Effects of In Utero Administration of Alcohol on Glutathione Levels in Brain and Liver

Reyes, Edward; Ott, Stephnine; Robinson, Barbara L.

doi:10.1111/j.1530-0277.1993.tb00857.x

Cited by 51 publications

(16 citation statements)

References 37 publications

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“…Both of these reductions have been used as parameters of oxidative stress and have been attributed to enhanced pro-oxidant activity within the brain [4,5,20,26,32,34]. The especial vulnerability of the striatum to ethanol-effected pro-oxidant and metabolic changes has been noted before [5,41 ], and may relate to the high dopamine content of this region which makes it prone to oxidative and excitotoxic damage [ 12].…”

Section: Discussionmentioning

confidence: 99%

Effect of an NMDA receptor antagonist and a ganglioside GM1 derivative upon ethanol-induced modification of parameters of oxidative stress in several brain regions

Bondy

Guo

1996

Brain Research

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Dietary administration of ethanol to rats for 2 weeks was able to depress levels of glutathione (GSH) and Cu/Zn superoxide dismutase (SOD) in several brain regions. This was indicative of the generation of excess levels of reactive oxygen in treated animals. The potentially protective effect of both an NMDA receptor blocker (MK-80 I) and an internally esterified derivative of ganglioside GM 1 (AGF 2 ) upon ethanol-induced changes in these indices of oxidative stress. was studied. Both of these agents are reported to have neuroprotective properties, but neither was able to prevent ethanol-induced reduction of GSH and SOD levels in any brain area studied. In fact, both agents depressed SOD and GSH levels in midbrain independently of ethanol. MK-80 I had a pronounced pro-oxidant potential, and when administered in combination with ethanol, GSH and SOD were reduced in midbrain and striatum to levels below those obtained with either agent alone. The pro-oxidant properties of ethanol may thus act independently of its actions upon the NMDA receptor. The protective properties of NMDA receptor inhibitors or gangliosides cannot be attributed to any antioxidant effect.

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Section: Discussionmentioning

confidence: 99%

Effect of an NMDA receptor antagonist and a ganglioside GM1 derivative upon ethanol-induced modification of parameters of oxidative stress in several brain regions

Bondy

Guo

1996

Brain Research

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“…It has been suggested that chronic EtOH feeding reduces the entry of cytosolic GSH into mitochondria and that the decreased mitochondrial pool size of GSH results in reduced GPx activity (25). Perinatal EtOH is known to increase systemic oxidative stress in developing organs, particularly the liver and the brain (18,32,33,41,55). There have been reports of EtOH-associated oxidative stress in the hippocampus and other brain regions where postnatal EtOH decreased GSH content and increased lipid peroxides and protein carbonyls with brain region and age-dependent differences in EtOH sensitivity and the response of antioxidant enzymes (29,32,33,41,55).…”

Section: Discussionmentioning

confidence: 99%

“…Perinatal EtOH is known to increase systemic oxidative stress in developing organs, particularly the liver and the brain (18,32,33,41,55). There have been reports of EtOH-associated oxidative stress in the hippocampus and other brain regions where postnatal EtOH decreased GSH content and increased lipid peroxides and protein carbonyls with brain region and age-dependent differences in EtOH sensitivity and the response of antioxidant enzymes (29,32,33,41,55). For example, Heaton et al (32) reported that 7-day-old rats postnatally exposed to EtOH had delayed SOD and catalase responses compared with 21-day-old rats and concluded that older brains have protective mechanisms against EtOH.…”

Section: Discussionmentioning

confidence: 99%

Intrauterine ethanol exposure results in hypothalamic oxidative stress and neuroendocrine alterations in adult rat offspring

Dembele

Yao²,

Chen³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Dembele, Korami, Xing-Hai Yao, Li Chen and B. L. Grégoire Nyomba. Intrauterine ethanol exposure results in hypothalamic oxidative stress and neuroendocrine alterations in adult rat offspring. Am J Physiol Regul Integr Comp Physiol 291: R796 -R802, 2006. First published April 13, 2006 doi:10.1152/ajpregu.00633.2005 exposure is associated with low birth weight, followed by increased appetite, catch-up growth, insulin resistance, and impaired glucose tolerance in the rat offspring. Because EtOH can induce oxidative stress, which is a putative mechanism of insulin resistance, and because of the central role of the hypothalamus in the regulation of energy homeostasis and insulin action, we investigated whether prenatal EtOH exposure causes oxidative damage to the hypothalamus, which may alter its function. Female rats were given EtOH by gavage throughout pregnancy. At birth, their offspring were smaller than those of non-EtOH rats. Markers of oxidative stress and expression of neuropeptide Y and proopiomelanocortin (POMC) were determined in hypothalami of postnatal day 7 (PD7) and 3-mo-old (adult) rat offspring. In both PD7 and adult rats, prenatal EtOH exposure was associated with decreased levels of glutathione and increased expression of MnSOD. The concentrations of lipid peroxides and protein carbonyls were normal in PD7 EtOH-exposed offspring, but were increased in adult EtOH-exposed offspring. Both PD7 and adult EtOH-exposed offspring had normal neuropeptide Y and POMC mRNA levels, but the adult offspring had reduced POMC protein concentration. Thus only adult offspring preexposed to EtOH had increased hypothalamic tissue damage and decreased levels of POMC, which could impair melanocortin signaling. We conclude that prenatal EtOH exposure causes hypothalamic oxidative stress, which persists into adult life and alters melanocortin action during adulthood. These neuroendocrine alterations may explain weight gain and insulin resistance in rats exposed to EtOH early in life.

