Norouzirad Reza, Zahedi Khashayar, Behvandi Mohammad Mehdi, Moridnia Abbas, Sabbagh Susan
Department of Biochemistry, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran.
Student Research Committee, Dezful University of Medical Sciences, Dezful, Iran.
J Toxicol. 2025 Mar 17;2025:9990692. doi: 10.1155/jt/9990692. eCollection 2025.
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. 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. Decreased levels of HGF and C-met gene expression in the MTX group were significantly increased by GA administration ( < 0.05). GA administration decreased the elevated levels of TNF-α and IL-1β ( < 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. 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.
胃肠道黏膜炎（GI-M）是甲氨蝶呤（MTX）最常见的不良反应。没食子酸（GA）是一种富含于绿茶、五倍子、啤酒花、葡萄和橡木树皮中的多酚成分，具有抗炎和抗氧化特性。本研究旨在探讨GA对MTX诱导的大鼠GI-M中促炎细胞因子、肝细胞生长因子（HGF）和C-met基因表达水平以及组织病理学改变的影响。将24只雄性Wistar大鼠随机分为四组：对照组、GA组、MTX组和MTX+GA组。通过在肩胛上区域皮内注射（第3至5天）2.5mg/kg MTX诱导实验组（MTX组和MTX+GA组）发生黏膜炎。GA组通过灌胃给予100mg/kg GA，而对照组通过灌胃（连续7天）和在肩胛上区域皮内注射（第3至5天）给予生理盐水。分析空肠组织和血清中HGF和C-met mRNA表达以及肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）水平。此外，进行组织病理学研究以评估黏膜绒毛和黏膜下层纤维化情况。GA给药显著增加了MTX组中降低的HGF和C-met基因表达水平（P<0.05）。GA给药降低了MTX组中升高的TNF-α和IL-1β水平（P<0.001）。组织病理学结果显示MTX对黏膜有不良影响，而在MTX+GA组中相对改善。GA可增加HGF和C-met表达，降低炎性细胞因子，并改善受MTX影响的组织学损伤，表明GA在GI-M后具有有益作用。
