Nitric oxide prevents intestinal mitochondrial dysfunction induced by surgical stress.
BACKGROUND
The intestine is highly susceptible to free radical-induced damage and earlier work has shown that surgical stress induces generation of oxygen free radicals in enterocytes, resulting in intestinal damage along with changes in mitochondrial structure and function. Nitric oxide is an important mediator of gastrointestinal function and this study looked at the effect of nitric oxide on surgical stress-induced intestinal mitochondrial alterations.


METHODS
Controls and rats pretreated with the nitric oxide donor L-arginine were subjected to surgical stress by opening the abdominal wall and handling the intestine. Enterocytes were isolated, mitochondria prepared and the protection offered by L-arginine against damage due to surgical stress was determined. Protection to structural as well as functional aspects of mitochondria was examined.


RESULTS
Mild handling of the intestine affected the enterocyte mitochondrial structure as assessed by lipid composition and electron microscopy. Mitochondria were also functionally impaired with altered calcium flux and decreased respiratory control ratio. Pretreatment with the nitric oxide synthase substrate L-arginine prevented these damaging effects of surgical stress. Protection with arginine was abolished by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, indicating the role of nitric oxide.


CONCLUSIONS
Surgical stress in the small intestine can affect enterocyte mitochondrial structure and function. These damaging effects can be prevented by nitric oxide, an important modulator of cellular function.
Thomas
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S
Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore-632004, India.
Anup
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R
Susama
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P
Balasubramanian
K A
KA
D000818:Animals; D005260:Female; D007410:Intestinal Diseases / Q000517:prevention & control*; D007421:Intestine, Small; D050356:Lipid Metabolism; D008297:Male; D008928:Mitochondria / Q000000981:diagnostic imaging; D017240:Mitochondrial Myopathies / Q000517:prevention & control*; D008933:Mitochondrial Swelling / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013048:Specimen Handling; D013312:Stress, Physiological / Q000517:prevention & control*; D014463:Ultrasonography
D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester