Mitigation of Methotrexate-Induced Intestinal Mucositis in Male Wistar Rats by Gallic Acid: The Role of HGF and C-Met Genes.

Abstract

Purpose: Gastrointestinal mucositis (GI-M) is the most common adverse effect of methotrexate (MTX). Gallic acid (GA) is a polyphenolic component rich in green tea, gall nuts, hops, grapes, and oak bark and has anti-inflammatory and antioxidant properties. The aim was to investigate the impact of GA on proinflammatory cytokines, expression level of hepatocyte growth factor (HGF) and C-met genes, and histopathological alterations of MTX-induced GI-M in rats. Methods: Twenty-four male Wistar rats were randomly divided into four groups: control, GA, MTX, and MTX + GA. Mucositis was induced in the experimental groups (MTX and MTX + GA) through three intradermal injections (the third to fifth days) of 2.5 mg/kg MTX in the suprascapular region. The GA group received 100 mg/kg GA via gavage, while the control group received normal saline by gavage (7 continuous days) and via intradermal injection (the third to fifth days) in the suprascapular region. The intestinal jejunal tissue and serum were analyzed for HGF and C-met mRNA expression, as well as levels of tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β). In addition, a histopathological study was to eperformedvaluate the villi of mucosa and fibrosis of submucosal layers. Results: Decreased levels of HGF and C-met gene expression in the MTX group were significantly increased by GA administration (p < 0.05). GA administration decreased the elevated levels of TNF-α and IL-1β (p < 0.001) in the MTX group. Histopathological findings showed an adverse effect of MTX in mucosa which was relatively ameliorated in the MTX + GA ones. Conclusion: GA could increase HGF and C-met expression, decrease inflammatory cytokines, and improve histological injuries, affected by MTX, indicating a beneficial role for GA following GI-M.