The cytoprotective action of metronidazole in rats stomachs

Abstract

We demonstrated that amoxiciUin imparted gastric cytoprotection when ~dministered before the fat stomachs were challenged by ethanol (J. Gastroenterol. Hepatol. 1994, 9:514-8). This study was performed to evaluate if metronidazole has a similar protective property. Sprague-Dawiey rats (230-250 g) were used for these experiments. These animals were fasted for 24 hrs before metronidazole (5 or 10 mg/kg) or its vehicle (controls) administered via the oral or intraperitoneal route before ethanol (40%, v/v 10 ml/kg) or ~domethaein (30 mg/kg) ingestion. The severity ofmucosal lesions was assessed by measuring the lesion areas and the intramucosal mucus thickness was determined by the histochemical method. An ex-vivo gastric chamber was used to measure the changes in basal mucosal blood flow (the laser-Doppler method) with the same doses of metronidazole. Finally, the direct cytoprotective effect of the drug was assessed by the viability and lactate dehydrogenase release from an o isolated gland preparation after ethanol (10'A, v/v) incubation. Metronidazole pretreatment by either route markedly prevented ethanol-induced gastric mucosal injury by 4-5 folds. Similar protection was observed in the indomethacin-treated animals, indicating that the antiulcer action was unlikely to be prostaglandin-mediated. The drug did not affect the gastric intramucosal mucus thickness or the basal mucosal blood flow. Metronidazole preincubation (10 "~ or 10 .4 M) significantly attenuated the damaging effect of ethanol on the viability of isolated glands (from 80% to 92%), and there was also a parallel significant reduction (3 folds) in lactate dehydrogenase release from the gland preparation. It is concluded that metronidazole prevents ethanol-induced mucosal lesions by a direct cytoprotective action on the gastric glandular mucosa.