ISSN:
1365-2036
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
A part of the mechanism of the gastrointestinal toxicity exhibited by non-steroidal anti-inflammatory drugs is believed to involve the uncoupling of mitochondrial oxidative phosphorylation. Most previous uncoupling studies have used rat liver mitochondria. There is little information on the effects of the drugs on mitochondria from other species.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To study the effect of indometacin on isolated liver mitochondria from rats, mice and humans.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:We studied the effects of indometacin on respiration and adenosine triphosphate synthesis by isolated liver mitochondria from rats, mice and humans. Its effects were compared with those of dinitrophenol, a classical uncoupler.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Indometacin uncoupled oxidative phosphorylation at low concentrations (P 〈 0.05) and inhibited respiration at high concentrations (P 〈 0.01) in all three species. Adenosine triphosphate synthesis was, however, more sensitive to dinitrophenol or indometacin at lower concentrations in mouse and human compared to rat liver mitochondria (P 〈 0.05).〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:The current study shows that indometacin acts as an inhibitory uncoupler in human mitochondria. It also demonstrates that the responses of rat, mouse and human mitochondria to indometacin are broadly similar.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1365-2036.2001.01095.x
