Effect of 16.16 dimethyl prostaglandin E2, N-acetyl-cysteine and the proton pump inhibitor BY 831-78 on hydrogen peroxide-induced mucosal damage in the rat stomach.
Reactive oxygen species are noxious to gastrointestinal mucosa and contribute to a variety of gastrointestinal diseases. We examined whether 16.16 dimethyl prostaglandin E2 (PG) is protective against the oxidizing action of 6% H2O2 causing gross hemorrhagic lesions in rat gastric mucosa. Male Wistar rats were treated with PG, 0.005-5 micrograms/kg, either intragastrically (i.g.) or subcutaneously, 30 min prior to i.g. administration of 6% H2O2, 0.5 ml/100 g. Further animals received 25 mg of the mucus dissolvent N-acetyl-cystein (NAC) following oral PG treatment or 30 mumol/kg of the H+K(+)-ATPase inhibitor BY 831-78 (BY), 4 h before onset of the experiments. Volume, pH and beta-N-acetyl-glucosaminidase and lactate dehydrogenase as parameters of cell damage were determined in the gastric juice. i.g. PG treatment achieved 60 and 55% reduction of the mucosal lesions in doses between 5 and 0.05 micrograms/kg, respectively. i.p. PG administration was effective in all doses tested. Gastric juice volume was only slightly and enzymes were not significantly affected by PG treatment. NAC did not diminish PG efficacy or aggravate mucosal lesions. Gastric acid suppression did not increase PG-induced protection but was strongly protective by itself, reducing damage by 75%. Low-dose PG treatment achieves an effective protection against oxidative damage in gastric mucosa, which is not the result of dilution or enhanced mucus production.
Schürer-Maly
C C
CC
Gastrointestinal Unit, University Hospital, Inselspital Bern, Switzerland.
Haussner
V
V
Halter
F
F
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000111:Acetylcysteine / Q000494:pharmacology*; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles; D005750:Gastric Juice / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects*; D005756:Gastritis / Q000139:chemically induced / Q000517:prevention & control*; D006861:Hydrogen Peroxide; D008297:Male; D009093:Mucus / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D001562:Benzimidazoles; C061000:BY 831-78; D006861:Hydrogen Peroxide; D000251:Adenosine Triphosphatases; D015064:16,16-Dimethylprostaglandin E2; D000111:Acetylcysteine