The non-steroidal anti-inflammatory drugs (NSAIDs) are a widely used group of drugs in clinical medicine. However, their propensity to cause gastrointestinal damage limits their clinical utility. The pathogenesis of this toxicity is not well established. It has been postulated that an early event in the development of damage is an effect of these drugs on mitochondrial function. The present paper sets out to evaluate the effects of indomethacin, a commonly used NSAID, on energy metabolism in vivo. Indomethacin was administered to male Sprague-Dawley rats, either intrajejunally or orally, and indices of mitochondrial function were determined. The parameters chosen for this purpose were oxygen uptake by, lactate levels in and the energy charge of jejunal tissue. Oxygen uptake by and energy charge in jejunal tissue were unaffected at 1 and 3h after dosing by gavage with indomethacin. The drug significantly affected the tissue lactate/pyruvate ratio at 3h (but not at 1h) after oral dosing. Effects of indomethacin on jejunum incubated ex vivo were found to be reversible. The data suggest that indomethacin affects mitochondrial function in vivo, but that compensatory changes in glycolytic rate maintain energy charge.
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May 2002
Research Article|
April 18 2002
Effects of indomethacin on energy metabolism in rat jejunal tissue in vivo
Molly JACOB
;
Molly JACOB
*Department of Biochemistry, Christian Medical College, Vellore, India 632002
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Ingvar BJARNASON
;
Ingvar BJARNASON
†Department of Endocrinology, Diabetes and Internal Medicine, Guy's, King's and St. Thomas's School of Medicine, Bessemer Road, London SE5 9PJ, U.K.
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Robert J. SIMPSON
†Department of Endocrinology, Diabetes and Internal Medicine, Guy's, King's and St. Thomas's School of Medicine, Bessemer Road, London SE5 9PJ, U.K.
Correspondence: Dr Robert J. Simpson (e-mail robert.simpson@kcl.ac.uk).
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Clin Sci (Lond) (2002) 102 (5): 541–546.
Article history
Accepted:
February 12 2001
Received:
September 17 2001
Revision Received:
December 03 2001
Citation
Molly JACOB, Ingvar BJARNASON, Robert J. SIMPSON; Effects of indomethacin on energy metabolism in rat jejunal tissue in vivo. Clin Sci (Lond) 1 May 2002; 102 (5): 541–546. doi: https://doi.org/10.1042/cs1020541
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