Ibuprofen-induced liver mitochondrial permeability transition.
This study examined the effect of the nonsteroidal anti-inflammatory drug ibuprofen on liver inner mitochondrial membrane permeability transition in the presence of Ca2+ and phosphate. Incubation of isolated liver mitochondria with ibuprofen (0.1-0.4 mM) induced inner mitochondrial membrane permeability as indicated by loss of inner mitochondrial membrane potential, swelling of matrix and loss of pre-accumulated Ca2+. The presence of cyclosporin A (1 microM) in the incubation medium preventing ibuprofen from causing loss of inner mitochondrial membrane potential, swelling and loss of pre-accumulated Ca2+. It is concluded that ibuprofen acted as an activator of Ca2+ and phosphate in promoting the opening of inner mitochondrial membrane pore.
Al-Nasser
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IA
Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia. alnasser@kacst.edu.sa
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D016572:Cyclosporine / Q000633:toxicity; D007052:Ibuprofen / Q000633:toxicity*; D007166:Immunosuppressive Agents / Q000633:toxicity; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D007202:Indicators and Reagents; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D016572:Cyclosporine; D002118:Calcium; C013289:tetraphenylphosphonium; D007052:Ibuprofen