Non-steroidal anti-inflammatory drugs (NSAIDs) are known to cause enteropathy, but the mechanism by which this toxicity occurs is less well established. This paper sets out to test the hypothesis that these drugs affect oxidative phosphorylation in jejunal tissue, thereby interfering with energy metabolism and rendering the tissue vulnerable to damage. Jejunal tissue obtained from rats and humans was used for in vitro determinations of oxygen uptake, lactate production and energy charge levels in the presence of indomethacin, a commonly used NSAID. In the rat jejunal tissue, drug concentrations of 0.5mM and 2.5mM produced significant decreases in oxygen uptake (P < 0.01) and energy charge levels in the tissue (P < 0.05). There was a corresponding increase in lactate production by the tissue at these indomethacin concentrations (P < 0.05). Rat jejunum examined by electron microscopy after incubation with various concentrations of indomethacin showed ultrastructural effects of the drug on mitochondrial morphology. In human tissue, an inhibitory effect of indomethacin on oxygen uptake was seen, but the effects on lactate production and energy charge were less conclusive. These findings suggest that indomethacin affects mitochondria and thereby impairs energy metabolism in jejunal tissue.
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Research Article| September 25 2001
Effects of indomethacin on energy metabolism in rat and human jejunal tissue in vitro
Molly JACOB ;
Ingvar BJARNASON ;
Robert J. SIMPSON
1Department of Endocrinology, Diabetes and Internal Medicine, Guy's, King's and St. Thomas's School of Medicine, Bessemer Road, King's College, London SE5 9PJ, U.K.
Correspondence: Dr R. J. Simpson, Department of Endocrinology, Diabetes and Internal Medicine, King's College Denmark Hill Campus, Bessemer Rd, London SE5 9PJ, U.K. (e-mail firstname.lastname@example.org).
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Molly JACOB, Ingvar BJARNASON, Robert J. SIMPSON; Effects of indomethacin on energy metabolism in rat and human jejunal tissue in vitro. Clin Sci (Lond) 1 November 2001; 101 (5): 493–498. doi: https://doi.org/10.1042/cs1010493
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