Nitric oxide protects the intestine from the damage induced by laparotomy and gut manipulation

Abstract

Background: The intestine is highly susceptible to free radical-induced damage, and our earlier work has shown that surgical stress induces the generation of oxygen free radicals in enterocytes, resulting in intestinal damage along with ultrastructural changes. Since nitric oxide (NO) is an important mediator of gastrointestinal function, this study looked at the effect of NO on surgical stress-induced intestinal alterations. Materials and methods: Control rats and rats pretreated with the NO donor l-arginine were subjected to surgical stress by opening the abdominal wall and handling the intestine as done during laparotomy. Enterocytes were isolated and homogenate prepared, and the protection offered by l-arginine against damage due to surgical stress was determined and compared with normal controls. Protection to structural as well as functional aspects of the intestine was also examined. Results: Intestinal manipulation affected intestinal structure as assessed by electron microscopy. Functional impairment of the enterocyte was also evident, with increased xanthine oxidase activity resulting in production of superoxide anion. This impairment is more dramatic in the crypt cells. Increased protease activity was also seen following laparotomy and handling. Pretreatment with the NO synthase substrate l-arginine prevented these damaging effects. Arginine protection was abolished in the presence of the NO synthase inhibitor NG-nitro-l-arginine methyl ester, indicating the role of NO. Conclusion: Stress in the small intestine due to any surgery can affect enterocyte structure and function. These damaging effects can be prevented by NO, an important modulator of cellular function.