Title:Neuroprotection by vitamin C against ethanol -induced neuroinflammation associated neurodegeneration in developing rat brain
Volume: 15
Issue: 3
Author(s): Ashfaq Ahmad, Shahid A. Shah, Haroon Badshah, Min J. Kim, Tahir Ali, Gwang H. Yoon, Tae H. Kim, Nouman B. Abid, Shafiq Ur Rehman, Sohail Khan and Myeong O. Kim
Affiliation:
Keywords:
Ethanol, vitamin C, reactive oxygen species, inflammation, neurodegeneration, neuroprotection.
Abstract: 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 the developing rat brain. Here, we extended our study to understand the therapeutic efficacy of
vitamin C against ethanol-induced oxidative stress, neuroinflammation mediated neurodegeneration in postnatal day 7
(PND7) rat. A single episode of ethanol (5g/kg) subcutaneous administration to postnatal day 7 rat significantly induced
the production of reactive oxygen species (ROS), and activated 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 the production of reactive oxygen species, 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 Poly [ADP-Ribose] Polymerase 1(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 damaging effects in
brain development.
