Protective Role of Ellagic Acid Against Ethanol-Induced Neurodevelopmental Disorders in Newborn Male Rats: Insights into Maintenance of Mitochondrial Function and Inhibition of Oxidative Stress.

OBJECTIVE

Ellagic acid (EA) exerts neuroprotective, mitoprotective, anti-oxidative, and anti-inflammatory effects. We evaluated the protective effect of EA on ethanol-induced fetal alcohol spectrum disorders (FASD).

METHOD: A total of 35 newborn male rats were used, divided into five groups, including control (normal saline), ethanol (5.25 g/kg per day), ethanol (5.25 g/kg per day) + EA (10 mg/kg), ethanol (5.25 g/kg per day) + EA (20 mg/kg), and ethanol (5.25 g/kg per day) + EA (40 mg/kg). Thirty-six days after birth, behavioral tests (Morris water maze and Elevated Plus Maze), tumor necrosis factor-alpha (TNF-alpha) levels, oxidative markers (malondialdehyde, glutathione, and superoxide dismutase), and mitochondrial examination such as succinate dehydrogenases activity, mitochondrial swelling, mitochondrial membrane potential, and reactive oxygen species formation were analyzed.

RESULTS

The results revealed that ethanol exposure adversely affected cognitive and mitochondrial functions and induced oxidative stress and inflammation in brain tissue. However, EA (20 and 40 mg/kg) administration effectively prevented the toxic effects of ethanol in the FASD model.

CONCLUSIONS

These findings demonstrate that ethanol application significantly impairs brain development via mitochondrial dysfunction and induction of oxidative stress. These data indicate that EA might be a useful compound for the prevention of alcohol-induced FASD.