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Effects of esomeprazole on glutathione levels and mitochondrial oxidative phosphorylation in the gastric mucosa of rats treated with indomethacin.
- Source :
-
Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2008 Oct; Vol. 378 (4), pp. 421-9. Date of Electronic Publication: 2008 Jun 11. - Publication Year :
- 2008
-
Abstract
- Proton pump inhibitors exert their preventive and healing effects on gastropathy induced by nonsteroidal anti-inflammatory drug (NSAIDs) by a dual action: the antisecretory and the antioxidant effect. The latter was investigated by using esomeprazole against indomethacin-induced gastric mucosa lesions in rats and assessed by a histomorphometric analysis. Treatment by intragastric gavage were 1% methocel as vehicle; esomeprazole 10, 30, or 60 micromol/kg; indomethacin 100 micromol/kg; and esomeprazole 10, 30, or 60 micromol/kg plus indomethacin 100 micromol/kg. The evaluation of glutathione (GSH) levels and respiratory chain complex activities [nicotinamide adenine dinucleotide, reduced (NADH)-ubiquinone oxidoreductase, succinate dehydrogenase, cytochrome C reductase, cytochrome oxidase] was performed in the isolated gastric mucosa. Esomeprazole (10-60 micromol/kg) dose dependently reversed, up to complete recovery, the inhibitory effect of indomethacin on GSH levels (approximately 60% inhibition) and mitochondrial enzyme activities (inhibition ranging from 60% to 75%). Indomethacin-induced mucosal injuries were reduced by esomeprazole. Thus, in addition to inhibiting acid secretion, the gastroprotective effect of esomeprazole can be ascribed to a reduction in gastric oxidative injury.
- Subjects :
- Animals
Anti-Inflammatory Agents, Non-Steroidal administration & dosage
Anti-Inflammatory Agents, Non-Steroidal toxicity
Anti-Ulcer Agents administration & dosage
Anti-Ulcer Agents pharmacology
Dose-Response Relationship, Drug
Electron Transport Complex I metabolism
Electron Transport Complex II metabolism
Esomeprazole administration & dosage
Gastric Mucosa metabolism
Gastric Mucosa pathology
Glutathione Disulfide metabolism
Indomethacin administration & dosage
Intubation, Gastrointestinal
Male
Membrane Transport Proteins metabolism
Mitochondria metabolism
Necrosis
Oxidative Phosphorylation drug effects
Rats
Rats, Wistar
Spectrophotometry methods
Stomach Diseases chemically induced
Stomach Diseases metabolism
Stomach Diseases pathology
Esomeprazole pharmacology
Gastric Mucosa drug effects
Glutathione metabolism
Indomethacin toxicity
Mitochondria drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0028-1298
- Volume :
- 378
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Naunyn-Schmiedeberg's archives of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 18545984
- Full Text :
- https://doi.org/10.1007/s00210-008-0314-7