Effect of Platinum Coordination Complex (PtCx) onCitrate Uptake by Rat Renal Brush Border Membrane Vesicles (BBMV): Direct Effect of Carboplatin

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Inhalation of platinum, as soluble salts, is known to cause respiratory distress and severedermatitis in workers. Platinum coordination complexes are widely used in the treatment of a varietyof solid tumors. However, the clinical use of cisplatin (CDDP) (the most useful agent) is limited bythe development of nephrotoxicity. High dose accidental exposure to soluble platinum in platinumrefineries and pharmaceutical factories could induce occupational nephrotoxicity. Carboplatin(CBDCA), a second-generation platinum coordination complex, is highly effective against a varietyof malignancies at doses five- to ten-times higher than CDDP. At therapeutic doses, CBDCA is lessnephrotoxic than CDDP. Additionally, urinary citrate is freely filtered at the glomerulus, and itsreabsorption in the proximal tubule is the major determinant of the rate of renal excretion. In ourprevious study, the preincubation of rat renal brush border membrane vesicles (BBMV) with 5 mMcisplatin for 4 and 8 hours significantly inhibited the citrate uptake compared with that of the controlBBMV. In this study, we exposed BBMV to 100 mM carboplatin (twenty-times higher concentrationthan cisplatin) and examined the citrate uptake characteristics to clarify the toxic mechanism ofplatinum coordination complexes. The preincubation of BBMV with 100 mM carboplatin for 8hours also significantly inhibited the citrate uptake compared with that of the control BBMV, but the alterations were not as severe as those with 5 mM cisplatin.
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Effect of Platinum Coordination Complex (PtCx) onCitrate Uptake by Rat Renal Brush Border Membrane Vesicles (BBMV): Direct Effect of Carboplatin

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