OXIDATIVE STRESS IN CYCLOSPORINE AND AZATHIOPRINE TREATED RENAL-TRANSPLANT PATIENTS

The major cause of death following transplantation is cardiovascular d isease, 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 reg ime 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 substance s, TEARS), 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 usin g the fluorescent probe 1,6 diphenyl-1,3,5-hexatriene (DPH). Both tran splant groups showed no difference in TEARS, lipid standardised vitami n E, copper or selenium compared to controls. Zinc was significantly i ncreased in both the cyclosporin and azathioprine groups compared to c ontrols (P < 0.05), SOD was reduced in both transplant groups compared to controls (P < 0.001), GSHPx was elevated in both groups compared t o controls but only reached significance in the azathioprine treated g roup (P < 0.005), GSHRx was slightly elevated in both transplant group s but did not reach significance. Erythrocyte membrane anisotropy was decreased in the cyclosporin treated group (P < 0.05). There was no di fference in the azathioprine group compared to controls. The present r esults suggest an adaptive response to increased oxidative stress in b oth transplant groups sufficient to minimise markers of oxidative stre ss (TEARS and anisotropy). The results also suggest no significant dif ference between the two immunosuppressive regimes with regard to oxida tive stress. (C) 1997 Elsevier Science B.V.