Effect of dietary arginine on the jejunal mucosa in indomethacin-induced intestinal injury: light and scanning electron microscopic study in male mice

ABSTRACT

The non-steroidal anti-inflammatory drug [NSAID] indomethacin causes, via its adverse effects, damage to the gastrointestinal mucosa of humans and experimental animals. The indomethacin-induced intestinal injury in mice jejunum is considered an experimental model of Crohn's disease, as one of the inflammatory bowel diseases [IBD's]. The semi-essential amino acid arginine, which is a precursor of nitric oxide, is proposed to promote gastrointestinal mucosal integrity. The present work aimed to study the possible protective role of dietary supplementation with arginine in ameliorating indomethacin-induced mucosal injury of mice jejunum. The present study was carried out on forty adult male mice which were divided into 4 equal groups; group I [negative control group] which received no treatment, group II [positive control]; mice received dietary L-arginine alone in a daily dose of 300 mg/Kg, group III [indomethacin group]; mice of this group received 2 consecutive subcutaneous injections of indomethacin in a dose of 7.5 mg/kg, 24 hours apart and group IV [arginine group]; in which arginine supplementation was provided 2 days before the administration of indomethacin, maintained during the administration and continued 3 days later till the end of the experiment. Mice of all groups were sacrificed by the end of the 7[th] day and specimens from the jejunum were dissected and processed for light and scanning electron microscopic examinations. Indomethacin-treated group exhibited jejunal mucosal injury. Light microscopic examination of this group, using H and E and toluidine blue- stained semithin sections showed distorted villi and sloughing of some of their apical parts with extrusion of many degenerated cells, intermingled with excess mucous. Some enterocytes appeared degenerated with loss of their regular arrangement, while the goblet cells appeared distended with excess mucous secretion. Increased cellular infiltration and edema of the villous core and in the lamina propria between the glands were noticed. Increased mucous secretion was also demonstrated by combined alcian blue-periodic acid Schiff reaction. Scanning electron microscope revealed alteration in the architecture of many villi which appeared short, blunt or with denuded surface and occasionally covered with membrane-like structure. The group of mice received arginine [group IV] revealed restoration of mucosal integrity in the form of regular villi with intact epithelial coverings including enterocytes and goblet cells. Some villi appeared shorter, while others showed partially denuded apical surface. Arginine evoked a remarkable cellular infiltration. Lymphocytes and macrophages were among the infiltrating cells and their roles were suggested to be vital in the healing process. Dietary L-arginine provided satisfactory protection against indomethacin-induced mucosal injury in mice, most probably via its role as a nitric oxide donor. So supplementation with dietary arginine is recommended