Novel Molecular Targets for the Prevention of Fetal Alcohol Syndrome

Martínez, Sergi Robles; Egea, Gustavo

doi:10.2174/157488907779561763

Cited by 18 publications

(14 citation statements)

References 207 publications

(255 reference statements)

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“…Thus, there is extensive evidence to support that alcohol affects a variety of cellular processes in the developing brain through different molecular mechanisms [13,14]. Among these mechanisms, ethanol has been proposed to perturb protein trafficking, including protein glycosylation, exocytosis and endocytosis [14,15-20]. …”

Section: Introductionmentioning

confidence: 99%

Protein Traffic Is an Intracellular Target in Alcohol Toxicity

et al. 2011

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Eukaryotic cells comprise a set of organelles, surrounded by membranes with a unique composition, which is maintained by a complex synthesis and transport system. Cells also synthesize the proteins destined for secretion. Together, these processes are known as the secretory pathway or exocytosis. In addition, many molecules can be internalized by cells through a process called endocytosis. Chronic and acute alcohol (ethanol) exposure alters the secretion of different essential products, such as hormones, neurotransmitters and others in a variety of cells, including central nervous system cells. This effect could be due to a range of mechanisms, including alcohol-induced alterations in the different steps involved in intracellular transport, such as glycosylation and vesicular transport along cytoskeleton elements. Moreover, alcohol consumption during pregnancy disrupts developmental processes in the central nervous system. No single mechanism has proved sufficient to account for these effects, and multiple factors are likely involved. One such mechanism indicates that ethanol also perturbs protein trafficking. The purpose of this review is to summarize our understanding of how ethanol exposure alters the trafficking of proteins in different cell systems, especially in central nervous system cells (neurons and astrocytes) in adult and developing brains.

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Section: Introductionmentioning

confidence: 99%

Protein Traffic Is an Intracellular Target in Alcohol Toxicity

et al. 2011

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“…Among the numerous mechanisms that have been proposed for ethanol (EtOH)-induced teratogenesis, the premise that EtOH alters normal development via disruption of reactive oxygen species (ROS) homeostasis has received considerable research attention and support (Henderson et al, 1999; Martinez and Egea, 2007). In this regard, a number of experimental studies have shown that oxidative stress-induced apoptosis of selected cell populations results from EtOH exposure in embryos, with the induced cell death pattern being predictive of the subsequent defects (Chen and Sulik, 1996; Davis et al, 1990; Heaton et al, 2000; Kotch et al, 1995; Spong et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Reduction of ethanol-induced ocular abnormalities in mice through dietary administration of N-acetylcysteine

Parnell

Sulik

Dehart

et al. 2010

Alcohol

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N-acetylcysteine (NAC) is a derivative of the amino acid L-cysteine that previously has been shown to protect against ethanol (EtOH)-induced apoptosis during early development. Ongoing research is demonstrating that NAC is also proving clinically beneficial in reducing oxidative stress-mediated lung, liver and kidney damage, with protection likely resulting from a NACmediated increase in glutathione levels. In the present study, the hypothesis that co-administration of NAC and EtOH via liquid diet on days 7 and 8 of pregnancy in mice would reduce EtOH's teratogenicity was tested. For this work, adult non-pregnant female mice were acclimated to a liquid diet containing EtOH for 16 days, withdrawn from the EtOH, bred and then returned to the liquid diet containing 4.8% EtOH and/or either 0.5 or 1 mg NAC/ml diet on their 7 th and 8 th days of pregnancy. At the concentrations employed, the mice received NAC dosages of approximately 300 or 600 mg/kg/day and achieved peak blood EtOH levels (BEC) that averaged approximately 200 mg/dl. There was no difference in BEC between the EtOH alone and EtOH plus 600 mg/kg NAC group. Following maternal euthanasia, gestational day (GD) 14 fetuses were removed, fixed, weighed and examined for the presence and severity of ocular abnormalities, a readily assessed endpoint that results from GD 7 and 8 EtOH exposures. While the lower dosage of NAC (300 mg/ kg) resulted in a decrease in the incidence of ocular defects in both the left and right eyes, this reduction was not statistically significant. However, doubling the NAC concentration did yield a significant change; as compared to the group treated with EtOH alone, the incidence of ocular abnormalities was diminished by 22%. These results show the potential of an orally administered compound with proven clinical efficacy to reduce EtOH's teratogenic effects and support the premise that oxidative damage plays an important mechanistic role in Fetal Alcohol Spectrum Disorders.

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“…Nutritional supplementation may also mitigate alcohol's teratogenic effects. Nutritional supplements may compensate for changes in the bioavailability of Extracted from Martinez and Egea (2007). nutrients due to alcohol metabolism (Lieber, 2000).…”

Section: Discussionmentioning

confidence: 99%

Advances in the development of novel antioxidant therapies as an approach for fetal alcohol syndrome prevention

Joya

Garcı́a-Algar

Salat-Batlle

et al. 2014

Birth Defects Research

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Ethanol is the most common human teratogen, and its consumption during pregnancy can produce a wide range of abnormalities in infants known as fetal alcohol spectrum disorder (FASD). The major characteristics of FASD can be divided into: (i) growth retardation, (ii) craniofacial abnormalities, and (iii) central nervous system (CNS) dysfunction. FASD is the most common cause of nongenetic mental retardation in Western countries. Although the underlying molecular mechanisms of ethanol neurotoxicity are not completely determined, the induction of oxidative stress is believed to be one central process linked to the development of the disease. Currently, there is no known effective strategy for prevention (other than alcohol avoidance) or treatment. In the present review we will provide the state of art in the evidence for the use of antioxidants as a potential therapeutic strategy for the treatment using whole-embryo and culture cells models of FASD. We conclude that the imbalance of the intracellular redox state contributes to the pathogenesis observed in FASD models, and we suggest that antioxidant therapy can be considered a new efficient strategy to mitigate the effects of prenatal ethanol exposure.

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Novel Molecular Targets for the Prevention of Fetal Alcohol Syndrome

Cited by 18 publications

References 207 publications

Protein Traffic Is an Intracellular Target in Alcohol Toxicity

Protein Traffic Is an Intracellular Target in Alcohol Toxicity

Reduction of ethanol-induced ocular abnormalities in mice through dietary administration of N-acetylcysteine

Advances in the development of novel antioxidant therapies as an approach for fetal alcohol syndrome prevention

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