Comparative nephrotoxic effects of cis-platinum (II), cis-palladium (II), and cis-rhodium (III) metal coordination compounds in rat kidneys.
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.
Bikhazi
A B
AB
Department of Physiology, American University of Beirut, New York, NY 10022, USA.
Salameh
A
A
el-Kasti
M M
MM
Awar
R A
RA
D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D010042:Ouabain / Q000008:administration & dosage / Q000494:pharmacology; D010165:Palladium / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012238:Rhodium / Q000008:administration & dosage / Q000633:toxicity*; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D015220:Calcium Channels; D017923:Sodium-Hydrogen Exchangers; D010042:Ouabain; D010165:Palladium; D012964:Sodium; D012238:Rhodium; D000254:Sodium-Potassium-Exchanging ATPase; D002945:Cisplatin; D002118:Calcium