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Omeprazole abrogates cell protection in an in vitro model of infectious gastritis
Author(s) -
Blass Amy L.,
Kohler Jonathan E.,
Liu Jingjing,
Mathew Jeff,
Tai Kaniza,
Kelly Edward,
Soybe David I.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1182.6
Subject(s) - thiol , chemistry , chelation , omeprazole , programmed cell death , viability assay , intracellular , antidote , in vitro , dithiothreitol , reducing agent , pharmacology , microbiology and biotechnology , biochemistry , apoptosis , enzyme , medicine , biology , toxicity , inorganic chemistry , organic chemistry
Aim: Monochloramine (NH 2 Cl) is a thiol oxidant produced in H. pylori gastritis. Omeprazole (OME) is a proton pump inhibitor, and a thiol oxidant, used to treat gastritis. Our aim was to determine if OME influences cell injury by NH 2 Cl, and to test if effects of these thiol oxidants are mediated by changes in [Ca 2+ ] i and [Zn 2+ ] i . Methods: Isolated rabbit gastric glands were incubated with doses of NH 2 Cl for 3 hours, and cell viability was measured with Calcein‐AM. Chelators (BAPTA or TPEN) and a thiol reducing agent (DTT) were added, with or without OME. Results were normalized to Ringers controls. Results: NH 2 Cl caused cell death at all concentrations. DTT protected cells from NH 2 Cl‐induced damage. The promiscuous chelator BAPTA gave no protection. However, the zinc‐specific chelator TPEN protected completely. When cells were co‐incubated with OME, cell death occurred even in the absence of NH 2 Cl. Addition of TPEN to these cells was not protective despite high [Zn 2+ ] i , but addition of DTT again prevented cell death. Conclusion: Chelation of intracellular Zn 2+ , but not Ca 2+ , protects cells exposed to NH 2 Cl. However, OME, commonly used to treat H. pylori gastritis, appears to cause zinc‐independent cell death. This can be reversed by the thiol‐reducing agent DTT, suggesting that OME acts downstream of Zn 2+ ‐mediated injury. Funding: NIH R01DK069929‐03