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Glutathione Protects the Developing Heart from Defects and Global DNA Hypomethylation Induced by Prenatal Alcohol Exposure.
- Source :
-
Alcoholism, clinical and experimental research [Alcohol Clin Exp Res] 2021 Jan; Vol. 45 (1), pp. 69-78. Date of Electronic Publication: 2021 Jan 02. - Publication Year :
- 2021
-
Abstract
- Background: Fetal alcohol spectrum disorder (FASD) is caused by prenatal alcohol exposure (PAE), the intake of ethanol (C <subscript>2</subscript> H <subscript>5</subscript> OH) during pregnancy. Features of FASD cover a range of structural and functional defects including congenital heart defects (CHDs). Folic acid and choline, contributors of methyl groups to one-carbon metabolism (OCM), prevent CHDs in humans. Using our avian model of FASD, we have previously reported that betaine, another methyl donor downstream of choline, prevents CHDs. The CHD preventions are substantial but incomplete. Ethanol causes oxidative stress as well as depleting methyl groups for OCM to support DNA methylation and other epigenetic alterations. To identify more compounds that can safely and effectively prevent CHDs and other effects of PAE, we tested glutathione (GSH), a compound that regulates OCM and is known as a "master antioxidant."<br />Methods/results: Quail embryos injected with a single dose of ethanol at gastrulation exhibited congenital defects including CHDs similar to those identified in FASD individuals. GSH injected simultaneously with ethanol not only prevented CHDs, but also improved survival and prevented other PAE-induced defects. Assays of hearts at 8 days (HH stage 34) of quail development, when the heart normally has developed 4-chambers, showed that this single dose of PAE reduced global DNA methylation. GSH supplementation concurrent with PAE normalized global DNA methylation levels. The same assays performed on quail hearts at 3 days (HH stage 19-20) of development, showed no difference in global DNA methylation between controls, ethanol-treated, GSH alone, and GSH plus ethanol-treated cohorts.<br />Conclusions: GSH supplementation shows promise to inhibit effects of PAE by improving survival, reducing the incidence of morphological defects including CHDs, and preventing global hypomethylation of DNA in heart tissues.<br /> (© 2020 by the Research Society on Alcoholism.)
- Subjects :
- Alcohol Drinking adverse effects
Animals
Central Nervous System Depressants adverse effects
Drug Evaluation, Preclinical
Ethanol adverse effects
Female
Glutathione pharmacology
Heart Defects, Congenital chemically induced
Pregnancy
Quail
DNA Methylation drug effects
Fetal Alcohol Spectrum Disorders prevention & control
Glutathione therapeutic use
Heart Defects, Congenital prevention & control
Prenatal Exposure Delayed Effects
Subjects
Details
- Language :
- English
- ISSN :
- 1530-0277
- Volume :
- 45
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Alcoholism, clinical and experimental research
- Publication Type :
- Academic Journal
- Accession number :
- 33206417
- Full Text :
- https://doi.org/10.1111/acer.14511