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The Impact of Resveratrol on Oxidative Stress Induced by Methotrexate in Rat Ileum Tissue: Evaluation of Biochemical and Histopathological Features and Analysis of Gene Expression

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      The aim of this study was to assess the impact of resveratrol (RST) on oxidative stress induced by methotrexate in rat ileum tissue.

      Materials and Methods

      Twenty-four rats were divided into 4 groups with 6 in each group. Each rat was orally administered the following every day for 30 days: group 1 (MTXG), methotrexate (MTX; 5 mg/kg); group 2 (RMTXG), MTX (5 mg/kg) plus RST (25 mg/kg/day); group 3 (RSTG), RST alone (25 mg/kg/day), and group 4 (controls), distilled water. After the rats had been sacrified, the ilea were removed for the assessment of malondialdehyde (MDA), total glutathione (tGSH) and glutathione peroxidase (GSH-Px). Gene expression analyses for interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) were also performed. Hematoxylin and eosin-stained paraffin-embedded sections of the ileum were analyzed under a light microscope and the findings were recorded. Statistical analyses of the data were performed using one-way ANOVA.


      The administration of MTX in group 1 yielded a higher level of MDA (8.33 ± 2.5 μmol/g protein, p < 0.001) and lower levels of tGSH (0.97 ± 0.29 nmol/g protein) and GSH-Px (5.22 ± 0.35 U/g protein, p < 0.001) compared to the other groups. MTX also increased IL-1β (40.33 ± 5.43 gene expression levels), TNF-α (6.08 ± 0.59) and MPO gene expression (9 ± 1.41) in group 1 compared to the controls (11.33 ± 2.07, 2.15 ± 0.33 and 3.43 ± 0.48, respectively, p < 0.001). The impact of RST on IL-1β, TNF-α and MPO gene expression induced by MTX was observed as a reversal of these findings (p < 0.05). Severe inflammation, damage to the villus epithelium and crypt necrosis was observed histopathologically in the MTXG group, whereas only mild inflammation was seen in the RMTXG group.


      In this study, ileal damage caused by MTX was inhibited by RST.

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      Most cited references 30

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            Author and article information

            aDepartment of Internal Medicine, Istanbul Medeniyet University, Istanbul, Turkey
            bDepartment of Pharmacology, Faculty of Medicine, Erzincan University, Istanbul, Turkey
            cDepartment of Pathology, Mengucek Gazi Training and Research Hospital, Erzincan, Departments of, Istanbul, Turkey
            dDepartment of Anatomy, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey
            eDepartment of Biochemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Istanbul, Turkey
            fDepartment of Histology and Embryology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Istanbul, Turkey
            gDepartment of Department of Medical Genetics, Goztepe Training and Research Hospital, Istanbul Medeniyet University, Istanbul, Turkey
            Author notes
            *Dr. Adalet Ozcicek, Department of Internal Medicine, Faculty of Medicine, Erzincan University, Haci Ali Akin Street, TR—24030 Erzincan (Turkey), E-Mail draozcicek@
            Med Princ Pract
            Med Princ Pract
            Medical Principles and Practice
            S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, )
            February 2016
            30 October 2015
            30 October 2015
            : 25
            : 2
            : 181-186
            26517535 5588348 10.1159/000442020 mpp-0025-0181
            Copyright © 2015 by S. Karger AG, Basel

            This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (, applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.

            Figures: 1, Tables: 2, References: 30, Pages: 6
            Original Paper


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