Effect of L-arginine on methotrexate induced hepatotoxicity in albino rats.

Document Type : Original Article

Authors

1 Histochemistry and Cell Biology Department, Medical Research Institute Alexandria University

2 Pharmacology and Toxicology Department Faculty of Pharmacy (Girls), Al- Azhar University

Abstract

Methotrexate (MTX) is commonly used in the treatment of many different types of cancer and inflammatory diseases. Its cytotoxic nature also lends a substantial risk of life-threatening side effects. L-arginine is beneficial in the treatment of hepatic injury, hepatic cirrhosis and fatty liver degeneration. The present work aims to study the effect of L-arginine on hepatotoxicity of methotrexate in albino rats. Five groups of albino rats were used. Group I: control. Group II: rats were administered (MTX) in a daily oral dose of 0.45 mg/kg, for 28 days. Group III: rats were administered L-arginine in a daily oral dose of 300 mg/kg, for 28 days. Group IV: rats were received L- arginine 2 hrs before (MTX). Group V: rats were received L-arginine 2 hrs after (MTX). The results revealed different histopathological changes in liver of MTX-treated rats such as focal areas of necrosis and increased numbers of activated Kupffer cells, an apparent increase in the amount of collagen fibers and strong immunoreactive expression of α- SMA. Biochemical results revealed a significant increase in the serum levels of ALT, AST, bilirubin and decreasing the level of antioxidant enzymes. L-agrinine minimized the hepatotoxicity of MTX by decreasing the level of ALT, AST and bilirubin, MDA and increasing the antioxidant enzymes. It is concluded that L-arginine protects liver from hepatotoxicity of methotrexate and this due to its antioxidant activity.

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