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

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.

The present study aimed to assess the effect of gallic acid (GA) against MTX-induced intestinal mucositis in male Wistar rats.

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.

The results showed that treatment with GA significantly reduced the MTX-induced elevation of serumMDA(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.

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.