Authors: Jacob, M.¹; Bjarnason, I.²; Rafi, S.³; Wrigglesworth, J.⁴; Simpson, R. J.²

Source: Alimentary Pharmacology & Therapeutics, Volume 15, Number 11, November 2001 , pp. 1837-1842(6)

Publisher: Wiley-Blackwell

Abstract:

Background: 

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. Aim: 

To study the effect of indometacin on isolated liver mitochondria from rats, mice and humans. 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. 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). 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.

Document Type: Research article

Affiliations: 1: Department of Biochemistry, Christian Medical College, Vellore, India 2: Department of Endocrinology, Diabetes and Internal Medicine, Guy's, King's and St. Thomas's School of Medicine, London, UK 3: Department of Clinical Biochemistry, Guy's, King's and St. Thomas's School of Medicine, London, UK 4: Division of Life Sciences, King's College London, London, UK

Publication date: 2001-11-01

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• In this Subject: Pathology ,  Pharmacology ,  Surgery ,  Therapeutics & Alternative Medicine
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