THERAPEUTIC SUBSTANCES

Ethanol induces oxidative stress and its exposure during early developmental age causes neuronal cell death which leads to several neurological disorders. We previously reported that vitamin C can protect against ethanol-induced apoptotic cell death in developing rat brain. Here, we extended our study to know the therapeutic efficacy of vitamin C against ethanol-induced oxidative stress, neuroinflammation mediated neurodegeneration in postnatal day 7 (PND7) rats. A single episode of ethanol (5g/kg) subcutaneous administration to PND7 rats significantly induced the production of reactive oxygen species (ROS), activation of both microglia and astrocytes followed by the induction of different apoptotic markers. On the other hand due to its free radical scavenging properties vitamin C treatment significantly reduced ROS production, suppressed both activated microglia and astrocytes and reversed other changes including elevated level of Bax/Bcl-2 ratio, cytochrome c and different caspases such as caspase-9 and caspase-3 induced by ethanol in developing rat brain. Moreover, vitamin C treatment also reduced ethanol-induced activation of PARP-1 and neurodegeneration as evident from Flouro-Jade-B and Nissl stainined neuronal cell death in PND7 rat brain. These findings suggest that vitamin C mitigated ethanol-induced oxidative stress, neuroinflammation and apoptotic neuronal loss and may be beneficial against ethanol abusing in brain development.