Ketotifen and nitroxides decrease capsaicin-augmented ethanol-induced gastric damage in rats.
Systemic administration of capsaicin aggravates ethanol-induced injury of rat gastric mucosa. We evaluated the effect of subcutaneous administration of capsaicin on the gastric mucosa and on inflammatory mediators in saline- and ethanol-treated rats. Functional ablation of primary afferent C-fibers by capsaicin (total 100 mg/kg subcutaneous) tripled ethanol-induced damage. Pretreatment with ketotifen, a mast cell stabilizer (1 mg/kg) protected rat gastric mucosa from the amplified injury induced by capsaicin and ethanol. Tempol, a selective nontoxic cell-permeable nitroxide, completely prevented the amplified gastric ulceration induced by capsaicin and ethanol. This was accompanied by a significant decrease in leukotriene B4 and C4 generation. It is therefore suggested that mast cells and free radicals contribute to the amplified injury observed in rats pretreated with capsaicin and ethanol and that the pharmacological modulation of mast cell release and scavenging of free radicals may be of therapeutic efficacy in the prevention of gastric injury.
Karmeli
F
F
Department of Medicine, Hadassah University Hospital-Mount Scopus, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Eliakim
R
R
Okon
E
E
Rachmilewitz
D
D
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D002211:Capsaicin / Q000009:adverse effects*; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D000431:Ethanol / Q000009:adverse effects*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals; D005753:Gastric Mucosa / Q000187:drug effects* / Q000294:innervation; D007665:Ketotifen / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000378:metabolism; D017997:Leukotriene C4 / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects; D010972:Platelet Activating Factor / Q000378:metabolism; D011292:Premedication; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D005609:Free Radicals; D010972:Platelet Activating Factor; D011500:Protein Synthesis Inhibitors; D013113:Spin Labels; D007975:Leukotriene B4; D017997:Leukotriene C4; D000431:Ethanol; D015121:6-Ketoprostaglandin F1 alpha; D002211:Capsaicin; C001803:tempol; D007665:Ketotifen