Increased hepatic efflux of glutathione after chronic ethanol feeding

Jeffrey L. Pierson, Mack C. Mitchell

Research output: Contribution to journalArticle

Abstract

Chronic ethanol feeding increases hepatotoxicity of drugs, such as acetaminophen, which form electrophilic metabolites. Availability of glutathione (GSH) is important in preventing liver damage from reactive metabolites. Chronic ethanol feeding has been reported to increase turnover of hepatic GSH in rats. The results of the present study show that the total hepatic efflux of GSH was increased from 5.95 ± 0.42 nmoles/min/g liver (control) to 9.96 ± 0.57 nmoles/min/g (P <0.001) in isolated perfused livers from rats 24 hr after withdrawal from chronic ethanol feeding. The increase in total efflux of GSH was due to a significant increase in sinusoidal GSH efflux from 4.76 ± 0.49 nmoles/min/g liver in control rats to 9.07 ± 0.47 nmoles/min/g (P <0.001) in ethanol-fed rats, while biliary efflux decreased slightly, 1.20 ± 0.11 (control) vs 0.89 ± 0.31 (ethanol). The increase in cellular efflux of GSH was similar in magnitude to the increase in hepatic GSH turnover that we reported previously. Biliary GSSG was similar in both groups of animals. Hepatic GGT activity was increased slightly, but not significantly, whereas renal GGT activity was similar in ethanol-fed rats. Hepatic GSH and GSSG levels were also similar. The increase in turnover of hepatic GSH in rats withdrawn from chronic ethanol feeding was most likely due to increased cellular efflux of GSH. This finding suggests that chronic ethanol feeding may increase cellular requirements for GSH, although the mechanism remains unknown. This alteration in GSH turnover may have important consequences for detoxification of xenobiotics or their metabolites by the liver.

Original languageEnglish (US)
Pages (from-to)1533-1537
Number of pages5
JournalBiochemical Pharmacology
Volume35
Issue number9
DOIs
StatePublished - May 1 1986

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Glutathione
Ethanol
Liver
Rats
Metabolites
Glutathione Disulfide
Rat control
Detoxification
Xenobiotics
Acetaminophen
Animals
Availability
Kidney
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology

Cite this

Increased hepatic efflux of glutathione after chronic ethanol feeding. / Pierson, Jeffrey L.; Mitchell, Mack C.

In: Biochemical Pharmacology, Vol. 35, No. 9, 01.05.1986, p. 1533-1537.

Research output: Contribution to journalArticle

Pierson, Jeffrey L. ; Mitchell, Mack C. / Increased hepatic efflux of glutathione after chronic ethanol feeding. In: Biochemical Pharmacology. 1986 ; Vol. 35, No. 9. pp. 1533-1537.
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