Neonatal alcohol exposure increases malondialdehyde (MDA) and glutathione (GSH) levels in the developing cerebellum.

It has been suggested that developmental alcohol-induced brain damage is mediated through increases in oxidative stress. In this study, the concentrations of malondialdehyde (MDA) and reduced glutathione (GSH) were measured to indicate alcohol-mediated oxidative stress. In addition, the ability of two known antioxidants, melatonin (MEL) and lazaroid U-83836E (U), to attenuate alcohol-induced oxidative stress was investigated. Sprague-Dawley rat pups were randomly assigned to six artificially-reared groups, ALC (alcohol), MEL, MEL/ALC, U, U/ALC, and GC (gastrostomy control), and one normal suckle control (to control for artificial-rearing effects on the dependent variables). The daily dosages for ALC, MEL, and U were 6 g/kg, 20 mg/kg, and 20 mg/kg, respectively. Alcohol was administered in 2 consecutive feedings, and antioxidant (MEL or U) was administered for a total of 4 consecutive feedings (2 feedings prior to and 2 feedings concurrently with alcohol). The animals received treatment from postnatal days (PD) 4 through 9. Cerebellar, hippocampal, and cortical samples were collected on PD 9 and analyzed for MDA and GSH content. The results indicated that MDA concentrations in the cerebellum were significantly elevated in animals receiving alcohol; however, MDA levels in the hippocampus and cortex were not affected by alcohol treatment. Additionally, GSH levels in the cerebellum were significantly elevated in groups receiving alcohol, regardless of antioxidant treatment. Neither antioxidant was able to protect against alcohol-induced alterations of MDA or GSH. These findings suggest that alcohol might increase GSH levels indirectly as a compensatory mechanism designed to protect the brain from oxidative-stress-mediated insult.