Miura K, Goldstein R S, Pasino D A, Hook J B
Toxicology. 1987 May;44(2):147-58. doi: 10.1016/0300-483x(87)90145-4.
Isolated perfused rat kidneys were used to determine the contribution of filtration and tubular transport of cisplatin to its nephrotoxicity. Perfusion of kidneys with 0.5 mM cisplatin concomitantly reduced tubular reabsorption of electrolytes and glomerular filtration rate in a time-dependent manner. These renal functional changes were similar to those obtained following in vivo cisplatin treatment (10 mg/kg). In vitro exposure to cisplatin reduced the renal clearance of organic ions without reducing renal perfusate flow, suggesting that renal hemodynamic changes do not mediate cisplatin-induced proximal tubular dysfunction. Inhibition of organic ion transport also was observed in non-filtering perfused kidneys treated with 0.5 mM cisplatin, implying that filtration of cisplatin is not a prerequisite for induction of toxicity. These data also suggest that cisplatin transport from a basolateral site may be important in the development of acute nephrotoxicity.
采用离体灌注大鼠肾脏来确定顺铂的滤过和肾小管转运对其肾毒性的影响。用0.5 mM顺铂灌注肾脏会随时间推移同时降低电解质的肾小管重吸收和肾小球滤过率。这些肾功能变化与体内给予顺铂（10 mg/kg）后所观察到的变化相似。体外暴露于顺铂会降低有机离子的肾清除率，而不降低肾灌注液流量，这表明肾血流动力学变化并非介导顺铂诱导的近端肾小管功能障碍的原因。在用0.5 mM顺铂处理的非滤过灌注肾脏中也观察到了有机离子转运的抑制，这意味着顺铂的滤过并非诱导毒性的必要条件。这些数据还表明，从基底外侧位点转运顺铂可能在急性肾毒性的发生中起重要作用。
