The role of eicosanoids in the process of adaptation following massive bowel resection in the rat.

Abstract

Long chain polyunsaturated fatty acids (LCPUFAs) such as arachidonic acid (AA) and eicosapentaenoic acid (EPA) stimulate intestinal adaptation. Prostaglandins also enhance intestinal adaptation. The purpose of this study was to determine by which eicosanoid pathway dietary arachidonic acid enhances intestinal adaptation. Cyclo-oxygenase or lipoxygenase were selectively inhibited to determine whether either of them enhanced or inhibited adaptation. Sixty Sprague-Dawley rats were divided into 2 groups, one receiving an 80% small bowel resection and the other receiving a sham operation. Rats were further divided into groups receiving either a placebo, a general lipoxygenase inhibitor (nordihydroguaiaretic acid [NDGA] at 40 mg/kg per day), or a cyclo-oxygenase-2 inhibitor (Etodolac at 3 mg/kg per day). Rats were pair-fed a diet containing 30% kcal from fat, primarily consisting of AA. After 14 days, mucosal mass, protein, DNA, and disaccharidase activity were measured in the remaining small intestine. There was a significant decrease in ileal mucosal mass in rats receiving Etodolac and a significant increase in mucosal mass in the duodenum in rats receiving NDGA (both p < .001). Mucosal DNA, protein, and disaccharidase data showed similar trends. These findings suggest that after small bowel resection, dietary arachidonic acid may facilitate the adaptation process by acting as a substrate for the synthesis of prostaglandins, and not through the derivatives of lipoxygenase such as leukotrienes or thromboxanes.