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

Abstract

Platinosis with severe dermatitis and/or asthma is 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. Thus, an accidental exposure to soluble platinum at a high dose in platinum refineries and pharmaceutical factories could induce occupational nephrotoxicity. Urinary citrate is freely filtered at the glomerulus, and its reabsorption in the proximal tubule is the major determinant of the rate of renal excretion. In our previous studies, we found that the preincubation of rat renal brush border membrane vesicles (BBMV) with cisplatin and carboplatin, a second-generation platinum coordination complex, significantly inhibited the citrate uptake compared with that of the control BBMV. In this study, we performed in vivo experiments in cisplatin-intoxicated rats to elucidate the toxic mechanism of cisplatin. And our results showed that the citrate uptake was significantly inhibited in cisplatin-intoxicated rats at 1 min compared with that of control rats.