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

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dc.contributor.author Akbulut, Sami
dc.contributor.author Elbe, Hulya
dc.contributor.author Eris, Cengiz
dc.contributor.author Dogan, Zümrüt
dc.contributor.author Toprak, Gülten
dc.contributor.author Otan, Emrah
dc.contributor.author Erdemli, Erman
dc.contributor.author Turkoz, Yusuf
dc.date.accessioned 2020-07-14T09:49:49Z
dc.date.available 2020-07-14T09:49:49Z
dc.date.issued 2014-08
dc.identifier.citation Akbulut, S., Elbe, H., Eris, C., Dogan, Z., Toprak, G., Otan, E., Erdemli, E., Turkoz, Y. Cytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats. (2014). WORLD JOURNAL OF GASTROENTEROLOGY. tr_TR
dc.identifier.issn 1007-9327
dc.identifier.issn 2219-2840
dc.identifier.other DOI: 10.3748/wjg.v20.i29.10158
dc.identifier.uri http://abakus.inonu.edu.tr/xmlui/handle/123456789/16875
dc.description WORLD JOURNAL OF GASTROENTEROLOGY Volume: 20 Issue: 29 Pages: 10158-10165 DOI: 10.3748/wjg.v20.i29.10158 Published: AUG 21 2014 Document Type:Article tr_TR
dc.description.abstract AIM: 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. tr_TR
dc.language.iso en tr_TR
dc.subject Oxidative stress tr_TR
dc.subject N-acetyl cysteine tr_TR
dc.subject Hepatotoxicity tr_TR
dc.subject Ascorbic acid tr_TR
dc.subject Amifostine tr_TR
dc.subject Methotrexate tr_TR
dc.title Cytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats tr_TR
dc.type Article tr_TR

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