Effects of cyclosporine and tacrolimus on the oxidative stress in cultured mesangial cells.

ABSTRACT

OBJECTIVES: Cyclosporine (CsA) and tacrolimus (Tac) are two primary immunosuppressive agents used for the prevention of graft rejection. However, their use is associated with significant side effects, most notably nephrotoxicity. The mechanisms of this toxicity are not fully understood, but they seem to be associated with increases in the production of oxygen free radicals (OFRs). This present work examined the effect of CsA and Tac on the production of OFRs in cultured rat renal mesangial cells (RMCs). METHODS: Varying concentrations of CsA and Tac (0 to 40 micromol/L) were added to RMCs and incubated for 60 minutes at 37 degrees C. The production of OFRs was evaluated by measuring the fluorescent product from the oxidation of an oxidant-sensitive 2', 7'-dichlorofluorescin. RESULTS: At 60 minutes, the relative fluorescence units (RFU) for OFRs production in RMCs exposure to CsA were increased by 2.5%, 11.5%, 22.5%, 57.2%, and 174% at 2.5, 5, 10, 20, and 40 micromol/L, respectively. Tac increased the RFU by 15.9%, 13.6%, 14.8%, 13.2%, 21.4%, 13.2%, and 28.1% at 0.1, 1, 2.5, 5, 10, 20, and 40 micromol/L, respectively. In RMCs, the RFU produced by CsA was higher than that by Tac. CONCLUSIONS: The results of this experiment suggest that CsA and Tac induced renal injury by OFRs.