Ibuprofen-induced liver mitochondrial permeability transition

被引:27
作者
Al-Nasser, IA [1 ]
机构
[1] King Saud Univ, Coll Sci, Dept Biochem, Riyadh 11451, Saudi Arabia
关键词
ibuprofen; hepatotoxicity; mitochondria; cyclosporin A;
D O I
10.1016/S0378-4274(99)00180-0
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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.
引用
收藏
页码:213 / 218
页数:6
相关论文
共 29 条
[1]  
ADAMS SS, 1970, RHEUMATOL PHYS MED S, V9, P9
[2]   Salicylate-induced kidney mitochondrial permeability transition is prevented by cyclosporin A [J].
Al-Nasser, IA .
TOXICOLOGY LETTERS, 1999, 105 (01) :1-8
[3]   THE REVERSIBLE CA-2+-INDUCED PERMEABILIZATION OF RAT-LIVER MITOCHONDRIA [J].
ALNASSER, I ;
CROMPTON, M .
BIOCHEMICAL JOURNAL, 1986, 239 (01) :19-29
[4]  
ALNASSER IA, 1993, MED SCI RES, V21, P777
[5]   EVIDENCE FOR THE INVOLVEMENT OF A MEMBRANE-ASSOCIATED CYCLOSPORINE-A-BINDING PROTEIN IN THE CA2+-ACTIVATED INNER MEMBRANE PORE OF HEART-MITOCHONDRIA [J].
ANDREEVA, L ;
TANVEER, A ;
CROMPTON, M .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1995, 230 (03) :1125-1132
[6]  
BERNARDI P, 1996, J BIOENERG BIOMEMBR, V24, P77
[7]   UPDATE ON IBUPROFEN - REVIEW ARTICLE [J].
BUSSON, M .
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH, 1986, 14 (02) :53-62
[8]   DISPOSITION AND COVALENT BINDING OF IBUPROFEN AND ITS ACYL GLUCURONIDE IN THE ELDERLY [J].
CASTILLO, M ;
LAM, YWF ;
DOOLEY, MA ;
STAHL, E ;
SMITH, PC .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1995, 57 (06) :636-644
[9]   PHARMACOKINETIC MODELING OF IBUPROFEN [J].
COLLIER, PS ;
DARCY, PF ;
HARRON, DWG ;
MORROW, N .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1978, 5 (06) :528-530
[10]   ACUTE-POISONING WITH IBUPROFEN [J].
COURT, H ;
STREETE, P ;
VOLANS, GN .
HUMAN TOXICOLOGY, 1983, 2 (02) :381-384