Thesis (M.Sc.) - Cairo University - Faculty of Medicine - Department of Histology

Background: Hepatic injury, a common complication of methotrexate (MTX) therapy, is followed by fibrosis. Activated hepatic stellate cells (HSCs) are responsible for such fibrosis. Folic acid (FA) reduces the incidence of MTX-liver toxicity meanwhile natural antioxidants are used without interfering the effectiveness. Aim of work: The study aimed at comparing the possible protective effect of grape seeds extract (GSE) and FA in a rat model of MTX-induced liver injury with a special reference on their influence on HSCs. Materials and methods: Thirty five adult male albino rats were divided into control, MTX, MTX-FA and MTX-GSE groups. Liver sections were stained with H&E, trichrome stain and immunohistochemical staining for Ü-smooth muscle actin (Ü-SMA) and glial fibrillary acidic protein (GFAP). Morphometric measurements of mean area percent of collagen fibers, Ü-SMA immune positive cells and GFAP immune positive cells were taken and statistically analyzed. Results: MTX group revealed marked with significant increase in the mean area percent of collagen, GFAP and Ü-SMA +ve cells. FA and GSE treated groups showed improvement in the hepatic lesions which was more obvious with GSE treatment. Conclusion: GSE had a better protective effect in reducing MTX-induced liver injury than FA

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