EVALUATION OF GASTROPROTECTIVE EFFICACY AND SAFETY PROFILE OF LOW DOSE CIMETIDINE AND L-GLUTAMINE USING GASTRIC AND DUODENAL ULCER MODELS IN RATS
OKPO SO, AKINRINDE AO, OTTIH AE, ANAZODO U, CHIJIOKE MC
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Benin City 300001, Nigeria
- Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, NIGERIA
Afr. J Pharm Res Dev; Volume 8(1): 42-53; June/July 2016
ABSTRACT
The long-term use of histamine H2-receptor blockers especially cimetidine and ranitidine at recommended doses in peptic ulcer disease is associated with various adverse effects. The dose-dependent nature of these adverse effects calls for the use of low doses of these drugs in combination with an amino acid supplement with cytoprotective activity to reduce the adverse effects, improve compliance and achieve positive outcomes. The present study evaluates the gastroprotective efficacy of a combination of low dose cimetidine with L-glutamine on acutely induced gastric and duodenal lesions using ethanol/hydrochloric acid, water immersion and cysteamine, and chronically induced gastric ulcers using ethanol and indomethacin/pyloric ligation. The effects of long term administration of the drug combination on sperm count/motility and testosterone level were also evaluated. Acute gastric ulcers were induced by intragastric instillation of 0.15 M Hydrochloric acid in 70 % v/v ethanol and water immersion stress in rats while duodenal ulcer was induced using cysteamine. Chronic gastric ulcers, on the other hand, were generated by administration of ethanol (70 % maintained with 20 % ethanol for 6 days) and indomethacin (20 mg/kg) + pyloric ligation. Animals were administered the drugs orally for 21 days (in chronic ethanol-induced) and 7 days (for indomethacin/pyloric ligation). Parameters measured included ulcer indices (severity and score), superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA), sperm count, sperm motility, testosterone levels. Oral administration of a combination of L-glutamine (200 mg/kg) and cimetidine (10 mg/kg) caused significant (p<0.01) reductions in the number and severity of ulcerations in all the models of ulcer used, compared to the control. However, no significant changes were observed in sperm count and motility as well as blood testosterone level compared to when cimetidine was used alone. The study showed that a combination of low dose cimetidine with L-glutamine conferred protective effects on acute gastric and duodenal injuries as well as chronic gastric injury produced by ethanol and indomethacin/pyloric ligation in rats. There was, however, no apparent attenuation of the side effects associated with cimetidine based on the parameters measured.
*Corresponding Author: steveokpo@uniben.edu