Sumpio B E, Chaudry I H, Baue A E
J Surg Res. 1985 May;38(5):429-37. doi: 10.1016/0022-4804(85)90058-7.
cis-Diamminedichloroplatinum (CDDP), a widely used cancer chemotherapeutic agent, has been shown to cause dose-dependent acute renal failure (ARF) probably secondary to a direct nephrotoxic effect on proximal tubule cells. The aim of this study was to determine whether administration of ATP-MgCl2 could ameliorate the deleterious effects of CDDP. Isolated rat kidneys were perfused for 2 hr with a 3.5 g % dextran T-110-Krebs HCO3 solution containing 100 micrograms/ml of CDDP. [3H]Inulin was added to measure GFR. Trace amounts of 14C-methylated cytochrome c (cyt) were added to the perfusate to determine the protein reabsorptive capacity (a sensitive indicator of tubular damage) of isolated perfused rat kidneys. Cyt, inulin radioactivity, and [Na+] were measured in the perfusate and urine in control and CDDP-treated kidneys. In additional experiments, ATP-MgCl2 was added simultaneously (0.3 mM) or 1 hr (2 mM) after CDDP treatment. The results indicate that after 2 hr of perfusion, CDDP treatment led to a marked inhibition of protein reabsorption with only a minimal decrease in Na+ and H2O absorption. Furthermore, GFR was not significantly altered despite a marked diuresis. Post-treatment with ATP-MgCl2 led to partial alleviation of the nephrotoxic effect of CDDP after 1 hr of perfusion. ATP-MgCl2 treatment simultaneously with CDDP, however, fully protected the protein reabsorptive capacity of CDDP-treated kidneys. The potential for administering ATP-MgCl2 simultaneously with CDDP suggests a new therapeutic modality in preventing ARF due to CDDP therapy.
顺二氯二氨铂（CDDP）是一种广泛应用的癌症化疗药物，已被证明可导致剂量依赖性急性肾衰竭（ARF），这可能继发于对近端小管细胞的直接肾毒性作用。本研究的目的是确定给予ATP - MgCl₂是否能改善CDDP的有害影响。将分离的大鼠肾脏用含有100微克/毫升CDDP的3.5%右旋糖酐T - 110 - 克雷布斯碳酸氢盐溶液灌注2小时。加入[³H]菊粉以测量肾小球滤过率（GFR）。向灌注液中加入微量的¹⁴C - 甲基化细胞色素c（cyt），以确定分离的灌注大鼠肾脏的蛋白质重吸收能力（肾小管损伤的敏感指标）。在对照和CDDP处理的肾脏中，测量灌注液和尿液中的细胞色素c、菊粉放射性和[Na⁺]。在额外的实验中，在CDDP处理后同时（0.3 mM）或1小时后（2 mM）加入ATP - MgCl₂。结果表明，灌注2小时后，CDDP处理导致蛋白质重吸收显著抑制，而Na⁺和水的吸收仅略有下降。此外，尽管出现明显利尿，但GFR没有显著改变。灌注1小时后用ATP - MgCl₂进行后处理可部分减轻CDDP的肾毒性作用。然而，与CDDP同时给予ATP - MgCl₂可完全保护CDDP处理的肾脏的蛋白质重吸收能力。与CDDP同时给予ATP - MgCl₂的可能性提示了一种预防CDDP治疗所致ARF的新治疗方式。
