Effect of Platinum Coordination Complex (PtCx) onCitrate Uptake by Rat Renal Brush Border Membrane Vesicles (BBMV): Cisplatin-Intoxicated Rats

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Platinosis with severe dermatitis and/or asthma is broadly defined as the effects of solubleplatinum salts on people exposed to them occupationally. Platinum coordination complexes arewidely used in the treatment of a variety of solid tumors. However, the clinical use of cisplatin, themost useful agent, is limited by the development of nephrotoxicity. Thus, an accidental exposure tosoluble platinum at a high dose in platinum refineries and pharmaceutical factories could induceoccupational nephrotoxicity. Urinary citrate is freely filtered at the glomerulus, and its reabsorptionin the proximal tubule is the major determinant of the rate of renal excretion. In our previousstudies, we found that the preincubation of rat renal brush border membrane vesicles (BBMV) withcisplatin and carboplatin, a second-generation platinum coordination complex, significantly inhibitedthe citrate uptake compared with that of the control BBMV. In this study, we performed in vivoexpriments in cisplatin-intoxicated rats to elucidate the toxic mechanism of cisplatin. And our resultsshowed that the citrate uptake was significantly inhibited in cisplatin-intoxicated rats at 1 min compared with that of control rats.
独立行政法人労働安全衛生総合研究所の論文