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PEPTIC ULCER: PATHOGENESIS, HEALING AND ANTI‐ULCER DRUGS
Author(s) -
GYÖMBER E.,
VATTAY P.,
SZABO S.,
RAINSFORD KD
Publication year - 1996
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.1996.tb00274.x
Subject(s) - medicine , aspirin , pharmacology , pathogenesis , antagonist , oral administration , gastroenterology , iodoacetamide , leukotriene , cyclooxygenase , enzyme inhibitor , asthma , receptor , enzyme , biochemistry , chemistry , cysteine
Studies were performed in three models of acute gastric mucosal damage (induced by oral ethanol, aspirin and indomethacin) and a model of chronic gastritis (induced by 7 day treatment with iodoacetamide) in rats to establish the role of leukotrienes (LTs) in the pathogenesis of these lesions. The protective effects of highly selective 5‐lipoxygenase (5‐LO) inhibitors and leukotriene antagonists were thus examined in rats given these ulcerogens. Ethanol (1 mL, p.o.)‐induced haemorrhagic lesions were significantly reduced by prior oral administration of the 5‐LO inhibitor L‐656 224 (50 mg/kg), whereas lower doses of this drug were ineffective. Prior treatment with oral doses (5 and 10 mg/kg) of the 5‐LO inhibitor L‐655 224 or the LT antagonists L‐649 923 or L‐660 711, failed to affect lesions induced by aspirin (100 mg/kg, p.o.) and indomethacin (400 mg/kg, s.c), whereas higher doses of all three drugs (50 mg/kg) showed protective effects. Repeated prior dosing up to 5 h with the novel five lipoxygenase activating protein (FLAP) inhibitor, MK886 (50 and 100 mg/kg), reduced the lesions developed by indomethacin (30 mg/kg, s.c). Twice daily dosing with the 5‐LO inhibitor L‐656 224 (5 mg/kg) or the LT antagonist L‐649 923 (2 or 5 mg/kg) for 7 days significantly reduced the development of iodoacetamide‐induced gastritis during the period of induction of this condition, but higher doses of these inhibitors were not protective. We conclude that 5‐LO products partially mediate the production of gastric mucosal lesions induced by damaging agents, which varies according to the ulcer model employed; the limited protective effects of the respective 5‐LO inhibitors and LT antagonists depend on their individual pharmacokinetics and their time of dosing.