Methotrexate (MTX) is widely used in treatment of malignant tumors and autoimmune diseases. Gastrointestinal toxicity is an important factor limiting its use. This study was performed to assess the possible protective effect of ginger on MTX- induced intestinal damage and the mechanisms involved. Forty adult rats were randomly assigned into 4 groups: control group, ginger group (200 mg/kg/d, orally), MTX group (single dose, 20 mg/kg/ i.p.) and MTX+ ginger group (pretreated with ginger 3 days before and after MTX administration). At the end of the treatment period, rats were sacrificed, and jejunal tissue samples were taken for biochemical, histological and immunohistochemical assessment. Data showed that ginger produced significant decrease in lipid peroxidation product malondialdehyde (MDA) with significant increase in glutathione content (GSH), and antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) levels compared to MTX group. Also, pretreatment with ginger resulted in significant decrease in intestinal levels of myeloperoxidase (MPO) and pro-inflammatory cytokines (TNF-α and IL-1ß) levels. The total microscopic damage score of MTX + ginger-treated rats was found to be significantly reduced compared to the MTX group. Additionally, a significant decrease in enterocyte apoptosis in the jejunum of MTX+ ginger rats was accompanied by decreased Bax protein and increased Bcl-2 protein expression. The results of this study demonstrated that administration of ginger powder protects the jejunal mucosa from damage caused by MTX. Ginger was shown to reduce oxidative stress and lessen inflammation and apoptosis in the jejunal tissues of rats with MTX- induced mucositis. |
