Cyclosporine A induced lipid peroxidation in microsomes and effect on active and passive glucose transport by brush border membrane vesicles of rat kidney.

Abstract

The in vitro effect of cyclosporine A (CsA) on lipid peroxidation (LPO) in rat renal microsomes were investigated either with different CsA concentrations (0.001 to 1.5 mg/ml) or for different periods of time (0.5 to 3 h). Furthermore the influence of this drug on glucose uptake by rat renal brush border membrane vesicles (RBBMV) prepared from renal cortical slices which were preincubated with CsA for 1 or 3 h was studied. CsA caused a time- and concentration-dependent increase of malondialdehyde production in renal microsomes. LPO was inhibited by addition of the radical scavenger alpha-tocopherol. Regarding the CsA effect on the vesicular glucose uptake, an increase in the passive influx constants of L-glucose and a decrease in the maximal transport rates of the sodium-dependent D-glucose uptake were found as compared to the corresponding control values. The apparent affinities of D-glucose to the glucose transporter were slightly lowered after incubation of slices in a CsA containing medium. The results of the present study suggest that CsA causes LPO in renal microsomes and that this LPO is due to membrane damage by CsA as shown by alternations of active and passive glucose uptake by RBBMV.