Abstract

ARAUJO, Carmen Rosa; POSLEMAN, Sara Emilia  and  DE LA CRUZ RODRIGUEZ, Lilia Cristina. Changes in the antioxidant defence system induced by Cyclosporin A. Acta bioquím. clín. latinoam. [online]. 2007, vol.41, n.1, pp.35-45. ISSN 0325-2957.

Cyclosporin A (CyA), an immunosuppressive agent, exerts adverse effects such as hepatotoxicity. The effect of CyA on the Antioxidant Defence System(ADS), its relation to lipoperoxidation, and liver function were studied. Assays were performed on male wistar rats weighing 200-260 g during acute (7 days) and chronic (120 days) treatment with oral doses of CyA of 5 and 20 mg/kg/day. ADS was studied in rat liver homogenate by measuring the liver content of total glutathion (GSH), glutathion peroxidase(GPx) and catalase (CAT); the Liver Profile Test (LPT) was measured by determining aspartate amino transferase (AST), alanin amino transferase (ALT) and total bilirubin (TB), and lipoperoxidation by determining thiobarbituric acid reactive substances (TRAS). The results were confirmed by histological studies. In the acute treatment, 20 mg/kg/day with CyA, a significant increase in TRAS (30.51±1.97 nmol/g), a loss of GSH (2.47±0.06 µmol/g) and a significant increase in GPx (663.25±1.88 mU/mg) and CAT (290.65±3.31 mU/mg) were observed. In the chronic treatment, 5 mg/kg/day with CyA, a time-dependent decrease in the ADS with a diminution in GSH (3.19±0.05 µmol/g), GPx (569.6±2.67 mU/mg) and CAT (223.3±2.78 mU/mg) were observed, with no changes in TRAS. The results for the chronic and acute treatment with 20 mg/kg/day of CyA are coincident, only this dose causing alterations in liver parenchyma histoarchitecture. CyA doses of 20 mg/kg/day during acute and chronic treatment cause lipoperoxidation with ADS involvement and hepatocyte alteration. CyA doses of 5 mg/kg/day during chronic treatment cause deterioration in the ADS with no lipoperoxidation, hepatotoxicity being reversible. Immunosuppression in human patients with 3 to 8 mg/kg/day doses, would cause a decrease in the ADS with no structural or functional changes in the hepatocyte.

Keywords : cyclosporin A; antioxidant defence system; glutathion; glutathion peroxidase; catalase; lipoperoxidation.

        · abstract in Spanish     · text in Spanish     · Spanish ( pdf )