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Antioxidant protection against oxidant-induced damage in cultured gastric mucosal cells

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Summary

Gastric epithelium is exposed not only to oxidants generated within the lumen, but also to those produced by ischemia/reperfusion. This study examined the mechanism(s) of oxidant-induced injury to cultured rat gastric mucosal cells, and characterized the antioxidant profile of these cells. Hydrogen peroxide (H2O2), generated by glucose oxidase, damaged cells dose-dependently, as assessed by increased leakage of labeled51Cr. Glucose oxidase-induced damage was prevented by exogenous catalase (but not by exogenous Superoxide dismutase). Chelation of cellular iron with desferrioxamine or phenanthroline specifically protected cells against H2O2, whereas binding of extracellular iron with apotransferrin failed to. Disruption of the glutathione redox cycle at three independent sites rendered cells less resistant to H2O2, whereas inhibition of cellular catalase did not result in sensitization of cells to H2O2. In conclusion, (1) oxidant injury induced by extracellular H2O2 is mediated by intracellular iron; (2) extracellular Superoxide is not involved in the damaging process; and (3) the glutathione redox cycle plays a principal role in detoxifying H2O2 as a cellular antioxidant in cultured gastric mucosal cells.

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Abbreviations

BCNU:

l,3-bis(chloroethyl)-l-nitrosourea

BSO:

buthionine sulfoximine

DEM:

diethyl maleate

GSH:

reduced glutathione

GSSG:

oxidized glutathione

H2O2 :

hydrogen peroxide

OH:

hydroxyl radical

O2 :

Superoxide anion

SOD:

Superoxide dismutase

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Correspondence to Hideyuki Hiraishi.

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Hiraishi, H., Yajima, N., Yamaguchi, N. et al. Antioxidant protection against oxidant-induced damage in cultured gastric mucosal cells. Gastroenterol Jpn 28, 132 (1993). https://doi.org/10.1007/BF02989224

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Keywords

  • H202
  • Glucose Oxidase
  • BCNU
  • Desferrioxamine
  • 51Cr Release