Neuroprotection by vitamin C against ethanol -induced neuroinflammation associated neurodegeneration in developing rat brain

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, Myeong O. Kim.

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 15 , Issue 3 , 2016

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.

Keywords: Ethanol, vitamin C, reactive oxygen species, inflammation, neurodegeneration, neuroprotection.

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Article Details

VOLUME: 15
ISSUE: 3
Year: 2016
Page: [360 - 370]
Pages: 11
DOI: 10.2174/1871527315666151110130139
Price: $58

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