ETHANOL‐INDUCED SUPEROXIDE RADICALS IN FETAL CORTICAL NEURONS: CELLULAR ROS NETWORK

摘要: Alcohol exposure to the developing brain compromises both neurons and glial functions. While are considered primary targets, microglia may play a neurotoxic role in this process. Previous studies demonstrated that neuron death is due oxidative stress mitochondrially mediated (Intrinsic). These showed rapid increase (within minutes) reactive oxygen species (ROS). Due diffusive nature of ethanol multiple sources free radicals, we sought determine source superoxide targeted by ethanol. Confocal suggest radicals originate from mitochondria. Using whole luminol-based chemiluminescence assay (Diogenes) detected extracellular mileu. We observed two-three fold transient steady state generation between 20 minutes one hour (4mg/ml). However, presence Rotenone (mitochondrial complex I inhibitor) DPI (an inhibitor all flavinoids) blocked release these radicals. Interestingly, cortical treated identically with ethanol, greater than five maximum at hour. Moreover, since known induce hydrogen peroxide generation, it was used as mimetic. Hydrogen also induced production different time kinetics. Thus, together data demonstrate induces mileu mitochondrial dependent manner. Since NOX2 an NADPH oxidase expressed neurons, potential candidate for secondary sites generation. The ROS network mitochondria plasma membrane highlights new therapeutical targets counter toxicity.