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

• 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
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-008-0314-7

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.