ReviewThe role of oxidative stress in fetal alcohol spectrum disorders

The ingestion of alcohol/ethanol during pregnancy can result in abnormal fetal development in both humans and a variety of experimental animal models. Depending on the pattern of consumption, the dose, and the period of exposure to ethanol, a myriad of structural and functional deficits can be observed. These teratogenic effects are thought to result from the ethanol-induced dysregulation of a variety of intracellular pathways ultimately culminating in toxicity and cell death. For instance, ethanol exposure can lead to the generation of reactive oxygen species (ROS) and produce an imbalance in the intracellular redox state, leading to an overall increase in oxidative stress. In the present review we will provide an up-to-date summary on the effects of prenatal/neonatal ethanol exposure on the levels of oxidative stress in the central nervous system (CNS) of experimental models of fetal alcohol spectrum disorders (FASD). We will also review the evidence for the use of antioxidants as potential therapeutic strategies for the treatment of some of the neuropathological deficits characteristic of both rodent models of FASD and children afflicted with these disorders. We conclude that an imbalance in the intracellular redox state contributes to the deficits seen in FASD and suggest that antioxidants are potential candidates for the development of novel therapeutic strategies for the treatment of these developmental disorders.

Research highlight► Ethanol metabolism results in the production of reactive oxygen species. ► Reactive oxygen species can lead to oxidative stress and neuronal cell death. ► Oxidative stress contributes to deficits seen in fetal alcohol spectrum disorders. ► Antioxidants are candidates for the treatment of developmental disorders.