additional","affiliation":[{"name":"UCIBIO\/REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1002\/adhm.201501035","article-title":"Cancer cell internalization of gold nanostars impacts their photothermal efficiency in vitro and in vivo: Toward a plasmonic thermal fingerprint in tumoral environment","volume":"5","author":"Espinosa","year":"2016","journal-title":"Adv. Healthc. Mater."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhu, H., Liu, W., Cheng, Z., Yao, K., Yang, Y., Xu, B., and Su, G. (2017). Targeted delivery of siRNA with pH-responsive hybrid gold nanostars for cancer treatment. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102029"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mioc, A., Mioc, M., Ghiulai, R., Voicu, M., Babuta, R., Trandafirescu, C., Dehelean, C., Coricovac, D., and Soica, C.M. (2019). Gold nanoparticles as targeted delivery systems and theranostic agents in cancer therapy. Curr. Med. Chem.","DOI":"10.2174\/0929867326666190506123721"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1158\/0008-5472.CAN-12-2071","article-title":"Superior penetration and retention behavior of 50 nm gold nanoparticles in tumors","volume":"73","author":"Huo","year":"2013","journal-title":"Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.aca.2017.07.045","article-title":"Surface enhanced infrared absorption spectroscopy based on gold nanostars and spherical nanoparticles","volume":"990","author":"Bibikova","year":"2017","journal-title":"Anal. Chim. Acta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3389\/fchem.2015.00051","article-title":"Multifunctional gold nanostars for molecular imaging and cancer therapy","volume":"3","author":"Liu","year":"2015","journal-title":"Front. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3449","DOI":"10.1002\/jbm.a.35491","article-title":"Shape and surface effects on the cytotoxicity of nanoparticles: Gold nanospheres versus gold nanostars","volume":"103","author":"Favi","year":"2015","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s10856-017-5902-y","article-title":"Size and shape-dependent cytotoxicity profile of gold nanoparticles for biomedical applications","volume":"28","author":"Wozniak","year":"2017","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"055101","DOI":"10.1088\/0957-4484\/26\/5\/055101","article-title":"Comparative toxicity evaluation of flower-shaped and spherical gold nanoparticles on human endothelial cells","volume":"26","author":"Sultana","year":"2015","journal-title":"Nanotechnology"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Enea, M., Peixoto de Almeida, M., Eaton, P., Dias da Silva, D., Pereira, E., Soares, M.E., Bastos, M.L., and Carmo, H. (2019). A multiparametric study of gold nanoparticles cytotoxicity, internalization and permeability using an in vitro model of blood-brain barrier. Influence of size, shape and capping agent. Nanotoxicology, 13.","DOI":"10.1080\/17435390.2019.1621398"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1016\/j.nano.2014.06.005","article-title":"Short-and long-term distribution and toxicity of gold nanoparticles in the rat after a single-dose intravenous administration","volume":"10","author":"Fraga","year":"2014","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ejpb.2011.09.005","article-title":"Effect of surface coating on the biodistribution profile of gold nanoparticles in the rat","volume":"80","author":"Morais","year":"2012","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"736","DOI":"10.3109\/17435390.2015.1121412","article-title":"A combined proteomics and metabolomics approach to assess the effects of gold nanoparticles in vitro","volume":"10","author":"Gioria","year":"2016","journal-title":"Nanotoxicology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1080\/17435390.2018.1432779","article-title":"Metabolomics reveals the depletion of intracellular metabolites in HepG2 cells after treatment with gold nanoparticles","volume":"12","author":"Lindeque","year":"2018","journal-title":"Nanotoxicology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"14","DOI":"10.5483\/BMBRep.2018.51.1.237","article-title":"Integration of metabolomics and transcriptomics in nanotoxicity studies","volume":"51","author":"Shin","year":"2018","journal-title":"BMB Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1007\/s11095-006-0025-z","article-title":"Metabonomics techniques and applications to pharmaceutical research & development","volume":"23","author":"Lindon","year":"2006","journal-title":"Pharm. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1007\/s00204-018-2314-9","article-title":"GC-MS metabolomics reveals disturbed metabolic pathways in primary mouse hepatocytes exposed to subtoxic levels of 3,4-methylenedioxymethamphetamine (MDMA)","volume":"92","author":"Araujo","year":"2018","journal-title":"Arch. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Palomino-Schatzlein, M., Garcia, H., Gutierrez-Carcedo, P., Pineda-Lucena, A., and Herance, J.R. (2017). Assessment of gold nanoparticles on human peripheral blood cells by metabolic profiling with 1H-NMR spectroscopy, a novel translational approach on a patient-specific basis. PloS. ONE, 12.","DOI":"10.1371\/journal.pone.0189748"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nano.2017.08.011","article-title":"Gold nanoparticles: Distribution, bioaccumulation and toxicity. In vitro and in vivo studies","volume":"14","author":"Bettmer","year":"2018","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11098","DOI":"10.1021\/la201938u","article-title":"Kinetically controlled seeded growth synthesis of citrate-stabilized gold nanoparticles of up to 200 nm: Size focusing versus Ostwald ripening","volume":"27","author":"Bastus","year":"2011","journal-title":"Langmuir"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s13404-012-0069-2","article-title":"Effect of high gold salt concentrations on the size and polydispersity of gold nanoparticles prepared by an extended Turkevich\u2013Frens method","volume":"45","author":"Zabetakis","year":"2012","journal-title":"Gold Bull."