Application of garlic organosulfur compounds in prevention of cyclosporine A-induced hepatotoxicity

Abstract

Cyclosporine A (CsA) is a powerful immunosuppressant drug most widely used in management of organ transplantation and autoimmune diseases. However, in therapeutic doses CsA induces several side effects including renal and liver toxicity. CsA induced hepatotoxicity usually occurs in the first 90 post-transplant days and can limit its therapeutic use. Cumulative data showed that oxidative stress induced by reactive oxygen species (ROS) over production and compromised antioxidant capacity play an important role in the development of hepatotoxicity in CsA treated patients. CsA induced oxidative stress decreases hepatocyte reduced glutathione (GSH) and impairs the function of its related enzymes. Consequently any mechanism which removes ROS or prevents hepatic GSH depletion or induce production of GSH dependent enzymes may provide protection for hepatotoxicity in CsA-treated patient. Garlic organosulfur compounds have been reported that enhance cellular antioxidant activity by radical scavenging abilities and augmentation of endogenous antioxidants via prevention of GSH depletion and increasing of GSH dependent enzymes activity and their gene expression. Based on these facts we propose the hypothesis that garlic organosulfur compounds can prevent CsA hepatotoxicity. Before clinical use further investigations in animal models are needed.