{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T23:12:23Z","timestamp":1762125143079,"version":"build-2065373602"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,3,6]],"date-time":"2009-03-06T00:00:00Z","timestamp":1236297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The metabonomic approach has been widely used in toxicology to investigate mechanisms of toxicity. In the present study alterations in the metabolic profiles, monitored by <jats:sup>1<\/jats:sup>H\u2010NMR spectroscopy, on serum samples in acetaminophen (APAP)\u2010induced liver injury in rabbits were examined. Furthermore, the effect of the established antidote <jats:italic>N<\/jats:italic>\u2010acetylcysteine (NAC) and the proposed antidotes silybinin (SIL), cimetidine (CIM) and SIL\/CIM was also investigated. A single dose of APAP (2\u00a0g\u00a0kg<jats:sup>\u22121<\/jats:sup> b.w., i.g.) was administered to rabbits and APAP combined with the antidotes SIL, CIM and NAC. Animals were sacrificed at 24\u00a0h post\u2010APAP treatment. Healthy untreated animals served as controls. <jats:sup>1<\/jats:sup>H\u2010NMR spectra of serum samples were acquired and underwent principal component analysis (PCA). Acute liver injury was verified by histopathological examination and the alterations of serum biochemical enzymes AST and ALT. <jats:sup>1<\/jats:sup>H\u2010NMR spectroscopy revealed variations in the serum metabolic profile of APAP\u2010intoxicated rabbits compared with controls. Co\u2010administration of APAP with NAC, CIM and SIL + CIM seems to ameliorate the metabolic profile of animals compared with simply APAP\u2010treated ones. In this study, the model of APAPinduced liver injury was successfully described using the <jats:sup>1<\/jats:sup>H\u2010NMR based metabonomic approach in serum. Furthermore, the use of antidotes that reduced the toxic insult was also recorded using this technique. The combination of NMR spectroscopy and PCA is a rapid methodology, capable of detecting alterations in the metabolic profile, and produces adequate models that could be used for the characterization of unknown samples, both experimental and clinical, reinforcing its future use in clinical settings.Copyright \u00a9 2009 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.1425","type":"journal-article","created":{"date-parts":[[2009,3,6]],"date-time":"2009-03-06T06:29:04Z","timestamp":1236320944000},"page":"395-402","source":"Crossref","is-referenced-by-count":12,"title":["Acute liver acetaminophen toxicity in rabbits and the use of antidotes: a metabonomic approach in serum"],"prefix":"10.1002","volume":"29","author":[{"given":"Athina","family":"Zira","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel","family":"Mikros","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantina","family":"Giannioti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panagiota","family":"Galanopoulou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Apostolos","family":"Papalois","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charis","family":"Liapi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stamatios","family":"Theocharis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,3,6]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfh151"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jen.2004.01.023"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0901-9928.2000.860602.x"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2004.06.031"},{"key":"e_1_2_1_6_1","first-page":"611","article-title":"Silymarin mediated differential modulation of toxicity induced by carbon tetrachloride, paracetamol and d\u2010galactosamine in freshly isolated rat hepatocytes","volume":"35","author":"Chrungoo VJ","year":"1997","journal-title":"Indian J. Exp. Biol"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx0256127"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2003.12.019"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2006.10.007"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(03)00053-1"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875-9114.1997.tb03721.x"},{"key":"e_1_2_1_12_1","first-page":"1","article-title":"Council Directive 86\/609\/ECC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes","volume":"358","author":"European Community.","year":"1986","journal-title":"Official J. Eur. Union"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03190363"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.1248"},{"key":"e_1_2_1_15_1","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1093\/clinchem\/24.4.720","volume":"24","author":"International Federation of Clinical Chemistry. Committee on Standards, Enzyme Panel","year":"1978","journal-title":"Clin. Chem"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/62.2.212"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20293"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.MPG.0000158524.30294.E2"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/13547500410001668379"},{"volume-title":"The Clinical Chemistry of Laboratory Animals","year":"1989","author":"Loeb WF","key":"e_1_2_1_20_1"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.2550140205"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510300104"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/004982599238047"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(97)82332-X"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.3.5722.557"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfi102"},{"key":"e_1_2_1_27_1","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/S0022-3565(25)23715-6","article-title":"Additive protection of cimetidine and N\u2010acetylcysteine treatment against acetaminophen\u2010induced hepatic necrosis in the rat","volume":"234","author":"Speeg KV","year":"1985","journal-title":"J. Pharmacol. Exp. Ther"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/00045391-200501000-00009"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-962056"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2003.07.026"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx049869b"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr0601584"},{"volume-title":"Hepatotoxicity. The Adverse Effects of Drugs and Other Chemicals on the Liver","year":"1999","author":"Zimmerman HJ.","key":"e_1_2_1_33_1"},{"issue":"4","key":"e_1_2_1_34_1","first-page":"621A","article-title":"Integrated metabonomic investigation in the model of liver injury and regeneration induced by CCl4 in rats","volume":"46","author":"Zira A","year":"2007","journal-title":"Hepatology"},{"key":"e_1_2_1_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.1000"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21075"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjat.1425","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.1425","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T08:41:26Z","timestamp":1760517686000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.1425"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3,6]]},"references-count":35,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2009,7]]}},"alternative-id":["10.1002\/jat.1425"],"URL":"https:\/\/doi.org\/10.1002\/jat.1425","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"type":"print","value":"0260-437X"},{"type":"electronic","value":"1099-1263"}],"subject":[],"published":{"date-parts":[[2009,3,6]]}}}