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“…A decrease in the antioxidant GSH has been demonstrated, particularly in the alcohol-exposed fetal liver (9,15,16). As an essential antioxidant in the body, GSH is normally present in high concentrations in the ELF of the lung (17).…”

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confidence: 99%

Fetal Alcohol Exposure Impairs Alveolar Macrophage Function via Decreased Glutathione Availability

et al. 2005

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Immature function of the alveolar macrophage increases the risk of pulmonary infections in premature newborns. In utero alcohol increases fetal systemic oxidative stress. Because the premature lung is deficient in glutathione (GSH), we hypothesized that chronic in utero alcohol (ethanol) exposure exacerbates the oxidative stress within the developing lung, thereby impairing alveolar macrophage function. Additionally, we evaluated the effects of in vivo and in vitro GSH availability on ethanol-exposed macrophage function. Using a guinea pig model of chronic in utero ethanol exposure, fetal epithelial lining fluid (ELF) and alveolar macrophage GSH were decreased with increased markers of oxidative stress. Ethanol-exposed macrophage exhibited impaired phagocytosis and increased apoptosis compared with gestational control. When the GSH precursor S-adenosyl-methionine (SAM) was added to the maternal drinking water containing ethanol, fetal ELF and macrophage GSH were maintained and ELF oxidative stress diminished. In vivo maternal SAM therapy maintained macrophage phagocytosis and decreased apoptosis. In vitro GSH supplements also improved phagocytosis and viability in both premature and ethanolexposed macrophage. This suggested that in utero ethanol impaired premature macrophage function and viability via decreased GSH availability. Furthermore, GSH supplementation during and after ethanol exposure improved fetal macrophage function and viability. These results add a new dimension to the detrimental effects of fetal alcohol exposure on the developing alveolar macrophage, raising the possibility of GSH therapy to augment premature alveolar macrophage function. Fetal alcohol exposure remains a significant problem in our society. Alcohol abuse and binge drinking by pregnant women has been estimated at an alarming 35% of pregnancies (1-3). Fetal alcohol syndrome or alcohol-related neurodevelopmental disorder has been estimated to occur in ‫0001/1ف‬ pregnancies (4). Because there is a strong relationship between cocaine abuse and concurrent alcohol ingestion (5-7), and both substances may increase the risk of premature delivery (7,8), a significant population of premature infants is exposed to alcohol in utero.In animal models of fetal alcohol exposure, alcohol increases systemic oxidative stress in the developing fetus (9 -14). A decrease in the antioxidant GSH has been demonstrated, particularly in the alcohol-exposed fetal liver (9,15,16). As an essential antioxidant in the body, GSH is normally present in high concentrations in the ELF of the lung (17). The fetal lung is at risk for increased oxidative stress during development, because maturation of antioxidant systems, including GSH, is gestationally dependent (18,19). A reduction in alveolar GSH, as seen in the premature infant, leaves the preterm lung susceptible to increased pulmonary oxidative injury (20,21) and chronic lung disease (18,22). The impact of the oxidative stress of fetal alcohol exposure superimposed on the low GSH environment of the developing lu...

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Effects of In Utero Administration of Alcohol on Glutathione Levels in Brain and Liver

Cited by 51 publications

References 37 publications

Effect of an NMDA receptor antagonist and a ganglioside GM1 derivative upon ethanol-induced modification of parameters of oxidative stress in several brain regions

Effect of an NMDA receptor antagonist and a ganglioside GM1 derivative upon ethanol-induced modification of parameters of oxidative stress in several brain regions

Intrauterine ethanol exposure results in hypothalamic oxidative stress and neuroendocrine alterations in adult rat offspring

Fetal Alcohol Exposure Impairs Alveolar Macrophage Function via Decreased Glutathione Availability

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