Oxidative Stress Indices in Rats Under Immunosuppression

Abstract

Immunosuppressants lead to generation of reactive oxygen species (ROS). Oxidative stress (OxS) can initiate chronic allograft nephropathy (CAN). The most active antioxidant enzymes, superoxide dysmutase (SOD) and catalase (CAT), are present in erythrocytes. Glutathione peroxidase (GPx) is produced in the proximal tubules of nephrons. Malonyldialdehyde (MDA) concentrations are a marker of OxS intensity in plasma. In vitro and animal model studies have shown increased or decreased OxS during treatment with tacrolimus (Tac) or cyclosporine (CyA). Results obtained in humans after solid organ transplantation have been contradictory, because of confounding factors such as ischemia-reperfusion injury, donor and recipient ages, endothelial injury, and comorbidity. The aim of this study was to assess the intensity of OxS among rats under chronic immunosuppression (IS) without a transplantation. We examined 49 male Wistar rats. IS started at 12 weeks of age was continued for 6 months: group I were controls (n = 7); group II, Tac + sirolimus (Rapamycin [Rapa]) + corticosteroids (CS; n = 6); group III, CyA + Rapa + CS (n = 4 of which 2 died); group IV, Rapa + mycophenolate mofetil (MMF) + CS (n = 6); group V, CyA + MMF + CS (n = 6); group VI, CsA + MMF + CS for 3 months followed by conversion to Rapa (n = 6); group VII, Tac + MMF + CS (n = 6 rats); and group VIII, Tac + MMF + CS for 3 months followed by conversion to Rapa (n = 6). The drug doses were as follows: Tac 4 mg/kg/d; MMF 20 mg/kg/d; CyA 5mg/kg/d; Rapa 0.5mg/kg/d; and CS 4 mg/kg/d. Multiple regression analysis revealed that all IS drugs decreased GPx activity ( P < .001) except CS, which increased it ( P < .0001). Multiple regression analysis showed that CsA and Tac decreased plasma MDA concentrations ( P < .01), whereas CS increased them ( P < .05). In conclusion, all IS drugs except CS damage proximal tubules of nephrons.