Effect of cigarette smoke on ethanol-induced gastric mucosal lesions: the role of nitric oxide and neutrophils.
The roles of neutrophil aggregation, inducible nitric oxide synthase activation and chemoattractant, leukotriene B4, in potentiation of the cigarette smoke effect on ethanol-induced gastric mucosal damage were studied. Smoke exposure markedly increased gastric lesion formation following ethanol administration and this was accompanied by substantial increase in gastric mucosal leukotriene B4 concentration, myeloperoxidase and inducible nitric oxide synthase activities. Antineutrophil serum or aminoguanidine pretreatment significantly attenuated both gastric mucosal lesion formation and inducible nitric oxide synthase activity. The increased myeloperoxidase activity was abolished by antineutrophil serum but not by aminoguanidine. These data indicated that both neutrophil mobilization and inducible nitric oxide synthase activation in the gastric mucosa play an important role in the potentiating action of cigarette smoke on ethanol-induced gastric mucosal lesion formation. Increased synthesis of nitric oxide from inducible nitric oxide synthase during gastric damage may be secondary to neutrophil infiltration in the gastric mucosa. Chemoattractant leukotriene B4 could also contribute to neutrophil recruitment in the tissue.
Chow
J Y
JY
Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, PR China.
Ma
L
L
Cho
C H
CH
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002449:Cell Aggregation / Q000502:physiology; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000633:toxicity*; D005753:Gastric Mucosa / Q000201:enzymology / Q000473:pathology; D007975:Leukotriene B4 / Q000502:physiology; D008297:Male; D009503:Neutropenia / Q000503:physiopathology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000473:pathology*; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology*
D000906:Antibodies; D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D007975:Leukotriene B4; D009569:Nitric Oxide; D000431:Ethanol; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat