The role of nitric oxide on cigarette smoke-induced programmed cell death in the gastric mucosa.
BACKGROUND
This study was designed to investigate the effect of cigarette smoking on apoptosis in the gastric mucosa and the role of nitric oxide (NO) in the gas phase and extracts in the tar phase in this pathological process.


METHODS
Male Sprague-Dawley rats and human gastric epithelial cell line AGS were used in the study.


RESULTS
Cigarette smoking significantly increased apoptotic bodies in the rat gastric mucosa. However, neither filtered cigarette smoke, in which most of the substances in the tar phase were removed, nor oral administration of the two cigarette smoke extracts produced any effect on apoptosis. Interestingly, in this experiment pretreatment with a NO donor, the chloroform extract (CE) could significantly increase apoptosis. In in vitro study, only the CE induced DNA fragmentation, which could be elevated further by preincubation with a NO donor. The same extract also elevated inducible nitric oxide synthase (iNOS) activity. Inhibition of iNOS by N(G)-nitro-L-arginine methylester hydrochloride (L-NAME) partially abolished CE-induced apoptosis.


CONCLUSIONS
These findings suggested that exogenous and endogenous NO had a synergistic effect with substances in the tar phase to induce programmed cell death in gastric epithelial cells both in vivo and in vitro.
Wang
H Y
HY
Dept. of Pharmacology, Faculty of Medicine, The University of Hong Kong, HKSAR, China.
Ma
L
L
Li
Y
Y
Cho
C H
CH
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D002725:Chloroform / Q000494:pharmacology; D004195:Disease Models, Animal; D004847:Epithelial Cells; D005753:Gastric Mucosa / Q000166:cytology / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity; D012907:Smoking / Q000009:adverse effects*
D009599:Nitroprusside; D009569:Nitric Oxide; D002725:Chloroform; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester