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

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

OSTI ID:6721204

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

---

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), Vol. 98:6; ISSN 0016-5085
• Country of Publication: United States
• Language: English

Related Subjects

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