Chronic administration of an alcohol diet enhanced CYP2E1 protein expression in rat brain tissues [32,33]. Upadhya and colleagues demonstrated the constitutive expression of CYP2E1 protein in neurons within cerebral cortex, Purkinje, or granule cell layers of cerebellum, and induction of CYP2E1 protein level in the cortex of rat or human brain after chronic ethanol consumption [34]. We demonstrated the induction of CYP2E1 activity after EtOH exposure in primary human brain endothelial cells paralleling elevated ROS production and BBB dysfunction [12,13,15]. BBB dysfunction could be important to neurological disorders in the context of FWH reaction within the endothelium and copper deficiency in the brain. Copper accumulation in brain endothelial cells increases the rate of FWH reaction and prevents the transport of essential metal ions into the brain cells (astrocytes and neurons) as observed in Menkes’ disease [35]. Although accumulation of iron in livers [36] and copper in kidneys/heart [37] has been reported in rats fed chronic alcohol diets, changes in metal ion concentrations in alcoholic brains are currently unknown. Here, we hypothesize that metabolism of EtOH by ADH and CYP2E1 generates
