Salicylate-induced kidney mitochondrial permeability transition is prevented by cyclosporin A.
The effect of salicylate, the active metabolite of aspirin (acetyl salicylic acid) in the presence of Ca2+ and phosphate on mitochondrial permeability transition (MPT) was studied. MPT is often associated with opening of a Ca2+ -induced pore. The opening of this pore leads to swelling, loss of mitochondrial membrane potential and release of accumulated Ca2+. In freshly isolated rat kidney mitochondria, salicylate (400 microM) in the presence of 20 nmol Ca2+/mg protein and 0.1 mM phosphate induced swelling, loss of mitochondrial membrane potential and release of accumulated Ca2+. All these changes were eliminated when cyclosporin A (1 microM), (a pore inhibitory agent) was included in the incubation medium. Unlike salicylate, unhydrolyzed aspirin (400 microM) induced these changes slightly. We concluded that salicylate acts as an activator of Ca2+ and phosphate in promoting the opening of kidney inner mitochondrial membrane pore. As a result a great consideration should be given to its toxicological effect.
Al-Nasser
I A
IA
Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000037:antagonists & inhibitors / Q000633:toxicity; D001241:Aspirin / Q000037:antagonists & inhibitors / Q000633:toxicity; D002118:Calcium / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D020156:Salicylic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020156:Salicylic Acid; D001241:Aspirin; D002118:Calcium