Effects of omeprazole and ascorbate on gastric emptying and antioxidant levels in a mouse model of glutathione depletion

Koch, T.R.; Yuan, L.X.; Petro, A.; Opara, E.C.

Digestive Diseases and Sciences 47(11): 2486-2492


ISSN/ISBN: 0163-2116
PMID: 12452384
DOI: 10.1023/a:1020555925142
Accession: 003743704

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Increased free radical production with depletion of the antioxidant, glutathione, is a suggested mechanism for the development of ulcer disease in patients with Helicobacter pylori. The effects of ascorbate and omeprazole as potential gut antioxidants are incompletely understood. We hypothesized that as antioxidants, ascorbate and omeprazole protect against glutathione depletion. This study was designed to determine the effects of ascorbate and omeprazole on gastric emptying and gastric antioxidant levels in a mouse model of glutathione depletion. In an acute (10-day) mouse model, glutathione depletion was induced by inhibiting the rate limiting enzyme, gamma -glutamylcysteine synthetase. Enzymatic blockade produced depletion of gastric glutathione (P<0.05) without increasing gastric lipid hydroperoxides. Glutathione depletion was associated with accelerated liquid gastric emptying. These effects were not prevented by supplementation with ascorbate or omeprazole. Omeprazole induced increased (P<0.05) gastric and colonic total antioxidant capacity. One of the beneficial effects of omeprazole in patients may involve increased total antioxidant capacity.