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"075102","DOI":"10.1088\/0957-4484\/23\/7\/075102","article-title":"Gold nanostars: Surfactant-free synthesis, 3D modelling, and two-photon photoluminescence imaging","volume":"23","author":"Yuan","year":"2012","journal-title":"Nanotechnology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1038\/nprot.2011.375","article-title":"Global urinary metabolic profiling procedures using gas chromatography\u2013mass spectrometry","volume":"6","author":"Chan","year":"2011","journal-title":"Nat. Protoc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1039\/c3mb70194h","article-title":"Trials and tribulations of \u2018omics data analysis: Assessing quality of SIMCA-based multivariate models using examples from pulmonary medicine","volume":"9","author":"Wheelock","year":"2013","journal-title":"Mol. BioSyst."},{"key":"ref_25","first-page":"92","article-title":"Multivariate analysis in metabolomics","volume":"1","author":"Worley","year":"2013","journal-title":"Curr. Metabol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"W486","DOI":"10.1093\/nar\/gky310","article-title":"MetaboAnalyst 4.0: Towards more transparent and integrative metabolomics analysis","volume":"46","author":"Chong","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1007\/s00204-018-2227-7","article-title":"Ethanol addictively enhances the in vitro cardiotoxicity of cocaine through oxidative damage, energetic deregulation, and apoptosis","volume":"92","author":"Martins","year":"2018","journal-title":"Arch. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17408","DOI":"10.1021\/acs.jpcc.5b03624","article-title":"Extinction coefficient of gold nanostars","volume":"119","author":"Tam","year":"2015","journal-title":"J. Phys. Chem. C"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"20568","DOI":"10.1021\/acsami.5b04290","article-title":"Protein corona influences cellular uptake of gold nanoparticles by phagocytic and nonphagocytic cells in a size-dependent manner","volume":"7","author":"Cheng","year":"2015","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1021\/acs.bioconjchem.6b00605","article-title":"Multiparametric assessment of gold nanoparticle cytotoxicity in cancerous and healthy cells: The role of size, shape, and surface chemistry","volume":"28","author":"Bhamidipati","year":"2017","journal-title":"Bioconjugate Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7992","DOI":"10.1039\/C5NR08808A","article-title":"Gold nanoparticle size and shape influence on osteogenesis of mesenchymal stem cells","volume":"8","author":"Li","year":"2016","journal-title":"Nanoscale"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3475","DOI":"10.2147\/IJN.S106073","article-title":"Effects of surface charges of gold nanoclusters on long-term in vivo biodistribution, toxicity, and cancer radiation therapy","volume":"11","author":"Wang","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.colsurfb.2008.07.004","article-title":"Biodistribution of colloidal gold nanoparticles after intravenous administration: Effect of particle size","volume":"66","author":"Sonavane","year":"2008","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e1801451","DOI":"10.1002\/smll.201801451","article-title":"Size, shape and protein corona determine cellular uptake and removal mechanisms of gold nanoparticles","volume":"14","author":"Ding","year":"2018","journal-title":"Small"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8044","DOI":"10.1021\/acs.jafc.5b03242","article-title":"Uptake of gold nanoparticles by intestinal epithelial cells: Impact of particle size on their absorption, accumulation, and toxicity","volume":"63","author":"Yao","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s11671-019-2967-1","article-title":"Shape-dependent cytotoxicity and cellular uptake of gold nanoparticles synthesized using green tea extract","volume":"14","author":"Lee","year":"2019","journal-title":"Nanoscale Res. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1166\/jnn.2011.3094","article-title":"Shape dependence of gold nanoparticles on in vivo acute toxicological effects and biodistribution","volume":"11","author":"Sun","year":"2011","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1039\/C8AN01827H","article-title":"A translational approach to assess the metabolomic impact of stabilized gold nanoparticles by NMR spectroscopy","volume":"144","author":"Herance","year":"2019","journal-title":"Analyst"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.aca.2015.10.001","article-title":"From sample treatment to biomarker discovery: A tutorial for untargeted metabolomics based on GC-(EI)-Q-MS","volume":"900","author":"Mastrangelo","year":"2015","journal-title":"Anal. Chim. Acta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1002\/cem.1187","article-title":"CV-ANOVA for significance testing of PLS and OPLS (R) models","volume":"22","author":"Eriksson","year":"2008","journal-title":"J. Chemom."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1021\/pr060594q","article-title":"Chemometrics in metabonomics","volume":"6","author":"Trygg","year":"2007","journal-title":"J. Proteom. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s11306-007-0099-6","article-title":"Assessment of PLSDA cross validation","volume":"4","author":"Westerhuis","year":"2008","journal-title":"Metabolomics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4844","DOI":"10.1007\/s11356-015-5683-0","article-title":"Surface capping and size-dependent toxicity of gold nanoparticles on different trophic levels","volume":"23","author":"Iswarya","year":"2016","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.cbi.2009.11.028","article-title":"Pyrogallol-mediated toxicity and natural antioxidants: Triumphs and pitfalls of preclinical findings and their translational limitations","volume":"183","author":"Upadhyay","year":"2010","journal-title":"Chem. Biol. Interact."