Cytoprotective effect of rabeprazole against ethanol-induced gastric mucosal damage: possible involvement of nitric oxide.
The cytoprotective effect of rabeprazole, a new proton pump inhibitor, against ethanol-induced gastric mucosal damage was investigated in rats. Rats received intraperitoneal injections of rabeprazole once only or once daily for 3 days. Subsequently, the rats were given 1 ml of absolute ethanol by oral intubation. Some rats given rabeprazole were treated with N-omega-nitro-L-arginine methyl ester (L-NAME) or indomethacin. Repeated administration of rabeprazole significantly inhibited ethanol-induced gastric mucosal damage, although single administration of this drug did not. Pretreatment with L-NAME abolished the cytoprotective effect of rabeprazole. This inhibitory effect of L-NAME was reversed by L-arginine but not by D-arginine. Pretreatment with indomethacin did not influence the cytoprotective effect of rabeprazole. These results suggest that repeated intraperitoneal administration of rabeprazole has a cytoprotective effect against ethanol-induced gastric mucosal damage and that this effect may be mediated via nitric oxide but not via prostaglandins.
Watanabe
T
T
Department of Biosignal Analysis, Osaka City University Medical School, Japan. watanabet@med.osaka-cu.ac.jp
Higuchi
K
K
Tominaga
K
K
Fujiwara
Y
Y
Arakawa
T
T
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000473:pathology*; D007213:Indomethacin / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009853:Omeprazole / Q000031:analogs & derivatives; D011453:Prostaglandins / Q000008:administration & dosage / Q000494:pharmacology; D064750:Rabeprazole; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D009569:Nitric Oxide; D064750:Rabeprazole; D019001:Nitric Oxide Synthase; D009853:Omeprazole; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin