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

Abstract

Objective: 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-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and myeloperoxidase (MPO) were also performed. Hematoxylin and eosin-stained paraffinembedded 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. Results: The administration of MTX in group 1 yielded a higher level of MDA (8.33 +/- 2.5 mu mol/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-1 beta (40.33 +/- 5.43 gene expression levels), TNF-alpha (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-1 beta, TNF-alpha 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. Conclusion: In this study, ileal damage caused by MTX was inhibited by RST. (C) 2015 S. Karger AG, Basel