Effects of two benzimidazoles as proton pump inhibitors on water immersion stress-induced gastric ulcers in rats.
This study was designed to clarify effects of proton pump inhibitors, E-3810(2-([4-(3-methoxypropoxy)-3methylpyridine-2-yl]methyl- sulfinyl)-1H-benzimidazol sodium salt) and omeprazole (CAS 73590-58-6), on water immersion stress-induced gastric ulcers in relation to mucosal prostaglandins (PGs) and leukotrienes (LTs). Mucosal PGs were measured by high performance liquid chromatography (HPLC). In untreated rats, 4 kinds of PGs, i.e., 6-keto-PGF1 alpha, PGF2 alpha, PGE2 and PGD2 were detected in gastric mucosa, but no LTs were detected. Water immersion stress for 6 h caused severe hemorrhagic lesions in the fundic portion and, concomitantly, significant decreases in mucosal PG levels. On the other hand, LTC4 and LTD4 were detected after 6 h stress treatment, though LTB4 and LTE4 were not detected throughout the experiments. Peptide-LT (the sum of LTC4 and LTD4) levels were 23.5 +/- 3.2 ng/g tissue 6 h after water immersion stress. Administration of 20 mg/kg of E-3810 or 20 mg/kg of omeprazole mitigated gastric lesions and increases in the mucosal peptide-LT levels, but dit not improve the decrease in mucosal PGs.
Goto
H
H
Department of Internal Medicine, Faculty of Medicine, University of Nagoya, Japan.
Sugiyama
S
S
Tsukamoto
Y
Y
Kuroiwa
M
M
Ohara
A
A
Hoshino
H
H
Nakazawa
S
S
Ozawa
T
T
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D007101:Immersion; D015289:Leukotrienes / Q000096:biosynthesis; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis; D011522:Protons; D064750:Rabeprazole; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000209:etiology / Q000517:prevention & control*; D013315:Stress, Psychological / Q000150:complications*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D015289:Leukotrienes; D011453:Prostaglandins; D011522:Protons; D064750:Rabeprazole; D000251:Adenosine Triphosphatases; D009853:Omeprazole