Cytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats

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dc.contributor.authorAkbulut, Sami
dc.contributor.authorElbe, Hulya
dc.contributor.authorEris, Cengiz
dc.contributor.authorDogan, Zumrut
dc.contributor.authorToprak, Gulten
dc.contributor.authorOtan, Emrah
dc.contributor.authorErdemli, Erman
dc.date.accessioned2024-04-24T17:20:57Z
dc.date.available2024-04-24T17:20:57Z
dc.date.issued2014
dc.departmentDicle Üniversitesien_US
dc.description.abstractAIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity. METHODS: An MTX-induced hepatotoxicity model was established in 44 male Sprague Dawley rats by administration of a single intraperitoneal injection of 20 mg/kg MTX. Eleven of the rats were left untreated (Model group; n = 11), and the remaining rats were treated with a 7-d course of 50 mg/kg per day NAC (MTX + NAC group; n = 11), 50 mg/kg per single dose AMF (MTX + AMF group; n = 11), or 10 mg/kg per day ASC (MTX + ASC group; n = 11). Eleven rats that received no MTX and no treatments served as the negative control group. Structural and functional changes related to MTX- and the various treatments were assessed by histopathological analysis of liver tissues and biochemical assays of malondialdehyde (MDA), superoxide dismutase (SOD), catalase, glutathione (GSH) and xanthine oxidase activities and of serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total bilirubin. RESULTS: Exposure to MTX caused structural and functional hepatotoxicity, as evidenced by significantly worse histopathological scores [median (range) injury score: control group: 1 (0-3) vs 7 (6-9), p = 0.001] and significantly higher MDA activity [409 (352-466) nmol/g vs 455.5 (419-516) nmol/g, p < 0.05]. The extent of MTX-induced perturbation of both parameters was reduced by all three cytoprotective agents, but only the reduction in hepatotoxicity scores reached statistical significance [4 (3-6) for NAC, 4.5 (3-5) for AMF and 6 (5-6) for ASC; p = 0.001, p = 0.001 and p < 0.005 vs model group respectively]. Exposure to MTX also caused a significant reduction in the activities of GSH and SOD antioxidants in liver tissues [control group: 3.02 (2.85-3.43) mu mol/g and 71.78 (61.88-97.81) U/g vs model group: 2.52 (2.07-3.34) mu mol/g and 61.46 (58.27-67.75) U/g, p < 0.05]; however, only the NAC treatment provided significant increases in these antioxidant enzyme activities [3.22 (2.54-3.62) mu mol/g and 69.22 (61.13-100.88) U/g, p < 0.05 and p < 0.01 vs model group respectively]. CONCLUSION: MTX-induced structural and functional damage to hepatic tissues in rats may involve oxidative stress, and cytoprotective agents (NAC > AMF > ASC) may alleviate MTX hepatotoxicity. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.en_US
dc.identifier.doi10.3748/wjg.v20.i29.10158
dc.identifier.endpage10165en_US
dc.identifier.issn1007-9327
dc.identifier.issn2219-2840
dc.identifier.issue29en_US
dc.identifier.pmid25110444
dc.identifier.scopus2-s2.0-84905845192
dc.identifier.scopusqualityQ1
dc.identifier.startpage10158en_US
dc.identifier.urihttps://doi.org/10.3748/wjg.v20.i29.10158
dc.identifier.urihttps://hdl.handle.net/11468/19316
dc.identifier.volume20en_US
dc.identifier.wosWOS:000340730300041
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoenen_US
dc.publisherBaishideng Publishing Group Incen_US
dc.relation.ispartofWorld Journal of Gastroenterology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectMethotrexateen_US
dc.subjectAmifostineen_US
dc.subjectN-Acetyl Cysteineen_US
dc.subjectAscorbic Aciden_US
dc.subjectHepatotoxicityen_US
dc.subjectOxidative Stressen_US
dc.titleCytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in ratsen_US
dc.titleCytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats
dc.typeArticleen_US

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