Reactive oxygen species are involved in the apoptosis induced by nonsteroidal anti-inflammatory drugs in cultured gastric cells.

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Kusuhara H, Komatsu H, Sumichika H, Sugahara K

Reactive oxygen species are involved in the apoptosis induced by nonsteroidal anti-inflammatory drugs in cultured gastric cells.

Eur J Pharmacol. 1999 Nov 3;383(3):331-7.

PubMed ID

10594327 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Etodolac	Prostaglandin G/H synthase 2	Protein	Humans	Yes	Inhibitor	Details

Pharmaco-transcriptomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Diclofenac	Approved Vet Approved	PTGS2	5743	upregulated	Diclofenac results in increased expression of PTGS2 mRNA	1q31.1
Etodolac	Approved Investigational Vet Approved	PTGS2	5743	upregulated	Etodolac results in increased expression of PTGS2 mRNA	1q31.1
Flurbiprofen	Approved Investigational	PTGS2	5743	upregulated	Flurbiprofen results in increased expression of PTGS2 mRNA	1q31.1
Indomethacin	Approved Investigational	PTGS2	5743	upregulated	Indomethacin results in increased expression of PTGS2 mRNA	1q31.1