Neurotoxic Effects of Alcohol and Acetaldehyde During Embryonic Development

Abstract

Alcohol drinking during pregnancy results in abnormal fetal development, including fetal alcohol syndrome (FAS) in humans and experimental animals. FAS is characterized by two major effects, including central nervous system (CNS) dysfunction and multiple anomalies recognizable mainly as a typical face. However, the mechanisms of alcohol-induced embryotoxicity have not been clearly demonstrated. The aim of the present study was to investigate the possible mechanisms underlying ethanol-induced FAS in the developing embryo. First, ethanol-induced developmental abnormalities were investigated in vitro. Postimplantation embryos at gestation day (GD) 9.5 were cultured for 48 h and observed for morphological changes. Ethanol-mediated changes in proteins regulated apoptosis (p53 and bcl-2), antioxidant (vitamin E and catalase) activities, generation of reactive oxygen species (ROS), and oxidative DNA damage shown as 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured in embryonic midbrain cells. Alcohol or acetaldehyde significantly induced cytotoxicity in cultured rat embryonic midbrain cells. The levels of p53, bcl-2, and 8-OHdG were concomitantly changed by alcohol and acetaldehyde treatment in midbrain cells. Injured cells induced by ROS were increased by alcohol or acetaldehyde treatment in midbrain cells. Cotreatment with alcohol or acetaldehyde and catalase decreased cytotoxicity in midbrain cells. In postimplantation embryo culture, alcohol or acetaldehyde-treated embryos showed retardation of embryonic growth and development in a concentration-dependent manner. These results indicate that alcohol and its metabolite acetaldehyde induce fetal developmental abnormalities by disrupting cellular differentiation and growth. Data demonstrate that some antioxidants can partially protect against the alcohol-induced embryonic developmental toxicity.

Estrogen modulation of the ethanol-evoked myocardial oxidative stress and dysfunction via DAPK3/Akt/ERK activation in male rats

“…More importantly, we have recently shown that microinjection of ethanol into the rostral ventrolateral medulla of spontaneously hypertensive rats, which exhibits higher catalase activity than its control counterpart, results in a greater pressor response, and the latter was attenuated by prior inhibition of local catalase activity (El-Mas and Abdel-Rahman, 2012a). In addition to its role in ethanol cardiovascular toxicity, acetaldehyde has also been implicated in behavioral, reinforcing, and neurotoxic effects of ethanol (Lee et al, 2005; Pastor et al, 2008; Karahanian et al, 2011). It should be remembered, however, that the expected rise in acetaldehyde formation due to heightened catalase and alcohol dehydrogenase activities might be counterbalanced by the concomitant increases in mitALDH2 activity (Fig.…”

The Neuronal Nitric Oxide Synthase (nNOS) Gene and Neuroprotection Against Alcohol Toxicity

“…Both alcohol and acetaldehyde are toxic for the embryo and fetus (Lee et al, 2005). Thus, it stands to reason that the more rapidly these harmful substances are cleared from the body, the less injurious the ingestion of alcohol will be.…”

Fetal Alcohol Spectrum Disorders

“…The results of such studies to date have been mixed but demonstrate that some antioxidants can partially protect against alcoholinduced developmental damage (Da Lee et al 2005). Another important functional system altered by prenatal alcohol exposure is the L1 cell adhesion system.…”