INVOLVEMENT OF FREE-RADICALS AND HISTAMINE IN THE POTENTIATING ACTIONOF CIGARETTE-SMOKE EXPOSURE ON ETHANOL-INDUCED GASTRIC-MUCOSAL DAMAGEIN RATS

Cigarette smoking has been associated with peptic ulcer diseases. We s tudied the effects of cigarette smoke exposure on ethanol-induced gast ric mucosal damage and its relationship with vascular integrity and th e possible role of free radicals and histamine. Male Sprague-Dawley ra ts were exposed to cigarette smoke followed by ethanol administration (70% v/v). Smoke exposure alone dose-dependently reduced basal blood f low and increased xanthine oxidase (XO) activity but superoxide dismut ase (SOD) activity remained unaffected in gastric mucosa. Cigarette sm oking followed by ethanol administration significantly potentiated muc osal lesion formation along with augmentation of the mucosal blood flo w, vascular permeability and myeloperoxidase (MPO) activity. The poten tiating effect of smoking on ethanol-induced gastric mucosal lesion an d MFO activity was abolished by pretreatment with allopurinol, terfena dine or ranitidine. Terfenadine and ranitidine also reduced the increa sed mucosal blood flow and vascular permeability induced by smoking an d ethanol combined. These findings suggested that cigarette smoke adve rsely affected the defense mechanisms of the gastric mucosa by reducin g the mucosal blood flow which in rum led to ischemia and increased XO activity. Activation of XO together with histamine H-1 and H-2 recept ors stimulation could lead to neutrophil aggregation and vascular dama ge. However, the potentiating action of cigarette smoke on ethanol ulc eration is unlikely through reduction of SOD activity in gastric mucos a. (C) 1998 Elsevier Science inc.