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

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

Study of both ghrelin hormone and serum TNF-alpha in patients with inflammatory bowel disease; their relation to degree of disease activity

Crohn's disease and ulcerative colitis, both defined as inflammatory bowel diseases [IBD], are idiopathic inflammatory disorders of gut mucosa of unknown etiology. The clinical course of both diseases can differ from a mild form to a severe form. TNF- alpha is a key pro-inflammatory cytokine in IBD and in other chronic inflammatory conditions. A substantial amount of research has been conducted concerning TNF- alpha and anti-TNF- alpha therapies. Ghrelin, a hormone secreted from the stomach with orexigenic, adipogenic, and somatotropic properties, functions through the stimulation of its receptor, the growth hormone secretagogue receptor [GHS-R], leading to release of growth hormone. Although GHS-R and ghrelin are expressed in human T lymphocytes and monocytes, yet its role in regulation of immune responses remains undefined. was to study both ghrelin hormone and serum TNF-alpha in inflammatory bowel disease and their relation to degree of activity. The study included twenty patients with inflammatory bowel disease in varying degrees of activity and ten healthy volunteers were taken as control. All patients had undergone thorough clinical examination, calculation of body mass index, Ileocolonoscopy and biopsy, calculation of degree of disease activity, and measurement of serum Ghrelin hormone and serum TNF- alpha. The mean serum Ghrelin in IBD patients was significantly higher than in control group [802.4 +/- 51.14 versus 227.25 +/- 39.45 pg/ml respectively p=0.000]. Moreover, the mean serum ghrelin level in patients with moderate to severe activity was significantly higher than inatients with mild activity [828.89 +/- 32.48 versus778.91 +/- 55.11 pg/ml respectively] [p=0.012]. Also, Ghrelin hormone correlates positively with C-reactive protein. The mean serum TNF-alpha level was significantly higher in patients than in control group [60.20 +/- 59.86 versus 22.2 +/- 15.70 ng /ml respectively p=0.007]. The mean TNF- alpha level for patients with mild activity was 53.36 +/- 52.27 and was 68.56 +/- 70.37 for patients with moderate to severe activity, with no statistically significant difference between the two groups [p=0.299]. Serum ghrelin hormone increases significantly in IBD than in control group and correlates positively with the degree of IBD activity, while serum TNF-alpha,although significantly increased in patients with IBD yet it doesn't correlate statistically with disease activity