The vascular and glandular organoprotective properties of metronidazole in the rodent stomach.
BACKGROUND
The gastroprotective action of metronidazole, an antimicrobial used in the therapy against Helicobacter pylori infection, is unclear. Thus, the aim of the present investigation was to study the organoprotective action and antiulcer mechanisms of this drug in rodents.


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 administration of metronidazole dose-dependently attenuated the indomethacin (30 mg/kg, p.o.)-induced gastric lesion formation and the concurrent depletion of mucosal mucus. However, metronidazole did not affect the basal mucosal prostaglandin E2 content. In an ex vivo gastric chamber preparation, 40% ethanol incubation markedly lowered transmucosal potential 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, either before or after ethanol treatment. Nevertheless, the increase in vascular permeability by 40% ethanol was significantly alleviated by either 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% ethanol.


CONCLUSIONS
It is concluded that metronidazole possesses a direct vascular and glandular organoprotective property in the rodent stomach. However, the anti-ulcer action does not appear to involve prostaglandins nor act through the improvement of gastric mucosal blood flow. Preservation of intramucosal mucus may partly contribute to the prevention of indomethacin-induced ulceration in rats.
Ko
J K
JK
Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Hong Kong.
Ching
C K
CK
Chow
J Y
JY
Zhang
S T
ST
Lam
S K
SK
Cho
C H
CH
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism*; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D007213:Indomethacin / Q000633:toxicity; D008297:Male; D008564:Membrane Potentials; D008795:Metronidazole / Q000627:therapeutic use*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D013272:Stomach Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D008795:Metronidazole; D000431:Ethanol; D015232:Dinoprostone; D007213:Indomethacin