Factors involved in hepatic glutathione depletion induced by acute ethanol administration

被引:28
作者
Choi, DW [1 ]
Kim, SY [1 ]
Kim, SK [1 ]
Kim, YC [1 ]
机构
[1] Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea
关键词
D O I
10.1080/00984100050079520
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Factors implicated in changes of the hepatic glutathione concentration following acute ethanol administration were examined in rats. Adult female rats were treated with either ethanol (4 g/kg, po) or an isocaloric glucose solution. The hepatic reduced glutathione (GSH) concentration decreased rapidly after ethanol intake with a maximum diminution, approximately 50% of the control value, being observed at t = 6 h. The hepatic GSH concentration gradually increased, and finally rebounded at 24 h after ethanol ingestion. The dose of ethanol induced a transient increase in the oxidized glutathione (GSSG) and GSSG/GSH ratio, which was associated with a significant reduction in GSH rather t han elevation in GSSG. The activity of gamma-glutamylcysteine synthetase (GCS), the rate-limiting enzyme for glutathione synthesis, and the cysteine concentration in liver were also measured. The GCS activity was depressed to approximately 80% of the control value at t = 2.5 h followed by rapid recovery, but no difference in the hepatic cysteine concentration between control and ethanol treated rats was observed for 24 h, suggesting that the reduction in glutathione synthesis may not play a major role in the significant depletion of this tripeptide in liver. The total glutathione concentration was measured both in prehepatic and posthepatic inferior vena cava blood. The glutathione concentration in posthepatic blood was approximately twice as high as that of prehepatic blood in control rats. Acute ethanol administration doubled the elevation of glutathione in posthepatic blood measured at t = 2.5 h. The sinusoidal efflux of glutathione estimated from the increase in blood glutathione concentration was greater than the total amount of its depletion in the liver of rats treated with ethanol. The results suggest that in the liver of rats treated acutely with ethanol, glutathione efflux plays the most important role in the reduction of this tripeptide, which would be aggravated by a transient decrease in glutathione synthesis and by increased consumption in association with its metabolism.
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页码:459 / 469
页数:11
相关论文
共 30 条
[1]   INORGANIC-PHOSPHATE ASSAY WITH MALACHITE GREEN - AN IMPROVEMENT AND EVALUATION [J].
CARTER, SG ;
KARL, DW .
JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS, 1982, 7 (01) :7-13
[2]   PHYSIOLOGICAL-PARAMETERS IN LABORATORY-ANIMALS AND HUMANS [J].
DAVIES, B ;
MORRIS, T .
PHARMACEUTICAL RESEARCH, 1993, 10 (07) :1093-1095
[3]   ASSAY, PURIFICATION, PROPERTIES AND MECHANISM OF ACTION OF GAMMA-GLUTAMYLCYSTEINE SYNTHETASE FROM LIVER OF RAT AND XENOPUS-LAEVIS [J].
DAVIS, JS ;
BALINSKY, JB ;
HARINGTON, JS ;
SHEPHERD, JB .
BIOCHEMICAL JOURNAL, 1973, 133 (04) :667-678
[4]   CIRCADIAN PERIODICITY OF TISSUE GLUTATHIONE AND ITS RELATIONSHIP WITH LIPID-PEROXIDATION IN RATS [J].
FAROOQUI, MYH ;
AHMED, AE .
LIFE SCIENCES, 1984, 34 (24) :2413-2418
[5]   EFFECT OF CHRONIC ETHANOL FEEDING ON RAT HEPATOCYTIC GLUTATHIONE - COMPARTMENTATION, EFFLUX, AND RESPONSE TO INCUBATION WITH ETHANOL [J].
FERNANDEZCHECA, JC ;
OOKHTENS, M ;
KAPLOWITZ, N .
JOURNAL OF CLINICAL INVESTIGATION, 1987, 80 (01) :57-62
[6]   EFFECTS OF CHRONIC ETHANOL FEEDING ON RAT HEPATOCYTIC GLUTATHIONE - RELATIONSHIP OF CYTOSOLIC GLUTATHIONE TO EFFLUX AND MITOCHONDRIAL SEQUESTRATION [J].
FERNANDEZCHECA, JC ;
OOKHTENS, M ;
KAPLOWITZ, N .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (04) :1247-1252
[8]   INFLUENCE OF ACUTE ETHANOL ADMINISTRATION ON HEPATIC GLUTATHIONE METABOLISM IN THE RAT [J].
GONZALEZ, J ;
MUNOZ, ME ;
MARTIN, MI ;
COLLADO, PS ;
FERMOSO, J ;
ESTELLER, A .
ALCOHOL, 1988, 5 (02) :103-106
[10]   CHANGES IN GLUTATHIONE IN ACUTE AND CHRONIC ALCOHOL-INTOXICATION [J].
GUERRI, C ;
GRISOLIA, S .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1980, 13 :53-61