Alterations of glutathione levels and related enzyme activities in non-tumourous rat liver cells after long-term treatment with adriamycin and/or cyclosporine A

In this work, we have treated rats with adriamycin and/or cyclosporine A du ring the 3 weeks of liver regeneration after partial hepatectomy. The proto col mimics a treatment protocol of patients with hepatocellular carcinoma b ased on liver transplantation. Our results indicate that adriamycin increas es the depletion of glutathione with time of treatment and that cyclosporin e A potentiate this effect by further decreasing the intracellular levels o f reduced glutathione. Compensatory alterations of activities of glutathion e dependent enzymes are also noted during treatment. It is reasonable to as sume that these effects on normal hepatocytes will increase the toxicity of the compounds with time. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.