Contributions of physical and chemical properties of mild irritants to gastric cytoprotection in rats

The present study demonstrated the cytoprotective abilities of low concentrations of ethanol, NaCl and HCl, against the gastric mucosal damage caused by 100% ethanol, and the contributions of the physical and chemical properties of these mild irritants to their protective actions. The results have shown the differential protective effects of ethanol (10-40%), NaCl (2.5-12.5%) and HCl (0.15-0.45M), with the optimal cytoprotective concentrations being 20% ethanol, 5% NaCl and 0.3M HCl, respectively. Solutions of KCl and NaCl with similar osmolarity, and H 2SO 4 and HCl of similar acidity and osmolarity, all showed similar protective potentials as compared to the osmotic agent mannitol, which possessed a concentration- and tonicity-dependent protective action against 100% ethanol-induced mucosal damage. Same concentration of methanol, propan-2-ol and ethanol, having similar osmolarity with deionized water, exerted indifferent protective effects. It is therefore concluded that adaptive cytoprotection induced by low concentrations of NaCl and HCl could depend on their physical properties, while that of ethanol could act through its unique chemical property.link_to_subscribed_fulltex

The cytoprotective action of metronidazole in rats stomachs

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.link_to_subscribed_fulltex