Gallic Acid Protects Against Methotrexate-Induced Intestinal Mucositis; Oxidative Stress, Histopathology and Inflammatory Status

Abstract

Background: Gastrointestinal (GI) mucositis is one of the serious side effects of methotrexate (MTX) treatment. It is known that oxidative stress plays an important role in drug-induced side effects. Objectives: The present study aimed to assess the effect of gallic acid (GA) against MTX-induced intestinal mucositis in male Wistar rats. Methods: Twenty-eight adult male Wistar rats were randomly divided into 4 groups (n = 7), including (1) control group; (2) GA group (gallic acid: 30 mg/kg/day, orally); (3) MTX group [20 mg/kg, intra peritoneal (IP)]; and (4) (MTX + GA) group (MTX: 20 mg/kg, IP and gallic acid: 30 mg/kg/day, orally). Then amounts of malondialdehyde (MDA), nitric oxide (NO), glutathione peroxidase (GPx), glutathione (GSH), superoxide dismutase (SOD), interleukin 2 (IL-2) and interleukin 6 (IL-6) were analyzed in serum samples and then the histopathological examinations of the duodenum and jejunum of animals groups. Results: The results showed that treatment with GA significantly reduced the MTX-induced elevation of serum MDA (P < 0.001), NO (P < 0.001), IL-2 (P < 0.001) and IL-6 (P < 0.001) contents and increased MTX-induced reduction in GSH (P < 0.001) content, GPx (P < 0.001) and SOD (P < 0.001) activity. In addition, the histopathological results showed that MTX leads to intestinal tissue damage, and gallic acid can remarkably improve the pathological changes. Conclusions: Our results indicate that gallic acid can mitigate oxidative stress and pro-inflammatory parameters and also moderately prevent histopathological damage of the small intestine of rats exposed to MTX.