Bikhazi A B, Salameh A, el-Kasti M M, Awar R A
Department of Physiology, American University of Beirut, New York, NY 10022, USA.
Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1995 Jul;111(3):423-7. doi: 10.1016/0742-8413(95)00069-0.
A Sprague-Dawley rat kidney perfusion technique was used in situ to study the effects of cis-dichloro-diamine platinum, PdCl2 (2,6-diaminopyridine), and RhCl3 (2,6-diaminopyridine) on sodium and calcium retention in the whole kidney. The technique involves perfusion of both kidneys via the abdominal aorta and then through the right and left renal arteries and dorsal aorta. Compared to controls, kidneys perfused independently with the three coordination compounds showed approximately equal to 45% decrease and approximately equal to 117% increase in Na+ and Ca2+ retention, respectively. Perfusates containing the coordination compounds in addition to 15 mM ouabain showed approximately equal to 76% decrease in Na+ and insignificant increase in renal Ca2+ retention. Hence, one can rule out the presence of voltage-gated Ca(2+)-channels at the basolateral side due to membrane depolarization. These results suggest that the three metal coordination compounds showed identical nephrotoxic effects on the handling of Na+ and Ca2+ ions by inhibiting both the Na(+)-Ca(2+)-anti-porter and the Na(+)-H(+)-exchanger with laxing effects on nonvoltage-gated Ca(2+)-channels at the basolateral side. However, their effects on the Na(+)-K(+)-ATPase and the Na(+)-Ca2+ symporter was insignificant.
采用原位Sprague-Dawley大鼠肾脏灌注技术，研究顺二氯二氨铂、PdCl2（2,6 - 二氨基吡啶）和RhCl3（2,6 - 二氨基吡啶）对全肾钠和钙潴留的影响。该技术包括通过腹主动脉，然后经左右肾动脉和背主动脉对双侧肾脏进行灌注。与对照组相比，用这三种配位化合物单独灌注的肾脏，钠潴留减少约45%，钙潴留增加约117%。除15 mM哇巴因外，含有配位化合物的灌注液使钠潴留减少约76%，肾脏钙潴留无显著增加。因此，可以排除由于膜去极化导致基底外侧存在电压门控Ca(2 +)通道。这些结果表明，这三种金属配位化合物通过抑制钠钙反向转运体和钠氢交换体，对基底外侧非电压门控Ca(2 +)通道有松弛作用，从而对钠和钙离子的处理表现出相同的肾毒性作用。然而，它们对钠钾ATP酶和钠钙同向转运体的影响不显著。
