Protective role of intracellular glutathione against ethanol-induced damage in cultured rat gastric mucosal cells

Journal Article · Fri Jun 01 04:00:00 EDT 1990 · Gastroenterology; (USA)

OSTI ID:6721204

Mutoh, H; Hiraishi, H; Ota, S; Yoshida, H; Ivey, K J; Terano, A; Sugimoto, T ^[1]

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1. Univ. of Tokyo (Japan)

This study investigated whether intracellular glutathione is cytoprotective against ethanol-induced injury to cultured rat gastric mucosal cells in vitro. Secondly, it investigated whether reduced glutathione or oxidized glutathione is responsible for this cytoprotection. Cytolysis was quantified by measuring 51Cr release from prelabeled cells. Concentrations of ethanol greater than 12% caused cell damage and increased 51Cr release in a dose-dependent and time-related fashion. When a substrate for glutathione synthesis, N-acetyl-L-cysteine, was provided to cultured cells for 4 h before challenge with ethanol, cytolysis was significantly decreased corresponding with an increase in cellular glutathione content. Pretreatment with diethyl maleate, which depletes reduced glutathione without forming oxidized glutathione, potentiated ethanol-induced cell damage in a dose-dependent manner with the decrease of cellular glutathione content. The administration of tert-butyl hydroperoxide (which is specifically reduced by glutathione peroxidase to generate oxidized glutathione from reduced glutathione) or diamide (which nonenzymatically oxidizes reduced glutathione to oxidized glutathione) enhanced ethanol injury. We conclude that in cultured gastric mucosal cells, (a) intracellular glutathione maintains integrity of gastric mucosal cells against ethanol in vitro; and (b) reduced glutathione rather than oxidized glutathione is responsible for this cytoprotection. We postulate that the presence of reduced glutathione is essential to allow glutathione peroxidase to catalyze the ethanol-generated toxic oxygen radical, hydrogen peroxide.

• OSTI ID: 6721204
• Journal Information: Gastroenterology; (USA), Journal Name: Gastroenterology; (USA) Vol. 98:6; ISSN GASTA; ISSN 0016-5085
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
AMIDES
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL FUNCTIONS
CARBOXYLIC ACIDS
CELL CULTURES
CHEMICAL REACTIONS
CHROMIUM 51
CHROMIUM ISOTOPES
CYSTEINE
DIGESTIVE SYSTEM
DISTRIBUTION
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
ETHANOL
EVEN-ODD NUCLEI
FUNCTIONS
GASTROINTESTINAL TRACT
GLUTATHIONE
HYDROGEN COMPOUNDS
HYDROGEN PEROXIDE
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
MEMBRANES
MUCOUS MEMBRANES
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PEPTIDES
PEROXIDASES
PEROXIDES
POLYPEPTIDES
PROTEINS
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
RATS
REDOX REACTIONS
RODENTS
SUBCELLULAR DISTRIBUTION
THIOLS
TOXICITY
TRACER TECHNIQUES
VERTEBRATES