KETOTIFEN AND NITROXIDES DECREASE CAPSAICIN-AUGMENTED ETHANOL-INDUCEDGASTRIC DAMAGE IN RATS

Systemic administration of capsaicin aggravates ethanol-induced injury of rat gastric mucosa. We evaluated the effect of subcutaneous admini stration of capsaicin on the gastric mucosa and on inflammatory mediat ors in saline- and ethanol-treated rats. Functional ablation of primar y afferent C-fibers by capsaicin (total 100 mg/kg subcutaneous) triple d ethanol-induced damage. Pretreatment with ketotifen, a mast cell sta bilizer (1 mg/kg) protected rat gastric mucosa from the amplified inju ry induced by capsaicin and ethanol. Tempol, a selective nontoxic cell -permeable nitroxide, completely prevented the amplified gastric ulcer ation induced by capsaicin and ethanol. This was accompanied by a sign ificant decrease in leukotriene B-4 and C-4 generation. It is therefor e suggested that mast cells and free radicals contribute to the amplif ied injury observed in rats pretreated with capsaicin and ethanol and that the pharmacological modulation of mast cell release and scavengin g of free radicals may be of therapeutic efficacy in the prevention of gastric injury.