THE VASCULAR AND GLANDULAR ORGANOPROTECTIVE PROPERTIES OF METRONIDAZOLE IN THE RODENT STOMACH

Background: The gastroprotective action of metronidazole, an antimicro bial used in the therapy against Helicobacter pylori infection, is unc lear. Thus, the aim of the present investigation was to study the orga noprotective action and antiulcer mechanisms of this drug in rodents. Methods and results: Metronidazole (10 mg/kg), given either per os or intraperitoneally, 30 min beforehand, reduced ethanol (40%, 10 mL/kg, p.o.)-induced gastric mucosal damage in male rats. Likewise, oral admi nistration of metronidazole dose-dependently attenuated the indomethac in (30 mg/kg, p.o.)-induced gastric lesion formation and the concurren t depletion of mucosal mucus, However, metronidazole did not affect th e basal mucosal prostaglandin E-2 content. In an ex vivo gastric chamb er preparation, 40% ethanol incubation markedly lowered transmucosal p otential difference and increased mucosal vascular permeability in rat stomachs. Incubation with all doses of metronidazole did not modulate gastric mucosal blood flow nor transmucosal potential difference, eit her before or after ethanol treatment. Nevertheless, the increase in v ascular permeability by 40% ethanol was significantly alleviated by ei ther p.o. or i.p. metronidazole pretreatment, In addition, exposure of the isolated rabbit gastric gland preparation to metronidazole (10(-5 ) and 10(-4) M) significantly attenuated the damaging action of 10% et hanol. Conclusion: It is concluded that metronidazole possesses a dire ct Vascular and glandular organoprotective property in the rodent stom ach. However, the anti-ulcer action does not appear to involve prostag landins nor act through the improvement of gastric mucosal blood flow. Preservation of intramucosal mucus may partly contribute to the preve ntion of indomethacin-induced ulceration in rats.