Objective: Helicobacter pylori is the main cause of gastritis, gastroduodenal ulcerand gastric cancer and should be considered as a major public health issue.According to several international guidelines first line therapy for treatingHelicobacter pylori infection consists of the usage of macrolide antibiotic(clarithromycin) in combination with other anti secretory agents which has shown tobe related to eradication of the microorganism. Although clarithromycin, has beenused successfully with antiulcer agents to prolong duodenal ulcer remission it is notwell known if it possess cytoprotective effects as well. The aim of the present studywas to examine whether clarithromycin may have gastroprotective effect against 96%ethanol induced gastric lesion in rats and to elucidate the role played by opiatereceptors, afferent sensory nerve fibers, and -adrenoceptores, endogeneousprostaglandins, sulfhydryls, fluid volume and mucous volume retained in the gastriclumen, in the mechanism of protection offered by intragastric clarithromycin againstethanol-induced mucosal injury. Methods: Gastric mucosal lesions were induced by96% ethanol in rats, then the effect of intragastric clarithromycin (in a doserange:50-400 mg/kg b.wt.) on the ethanol-induced lesion was studied. The effect of blochageof opiate receptors was studied using opiate receptor blocking agent naloxone (8mg/kg.b.wt. intraperitoneal),denervation of the sensory afferent nerves was done byusage of capsaicin (125 mg/kg b. wt. Subcutaneous),the effect of adrenergicreceptor was done by using 1 adrenergic receptor antagonist prazosin (0.5 mg/kgb. wt. subcutaneous), while the effect of 2 adrenergic receptor was examined byusage of 2 adrenergic receptor antagonist yohimbine (5 mg/kg b. wt.subcutaneous), the influence of 1 adrenoceptores was tested by using 1adrenoceptores antagonist metoprolol (2 mg/kg b. wt. intraperitoneal), while theeffect of 2 adrenoceptores was done by using of 2 adrenoceptores blokerbutoxamine (4 mg/kg b. wt. intraperitoneal), the effect of endogenous prostaglandinswas assassed by application of cycloxygenase inhibitor indomethacin (5mg/kg b. wt.subcutaneous) and sulphhydryls blocking agent is used (iodoacetamide) in a dose of(100 mg/kg. b.wt. subcutaneous). In addition, the effect of clarithromycin on thevolume of gastric content was also investigated. Each study was carried out using sixrats per group. Results: It has been found that intragastric administration ofclarithromycin protected the rat gastric mucosa against 96% ethanol-induced lesionin a dose dependent manner. The inhibition of lesions was 31.86, 51.33, 79.65 and
91.15% at doses of 50, 100, 200 and 400 mg/kg b.wt. respectively. Thegastroprotective effect of clarithromycin was not significantly modified bypretreatment with either opiate receptor blocking agent; or sensory nerve fiberdenervation. Subcutaneous pretreatment of rats with 1 blocker or intraperitonealpretreatment with 1 or 2 blocker did not significantly modify the gastroprotectiveeffect of clarithromycin, however, clarithromycin protection was significantlydiminished, although not completely abolished by subcutaneous 2 blocking agent.Clarithromycin protection was not significantly modified by pretreatment with eithersubcutaneous cycloxygense inhibitor, or sulfhydrls blocker. In addition there was adose dependent increase in fluid volume for clarithromycin and in the mucous volumeat 100, 200 and 400 mg/kg b. wt. of clarithromycin at 30 min. 2 blocking agentsignificantly reduced both basal and clarithomycin-stimulated gastric mucoussecretion. Conclusion: It could be concluded that the mechanism mediating theintragastric clarithromycin protective effect against 96% ethanol induced mucosallesion is independent of opiate receptors, capsaicin-sensitive afferent sensory nervefibers, 1, - 1-,2-adrenoceptors, endogenous prostaglandins, and sulfhydrylcompounds of the gastric mucosa. However, the increase in luminal gastric mucousand fluid volume may contribute to the protective effect of intragastric clarithromycinagainst 96% ethanol-induced gastric lesion, 2-adrenoceptors possibly are involvedin such protection by a mucous dependent mechanism.