The use of NSAIDs (non-steroidal anti-inflammatory drugs), although of great therapeutic value clinically, is limited by their tendency to cause mucosal damage in the gastrointestinal tract. In the small intestine, the effects these drugs have been shown to produce include inhibition of cyclo-oxygenase, mitochondrial dysfunction and free radical-induced oxidative changes, all of which contribute to the mucosal damage seen. Glutamine is a fuel preferentially used by enterocytes and is known to contribute to maintaining the integrity of these cells. In the present study, we investigated the effect of glutamine on indomethacin-induced changes in the small intestinal mucosa. Rats were given 2% glutamine or glutamic acid or isonitrogenous amino acids, glycine or alanine, in the diet for 7 days. Indomethacin was then administered orally at a dose of 40 mg/kg of body weight. After 1 h, the small intestine was removed and used for the measurement of parameters of oxidative stress and mitochondrial and BBM (brush border membrane) function. Evidence of oxidative stress was found in the mucosa of the small intestine of drug-treated rats, as indicated by significantly increased activity of xanthine oxidase (P<0.001) and myeloperoxidase (P<0.001), with corresponding decreases in the levels of several free radical scavenging enzymes and α-tocopherol (P<0.001 in all cases). Levels of products of peroxidation were also significantly elevated (P<0.001 for all the parameters measured). In addition, oxidative stress was evident in isolated intestinal mitochondria and BBMs (P<0.001 for all the parameters measured), with associated alterations in function of these organelles (P<0.001 for all the parameters measured). Supplementation of the diet with glutamine or glutamic acid prior to treatment with indomethacin produced significant amelioration in all the effects produced by the drug in the small intestine (P<0.001 for all the parameters measured). Glycine and alanine were found to be much less effective in these respects.
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Research Article|
August 24 2004
Oral glutamine attenuates indomethacin-induced small intestinal damage
Jayasree BASIVIREDDY;
Jayasree BASIVIREDDY
*The Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, India
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Molly JACOB;
†Department of Biochemistry, Christian Medical College, Vellore 632002, India
Correspondence: Dr Molly Jacob (email [email protected]).
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Kunissery A. BALASUBRAMANIAN
Kunissery A. BALASUBRAMANIAN
*The Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, India
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Publisher: Portland Press Ltd
Received:
November 27 2003
Revision Received:
March 10 2004
Accepted:
May 06 2004
Accepted Manuscript online:
May 06 2004
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2004
Clin Sci (Lond) (2004) 107 (3): 281–289.
Article history
Received:
November 27 2003
Revision Received:
March 10 2004
Accepted:
May 06 2004
Accepted Manuscript online:
May 06 2004
Citation
Jayasree BASIVIREDDY, Molly JACOB, Kunissery A. BALASUBRAMANIAN; Oral glutamine attenuates indomethacin-induced small intestinal damage. Clin Sci (Lond) 1 September 2004; 107 (3): 281–289. doi: https://doi.org/10.1042/CS20030390
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