Effects of L-arginine and L-citrulline on Indomethacin-Induced Gastric Ulceration and Gastric pH in Male Albino Rats

Abstract

Aims: The anti-ulcerogenic activity of L-arginine and L-citrulline were evaluated in indomethacin-induced gastric ulceration. Degree of ulcerogenesis, gastric pH and microscopic histological evaluation were carried out. Study Design: Six groups of albino rats weighing between 180-280g were pre-treated respectively with distilled water (ulcer control), omeprazole (20mg/kg, reference control 1), cimetidine (100mg/kg reference control 2), L-arginine (experimental control 1), 300mg/kg and 900mg/kg L-citrulline (experimental controls 2 and 3). Place and Duration of Study: Department of Physiology, College of Medicine. University of Ibadan, Nigeria between April 2012 and February 2013. Methodology: Forty-eight albino rats weighing between 180-280g were pre-treated respectively with distilled water (ulcer control), omeprazole (20mg/kg, reference control 1), cimetidine (100mg/kg reference control 2), L-arginine (experimental control 1), 300mg/kg and 900mg/kg L-citrulline (experimental controls 2 and 3) sixty minutes prior to oral administration of indomethacin to generate gastric mucosal injury. ). Ulcer was induced using 40mg/kg BW Indomethacin. Four hours later, rats were sacrificed and gastric contents as well as stomach wall samples were collected. Gastric ulcer score was determined macroscopically as well as gastric pH. Tissue samples were also prepared and examined histologically Results: With gross examination, ulcer control exhibited severe injury to the gastric mucosa and decreased pH of gastric contents, whereas rats pre-treated with L-arginine and L-citrulline showed significant dose-dependent reduction of gastric lesion formation accompanied by significant increase in gastric mucus production and pH of gastric fluid. Gastric protection was more prominent in L-arginine (300mg/kg) and L-citrulline (900mg/kg) groups. Histologically, the ulcer control showed the most severe and deepest gastric mucosal necrotic damage, with oedema of the submucosal layer compared to experimental and reference control groups. Conclusion: The results suggest that a possible explanation for the protective activity of L-arginine and L-citrulline may be due its stimulation of defensive mucin secretion and a consequent increase in pH of gastric contents, which result in less mucosal injury and limited or absent oedema of submucosa.