Involvement of free radicals and histamine in the potentiating action of cigarette smoke exposure on ethanol-induced gastric mucosal damage in rats.
Cigarette smoking has been associated with peptic ulcer diseases. We studied the effects of cigarette smoke exposure on ethanol-induced gastric mucosal damage and its relationship with vascular integrity and the possible role of free radicals and histamine. Male Sprague-Dawley rats were exposed to cigarette smoke followed by ethanol administration (70% v/v). Smoke exposure alone dose-dependently reduced basal blood flow and increased xanthine oxidase (XO) activity but superoxide dismutase (SOD) activity remained unaffected in gastric mucosa. Cigarette smoking followed by ethanol administration significantly potentiated mucosal lesion formation along with augmentation of the mucosal blood flow, vascular permeability and myeloperoxidase (MPO) activity. The potentiating effect of smoking on ethanol-induced gastric mucosal lesion and MPO activity was abolished by pretreatment with allopurinol, terfenadine or ranitidine. Terfenadine and ranitidine also reduced the increased mucosal blood flow and vascular permeability induced by smoking and ethanol combined. These findings suggested that cigarette smoke adversely affected the defense mechanisms of the gastric mucosa by reducing the mucosal blood flow which in turn led to ischemia and increased XO activity. Activation of XO together with histamine H1 and H2 receptors stimulation could lead to neutrophil aggregation and vascular damage. However, the potentiating action of cigarette smoke on ethanol ulceration is unlikely through reduction of SOD activity in gastric mucosa.
Chow
J Y
JY
Department of Pharmacology, Faculty of Medicine, University of Hong Kong, China.
Ma
L
L
Cho
C H
CH
D000818:Animals; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D005609:Free Radicals / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D008297:Male; D010437:Peptic Ulcer / Q000209:etiology; D009195:Peroxidase / Q000378:metabolism; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000009:adverse effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D016593:Terfenadine / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism
D005609:Free Radicals; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D000431:Ethanol; D016593:Terfenadine; D006632:Histamine; D011899:Ranitidine; D009195:Peroxidase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase