Effects of esomeprazole on glutathione levels and mitochondrial oxidative phosphorylation in the gastric mucosa of rats treated with indomethacin

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 lesio...

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Bibliographic Details
Published in:	Naunyn-Schmiedeberg's archives of pharmacology Vol. 378; no. 4; pp. 421 - 429
Main Authors:	Pastoris, O., Verri, M., Boschi, F., Kastsiuchenka, O., Balestra, B., Pace, F., Tonini, M., Natale, G.
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Springer-Verlag 01-10-2008
Subjects:	Animals Anti-Inflammatory Agents, Non-Steroidal - administration & dosage Anti-Inflammatory Agents, Non-Steroidal - toxicity Anti-Ulcer Agents - administration & dosage Anti-Ulcer Agents - pharmacology Biomedical and Life Sciences Biomedicine Dose-Response Relationship, Drug Electron Transport Complex I - metabolism Electron Transport Complex II - metabolism Esomeprazole - administration & dosage Esomeprazole - pharmacology Gastric Mucosa - drug effects Gastric Mucosa - metabolism Gastric Mucosa - pathology Glutathione - metabolism Glutathione Disulfide - metabolism Indomethacin - administration & dosage Indomethacin - toxicity Intubation, Gastrointestinal Male Membrane Transport Proteins - metabolism Mitochondria - drug effects Mitochondria - metabolism Necrosis Neurosciences Original Article Oxidative Phosphorylation - drug effects Pharmacology/Toxicology Rats Rats, Wistar Spectrophotometry - methods Stomach Diseases - chemically induced Stomach Diseases - metabolism Stomach Diseases - pathology Nonsteroidal anti-inflammatory drugs (NSAIDs) Esomeprazole Gastric mucosa Oxidative injury
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Summary:	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 µmol/kg; indomethacin 100 µmol/kg; and esomeprazole 10, 30, or 60 µmol/kg plus indomethacin 100 µmol/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 µmol/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.
ISSN:	0028-1298 1432-1912
DOI:	10.1007/s00210-008-0314-7