4.5 Article

Ibuprofen-induced liver mitochondrial permeability transition

Journal

TOXICOLOGY LETTERS
Volume 111, Issue 3, Pages 213-218

Publisher

ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0378-4274(99)00180-0

Keywords

ibuprofen; hepatotoxicity; mitochondria; cyclosporin A

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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 mu M) 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. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.

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