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4318","DOI":"10.1002\/1873-3468.12461","article-title":"Choline and dimethylglycine produce superoxide\/hydrogen peroxide from the electron transport chain in liver mitochondria","volume":"590","author":"Mailloux","year":"2016","journal-title":"FEBS Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5996","DOI":"10.1016\/j.biomaterials.2010.04.014","article-title":"Autophagy and oxidative stress associated with gold nanoparticles","volume":"31","author":"Li","year":"2010","journal-title":"Biomaterials"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/WOX.0b013e3182439613","article-title":"Oxidative stress and antioxidant defense","volume":"5","author":"Birben","year":"2012","journal-title":"World Allergy Organ. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1152\/ajpgi.00001.2006","article-title":"Mechanisms of liver injury. III. Role of glutathione redox status in liver injury","volume":"291","author":"Han","year":"2006","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.mam.2008.05.005","article-title":"Regulation of glutathione synthesis","volume":"30","author":"Lu","year":"2009","journal-title":"Mol. Asp. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1158\/0008-5472.CAN-06-1794","article-title":"Inhibition of fatty acid synthase induces endoplasmic reticulum stress in tumor cells","volume":"67","author":"Little","year":"2007","journal-title":"Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.bbalip.2013.10.013","article-title":"Identification of genes and pathways involved in the synthesis of Mead acid (20:3n-9), an indicator of essential fatty acid deficiency","volume":"1841","author":"Ichi","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.plipres.2015.04.002","article-title":"Is docosahexaenoic acid synthesis from \u03b1-linolenic acid sufficient to supply the adult brain?","volume":"59","author":"Domenichiello","year":"2015","journal-title":"Prog. Lipid Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1146\/annurev.pathmechdis.3.121806.151409","article-title":"Anti-inflammatory and proresolving lipid mediators","volume":"3","author":"Serhan","year":"2008","journal-title":"Annu. Rev. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1042\/BST0391240","article-title":"Lipidomics of polyunsaturated-fatty-acid-derived oxygenated metabolites","volume":"39","author":"Massey","year":"2011","journal-title":"Biochem. Soc. Trans."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"360438","DOI":"10.1155\/2014\/360438","article-title":"Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal","volume":"2014","author":"Ayala","year":"2014","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1172\/JCI200422422","article-title":"Molecular mediators of hepatic steatosis and liver injury","volume":"114","author":"Browning","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.plipres.2017.01.002","article-title":"Sphingolipids and glycerophospholipids-The \u2019ying and yang\u2019 of lipotoxicity in metabolic diseases","volume":"66","author":"Pellegrinelli","year":"2017","journal-title":"Prog. Lipid Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1505s","DOI":"10.1093\/ajcn\/83.6.1505S","article-title":"N-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases","volume":"83","author":"Calder","year":"2006","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s002100000308","article-title":"Signaling by extracellular nucleotides and nucleosides","volume":"362","author":"Illes","year":"2000","journal-title":"Naunyn Schmiedeberg Arch. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e0018","DOI":"10.1199\/tab.0018","article-title":"Purine and pyrimidine nucleotide synthesis and metabolism","volume":"1","author":"Moffatt","year":"2002","journal-title":"Arabidopsis B."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ymgme.2005.07.027","article-title":"Disorders of purine and pyrimidine metabolism","volume":"86","author":"Nyhan","year":"2005","journal-title":"Mol. Genet. Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s42003-018-0271-8","article-title":"Regulation of RNA editing by RNA-binding proteins in human cells","volume":"2","author":"Tran","year":"2019","journal-title":"Commun. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jprot.2017.03.007","article-title":"Functional proteomic analysis of corticosteroid pharmacodynamics in rat liver: Relationship to hepatic stress, signaling, energy regulation, and drug metabolism","volume":"160","author":"Ayyar","year":"2017","journal-title":"J. Proteom."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7117","DOI":"10.1016\/j.biomaterials.2013.05.043","article-title":"Selective metabolic effects of gold nanorods on normal and cancer cells and their application in anticancer drug screening","volume":"34","author":"Zhang","year":"2013","journal-title":"Biomaterials"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"8265","DOI":"10.1039\/C4NR01035C","article-title":"Metabolomic profiles delineate the potential role of glycine in gold nanorod-induced disruption of mitochondria and blood-testis barrier factors in TM-4 cells","volume":"6","author":"Xu","year":"2014","journal-title":"Nanoscale"}],"container-title":["Nanomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4991\/9\/11\/1606\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:33:53Z","timestamp":1760189633000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4991\/9\/11\/1606"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,12]]},"references-count":66,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["nano9111606"],"URL":"https:\/\/doi.org\/10.3390\/nano9111606","relation":{},"ISSN":["2079-4991"],"issn-type":[{"value":"2079-4991","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,12]]}}}