Protective effect of resveratrol against methotrexate-induced oxidative stress in the small intestinal tissues of rats

Abstract

The effect of resveratrol on the damage induced by methotrexate (MTX) in rat duodenum and jejunum tissue was investigated and evaluated in comparison with famotidine. The rats were divided into four groups as healthy group (HG), resveratrol+MTX (RMTX) group, famotidine+MTX (FMTX) group and the control group which received MTX (MTXC). RMTX group was given resveratrol 25 mg/kg and FMTX group famotidin 25 mg/kg, while MTXC and HG groups were orally administered distilled water once a day for 30 days. The rats in RMTX, FMTX and MTXC groups were given MTX of 5 mg/kg dose by the same way for 30 days. At the end of this period, amount of MDA, 8-OH/Gua and tGSH, and MPO gene expression were measured in the duodenal and jejunal tissues and the results were histopathologically evaluated. Resveratrol and famotidine were found to significantly prevent elevation of the MDA, 8-OH/Gua and MPO parameters with MTX and decrease of the levels of tGSH in the duodenal and jejunal tissues. Both drugs prevented severe damage to the villus and crypt epithelium in the duodenum and jejunum, congestion and hemorrhage, inflammatory cell infiltration and necrosis in the mucosa and submucosa due to MTX administration. Resveratrol could be considered in the clinical practice for treatment of the tissue damage in the intestines due to use of MTX, in comparison with famotidine. Resveratrol may be more advantageous than famotidine in long-term use against MTX toxicity since it does not inhibit gastric acid secretion.

Keywords: Resveratrol; oxidative stress; small intestine.

Figure 1

The effects of Resveratrol and Famotidin on MDA, tGSH and 8-OH/Gua levels in the duodenal tissues of rats given methotrexate. Bars are mean ± SEM. RMTX, FMTX and HG groups are compared with MTXC group. **: P<0.001.

Figure 2

The effects of Resveratrol and Famotidin on MDA, tGSH and 8-OH/Gua levels in the jejunal tissue of rats given methotrexate. Bars are mean ± SEM. RMTX, FMTX and HG groups are compared with MTXC group. **: P<0.001.

Figure 3

The effects of Resveratrol and Famotidin on MPO gene expression in the duodenal and jejunal tissues of rats given MTX. RMTX, FMTX and HG groups are compared with MTXC group. **: P<0.001.

Figure 4

A. The histo-pathological examination of the duodenum tissue of healthy group (HG), (H&E ×100), B. The histo-pathological examination of the jejunum tissue of healthy group (HG), (H&E ×100).

Figure 5

A. Section of the duodenum tissue of MTXC group (H&E ×400), B. Section of the duodenum tissue of MTXC group (H&E ×200), C. Section of the duodenum tissue of MTXC group (H&E ×400), D. Section of the duodenum tissue of MTXC group (H&E ×100), E. Section of the duodenum tissue of RMTX group (H&E ×100), F. Section of the duodenum tissue of FMTX group (H&E ×100).

Figure 6

A. Section of the jejunum tissue of MTXC group (H&E ×400), B. Section of the jejunum tissue of MTXC group (H&E ×400), C. Section of the jejunum tissue of RMTX group (H&E ×100), D. Section of the jejunum tissue of FMTX group (H&E ×100).