Glutathione depletion and recovery after acute ethanol administration in the aging mouse

Barbara L. Vogt, John Richie

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Glutathione (GSH) plays an important role in the detoxification of ethanol (EtOH) and acute EtOH administration leads to GSH depletion in the liver and other tissues. Aging is also associated with a progressive decline in GSH levels and impairment in GSH biosynthesis in many tissues. Thus, the present study was designed to examine the effects of aging on EtOH-induced depletion and recovery of GSH in different tissues of the C57Bl/6NNIA mouse. EtOH (2-5 g/kg) or saline was administered i.p. to mice of ages 6 months (young), 12 months (mature), and 24 months (old); and GSH and cyst(e)ine concentrations were measured 0-24 h thereafter. EtOH administration (5 g/kg) depleted hepatic GSH levels >50% by 6 h in all animals. By 24 h, levels remained low in both young and old mice, but recovered to baseline levels in mature mice. At 6 h, the decrease in hepatic GSH was dose-dependent up to 3 g/kg EtOH, but not at higher doses. The extent of depletion at the 3 g/kg dose was dependent upon age, with old mice demonstrating significantly lower GSH levels than mature mice (P < 0.001). Altogether these results indicate that aging was associated with a greater degree of EtOH and fasting-induced GSH depletion and subsequent impaired recovery in liver. An impaired ability to recover was also observed in young animals. Further studies are required to determine if an inability to recover from GSH depletion by EtOH is associated with enhanced toxicity.

Original languageEnglish (US)
Pages (from-to)1613-1621
Number of pages9
JournalBiochemical Pharmacology
Volume73
Issue number10
DOIs
StatePublished - May 15 2007

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Glutathione
Ethanol
Aging of materials
Tissue
Recovery
Liver
Animals
Detoxification
Biosynthesis
Toxicity
Aptitude
Cysts
Fasting

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

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abstract = "Glutathione (GSH) plays an important role in the detoxification of ethanol (EtOH) and acute EtOH administration leads to GSH depletion in the liver and other tissues. Aging is also associated with a progressive decline in GSH levels and impairment in GSH biosynthesis in many tissues. Thus, the present study was designed to examine the effects of aging on EtOH-induced depletion and recovery of GSH in different tissues of the C57Bl/6NNIA mouse. EtOH (2-5 g/kg) or saline was administered i.p. to mice of ages 6 months (young), 12 months (mature), and 24 months (old); and GSH and cyst(e)ine concentrations were measured 0-24 h thereafter. EtOH administration (5 g/kg) depleted hepatic GSH levels >50{\%} by 6 h in all animals. By 24 h, levels remained low in both young and old mice, but recovered to baseline levels in mature mice. At 6 h, the decrease in hepatic GSH was dose-dependent up to 3 g/kg EtOH, but not at higher doses. The extent of depletion at the 3 g/kg dose was dependent upon age, with old mice demonstrating significantly lower GSH levels than mature mice (P < 0.001). Altogether these results indicate that aging was associated with a greater degree of EtOH and fasting-induced GSH depletion and subsequent impaired recovery in liver. An impaired ability to recover was also observed in young animals. Further studies are required to determine if an inability to recover from GSH depletion by EtOH is associated with enhanced toxicity.",
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Glutathione depletion and recovery after acute ethanol administration in the aging mouse. / Vogt, Barbara L.; Richie, John.

In: Biochemical Pharmacology, Vol. 73, No. 10, 15.05.2007, p. 1613-1621.

Research output: Contribution to journalArticle

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AB - Glutathione (GSH) plays an important role in the detoxification of ethanol (EtOH) and acute EtOH administration leads to GSH depletion in the liver and other tissues. Aging is also associated with a progressive decline in GSH levels and impairment in GSH biosynthesis in many tissues. Thus, the present study was designed to examine the effects of aging on EtOH-induced depletion and recovery of GSH in different tissues of the C57Bl/6NNIA mouse. EtOH (2-5 g/kg) or saline was administered i.p. to mice of ages 6 months (young), 12 months (mature), and 24 months (old); and GSH and cyst(e)ine concentrations were measured 0-24 h thereafter. EtOH administration (5 g/kg) depleted hepatic GSH levels >50% by 6 h in all animals. By 24 h, levels remained low in both young and old mice, but recovered to baseline levels in mature mice. At 6 h, the decrease in hepatic GSH was dose-dependent up to 3 g/kg EtOH, but not at higher doses. The extent of depletion at the 3 g/kg dose was dependent upon age, with old mice demonstrating significantly lower GSH levels than mature mice (P < 0.001). Altogether these results indicate that aging was associated with a greater degree of EtOH and fasting-induced GSH depletion and subsequent impaired recovery in liver. An impaired ability to recover was also observed in young animals. Further studies are required to determine if an inability to recover from GSH depletion by EtOH is associated with enhanced toxicity.

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