Oxidative stress in cyclosporin and azathioprine treated renal transplant patients

Abstract

The major cause of death following transplantation is cardiovascular disease. Among the many processes involved in atherogenesis, oxidative stress and modification of low density lipoprotein has been assigned a major role. This in turn may be affected by the immunosuppressive regime used. We studied oxidative stress in 40 renal transplant patients receiving two different immunosuppressive regimens (20 on cyclosporin, 20 on azathioprine/prednisolone), and 19 normal controls. Changes in lipid peroxidation (assessed as thiobarbituric acid reacting substances, TBARS), antioxidant enzyme activities (glutathione reductase GSHPx, glutathione peroxidase GSHPx and superoxide dismutase SOD) vitamin E and antioxidant associated trace metals (selenium, copper, zinc) were studied. Alteration of erythrocyte membrane fluidity was examined using the fluorescent probe 1,6 diphenyl-1,3,5-hexatriene (DPH). Both transplant groups showed no difference in TBARS, lipid standardised vitamin E, copper or selenium compared to controls. Zinc was significantly increased in both the cyclosporin and azathioprine groups compared to controls (P<0.05). SOD was reduced in both transplant groups compared to controls (P<0.001). GSHPx was elevated in both groups compared to controls but only reached significance in the azathioprine treated group (P<0.005). GSHRx was slightly elevated in both transplant groups but did not reach significance. Erythrocyte membrane anisotropy was decreased in the cyclosporin treated group (P<0.05). There was no difference in the azathioprine group compared to controls. The present results suggest an adaptive response to increased oxidative stress in both transplant groups sufficient to minimise markers of oxidative stress (TBARS and anisotropy). The results also suggest no significant difference between the two immunosuppressive regimes with regard to oxidative stress.