Comparative nephrotoxic effects of cis-platinum (II), cis-palladium (II), and cis-rhodium (III) metal coordination compounds in rat kidneys

Abstract

A Sprague-Dawley rat kidney perfusion technique was used in situ to study the effects of cisdichloro-diamine platinum, PdCl 2 (2,6-diaminopyridine), and RhCl 3 (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 ≅ 45% decrease and ≅117% increase in Na + and Ca 2+ retention, respectively. Perfusates containing the coordination compounds in addition to 15 mM ouabain showed ≅76% decrease in Na + and insignificant increase in renal Ca 2+ 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 Ca 2+ 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 +-Ca 2+ symporter was insignificant.