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Toxicol Lett. 2010 Mar 1;193(1):94-100. doi: 10.1016/j.toxlet.2009.12.012. Epub 2009 Dec 21.

The role of NOX enzymes in ethanol-induced oxidative stress and apoptosis in mouse embryos.

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1
Bowles Center for Alcohol Studies, Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7178, USA.

Abstract

Reactive oxygen species (ROS) play an important role in ethanol-induced apoptosis and teratogenesis. However, the major sources of ROS in ethanol-exposed embryos have remained undefined. This study was conducted to determine the role of NADPH oxidase (NOX) in ethanol-induced oxidative stress and apoptosis in mouse embryos. Analyses of mRNA expression indicated that ethanol treatment resulted in a significant increase in mRNA expression of NOX catalytic subunit Duox-1 in gestational day 9 (GD 9:0) mouse embryos. Ethanol exposure also resulted in significant increases in mRNA expression of NOX regulatory subunits, p22phox, p67phox, NOXA1 and NOXO1. In addition, a significant increase in NOX enzyme activity was found in the ethanol-exposed embryos as compared to controls. Co-treatment with the NOX inhibitor, diphenyleneiodonium (DPI), significantly prevented ethanol-induced increases in NOX enzyme activity, ROS generation and oxidative DNA damage in ethanol-exposed embryos. DPI treatment also resulted in a reduction in caspase-3 activation, decreased caspase-3 activity and diminished prevalence of apoptosis in ethanol-exposed embryos. These results support the hypothesis that NOX is a critical source of ROS in ethanol-exposed embryos and that it plays an important role in ethanol-induced oxidative stress and pathogenesis.

PMID:
20026259
PMCID:
PMC2822117
DOI:
10.1016/j.toxlet.2009.12.012
[Indexed for MEDLINE]
Free PMC Article

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