Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

The aim of this work is to investigate the potential gastroprotective effect of a specific phosphodiesterase 3 inhibitor namely cilostazole (5 or 10 mg/kg, p.o.) and plant product namely G. sylvestre (200 or 400 mg/kg, p.o.) either singly or in combination in comparison with the standard antiulcer ranitidine (50 mg/kg, p.o.) on peptic ulcer induced by either ethanol or pyloric ligation in male adult albino rats. Gastric mucosa was examined macroscopically, histologically, and biochemically for ulcer severity, markers of oxidative stress, proinflammatory cytokines, apoptotic, and cytoprotective mediators. Gastric acidic output, peptic activity, and mucin content were measured in gastric fluids. Pretreatment with cilostazol or G. sylvestre reduced ulcer number and severity, ameliorated redox status (reduced glutathione and malonaldehyde content), and decreased levels of IL-1Ý, IL-6, and TNF- in gastric mucosa, in parallel with increases in mucosal defensive factors nitric oxide (NO), prostaglandin E2 (PGE2), and heat-shock protein 70 (HSP70) promoting mucus secretion, tissue perfusion, and regeneration. In addition, G. sylvestre reduced gastric acid secretion while no such changes were observed by cilostazol. The gastroprotective effect of cilostazol may be related to an increase of the cAMP content in mucous cells via inhibition of PDE 3, while G. sylvestre effects may be attributed to its constituent as triterpenes, flavonoids, glycosides and anthroquinones. The results showed also that the combined use of cilostazol and G

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