Document Detail


Reactive oxygen species are involved in the apoptosis induced by nonsteroidal anti-inflammatory drugs in cultured gastric cells.
MedLine Citation:
PMID:  10594327     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously reported the induction of apoptotic DNA fragmentation by nonsteroidal anti-inflammatory drugs (NSAIDs) in cultured rat gastric cells, and indicated that prostaglandin-synthesis is only marginally involved in the apoptotic process. In the present study, we examined whether the generation of reactive oxygen species is critically involved in NSAID-induced apoptosis. Indomethacin, sodium diclofenac, flurbiprofen, zaltoprofen, etodolac, but not mofezolac, enhanced apoptotic DNA fragmentation and mRNA expression for cyclooxygenase-2 in AGS cells, a cell line derived from human gastric epithelium. The apoptotic effect of indomethacin was then confirmed by fluorescent staining of the cells with annexin V. Apoptotic DNA fragmentation induced by indomethacin and flurbiprofen was suppressed by incubation of the cells with the anti-oxidants pyrrolidine dithiocarbamate, diphenyleneiodonium chloride, and N-acetyl-L-cysteine. These two NSAIDs also enhanced release from the cells of 8-isoprostane, a nonenzymatic product by free-radical-mediated peroxidation of arachidonic acid. Further, lucigenin chemiluminescence showed that the intracellular production of reactive oxygen species increased in cells treated with indomethacin. The present data thus indicate a crucial association between the generation of reactive oxygen species and NSAID-induced apoptosis in gastric epithelial cells.
Authors:
H Kusuhara; H Komatsu; H Sumichika; K Sugahara
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European journal of pharmacology     Volume:  383     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1999 Nov 
Date Detail:
Created Date:  2000-01-27     Completed Date:  2000-01-27     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  331-7     Citation Subset:  IM    
Affiliation:
Research Laboratories, Yoshitomi Pharmaceutical Industries, Shodai-Ohtani 2-25-1, Hirakata, Japan. kusuhara@yoshitomi.co.jp
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MeSH Terms
Descriptor/Qualifier:
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Antioxidants / pharmacology
Apoptosis / genetics*
Cells, Cultured
Cyclooxygenase Inhibitors / pharmacology
DNA Fragmentation
Epithelial Cells / drug effects*,  physiology
Humans
Indomethacin / pharmacology
Prostaglandin-Endoperoxide Synthases / drug effects,  metabolism
RNA, Messenger / drug effects,  metabolism
Reactive Oxygen Species / physiology*
Stomach / cytology*
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Antioxidants; 0/Cyclooxygenase Inhibitors; 0/RNA, Messenger; 0/Reactive Oxygen Species; 53-86-1/Indomethacin; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases

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