Cyclosporine A-induced Lipid Peroxidation in Rat Renal Microsomes and Effect on Glucose Uptake by Renal Brush Border Membrane Vesicles

Abstract

Nephrotoxicity is the most important side effect of cyclosporine A (CsA) treatment and has been well documented in patients and experimental animals (1). The nature of CsA-induced renal damage is complex and the precise mechanism is still unclear. Some possible pathogenetic mechanisms have already been investigated. There is convincing evidence that a direct CsA effect on tubular cell could also contribute to CsA nephrotoxicity (2). CsA is taken up by isolated proximal tubule segments in a rapid, time-dependent and saturable manner (3). A saturable binding of CsA to isolated rat renal brush border membranes was also shown. This binding may be best explained by a partitioning process of the lipophilic CsA into the phospholipid phase of the cell membrane rather than binding to a specific membrane component. These findings demonstrate that CsA has the ability to interact with renal tubular cell membranes, even at low concentrations, and therefore has a distinct potential for toxic effects on renal cells. The aim of the present study was to investigate in vitro whether or not CsA induces lipid peroxidation in isolated rat renal microsomes and moreover to evaluate the influence of CsA on glucose uptake by rat renal brush border membrane vesicles. To the best of our knowledge there appeared only one report regarding to CsA-induced nephrotoxicity and lipid peroxidation.