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

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 mo (young), 12 mo (mature), and 24 mo (old); and GSH and cyst(e)ine concentrations were measured 0-24 hours thereafter. EtOH administration (5g/kg) depleted hepatic GSH levels >50% by 6 hr in all animals. By 24 hr, levels remained low in both young and old mice, but recovered to baseline levels in mature mice. At 6 hr, the decrease in hepatic GSH was dosedependent 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.

Diallyl trisulfide (DATS) effectively attenuated oxidative stress-mediated liver injury and hepatic mitochondrial dysfunction in acute ethanol-exposed mice

“…Speisky et al (1985) found a 35% decrease of the hepatic GSH content at 5 h after administration of ethanol (4 g/kg bw). A recent study conducted by Vogt and Richie (2007) showed that ethanol (5 mg/kg bw) resulted in the significant GSH decrease at 2 and 6 h after exposure, which recovered to the normal level at 24 h. In our study, GSH decreased slightly but had statistical significance in liver tissue homogenate (P < 0.05). The smaller decline might be associated with the examination time.…”

Effects of astaxanthin on antioxidant capacity of golden pompano (Trachinotus ovatus) in vivo and in vitro

“…One mechanism for oxidative stress induced GSH depletion may involve enhanced utilization of GSH for the detoxification of free radicals and other oxidants produced as a result of H 2 O 2 exposure (Shaw 1989). Vogt suggested that the increase of lipid peroxidation was not apparent until after GSH levels had been depleted (Vogt and Richie 2007). Astaxanthin can improve the GSH content in both our in vivo and in vitro study.…”

A comparative study on effect of continuous radon inhalation on several-time acute alcohol-induced oxidative damages of liver and brain in mouse

“…Acetaldehyde, which is a metabolic product of alcohol, is one substance that reacts with GSH. Alcohol administration leads to GSH depletion in liver and other tissues, 27,28) suggesting direct conjugation of GSH with acetaldehyde and reactive intermediates of alcohol oxidation. 29,30) Other mechanisms by which alcohol induces hepatic GSH depletion include alcohol-induced increased efflux of GSH from the liver 31,32) and enhanced utilization of GSH for detoxification of ROS produced as a result of alcohol administration.…”