Sulfhydryl blocker-induced rat colonic inflammation is ameliorated by inhibition of nitric oxide synthase

Gastroenterology. 1995 Jul;109(1):98-106. doi: 10.1016/0016-5085(95)90273-2.


Background & aims: Sulfhydryl compounds are essential in maintaining mucosal integrity, and nitric oxide may contribute to tissue injury. The aim of this study was to characterize experimental colitis induced by a sulfhydryl blocker.

Methods: Colitis was induced in rats by intracolonic administration of 0.1 mL 3% iodoacetamide with and without addition of 0.1 mg/mL NG-nitro-L-arginine methyl ester (L-NAME) to the drinking water. After death, the distal colonic segment was resected and weighed, and mucosal inflammatory mediator, myeloperoxidase, and NO synthase activities were determined.

Results: Iodoacetamide induced multifocal mucosal erosions and ulceration that were present for up to 1 week. At 3 weeks, the mucosa was almost intact. Colonic wet weight was maximal at 7 days. Myeloperoxidase activity and NO generation were increased in the first 72 hours, and NO synthase activity and prostaglandin E2 generation were increased up to 21 days. Leukotriene B4 and leukotriene C4 generation were increased up to 14 days. One week after iodoacetamide plus L-NAME treatment, lesion area was reduced by 85% and NO synthase activity by 52%.

Conclusions: Inflammatory mediators have an important contribution to the pathogenesis of colonic injury induced by a sulfhydryl alkylator. The protective effect of L-NAME indicates that NO contributes to tissue injury and that its modulation may be a novel approach to treat inflammatory bowel disease.

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors*
  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / pharmacology
  • Colitis / chemically induced
  • Colitis / metabolism
  • Colitis / prevention & control*
  • Colon / drug effects
  • Colon / metabolism
  • Colon / pathology
  • Dinoprostone / biosynthesis
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Iodoacetamide / adverse effects*
  • Leukotriene B4 / biosynthesis
  • Leukotriene C4 / biosynthesis
  • Male
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide / metabolism
  • Nitric Oxide / physiology
  • Nitric Oxide Synthase
  • Peroxidase / metabolism
  • Rats
  • Rats, Sprague-Dawley


  • Leukotriene B4
  • Leukotriene C4
  • Nitric Oxide
  • Arginine
  • Peroxidase
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • Dinoprostone
  • NG-Nitroarginine Methyl Ester
  • Iodoacetamide