Effect of platinum coordination complex (PtCx) on citrate uptake by rat renal brush border membrane vesicles (BBMV): direct effect of cisplatin.

Abstract

Platinosis (severe dermatitis and/or asthma) may be broadly defined as the effects of soluble platinum salts on people exposed to them occupationally. Platinum coordination complexes are widely used in the treatment of a variety of solid tumors. However, the clinical use of cisplatin (the most useful agent) is limited by the development of nephrotoxicity. High dose exposure of soluble platinum could possibly induce nephrotoxicity, occupationally. Urinary citrate is freely filtered at the glomerulus, and its reabsorption in the proximal tubule is the major determinant of rate. In this study, we exposed isolated rat renal brush border membrane vesicles (BBMV) to cisplatin and examined their citrate uptake characteristics. BBMV were prepared by the divalent cation precipitation method. Citrate uptake was measured by the Millipore rapid membrane filtration technique. The preincubation of BBMV with 5 mM of cisplatin for 4 and 8 hours significantly inhibited citrate uptake compared with that of the control BBMV. These findings might contribute to nephrotoxicity in cisplatin therapy.