Glycine inhibits ethanol-induced oxidative stress, neuroinflammation and apoptotic neurodegeneration in postnatal rat brain.
Here we investigated for the first time the inhibitory potential of Glycine (Gly) against ethanol-induced oxidative stress, neuroinflammation and apoptotic neurodegeneration in human neuroblastoma SH-SY5Y cells and in the developing rat brain. The Gly co-treatment significantly increased the cell viability, inhibited the expression of phospho-Nuclear Factor kappa B (p-NF-kB) and caspase-3 and reduced the oxidative stress in ethanol-treated SH-SY5Y cells in a PI3K-dependent manner. Seven days old male rat pups were injected with ethanol (5 g/kg subcutaneously, prepared in a 20% saline solution) and Gly (1 g/kg). Gly co-treatment stimulated the PI3K/Akt signaling pathway to limit the ethanol induced reactive oxygen species (ROS) production in the developing rat brain. It lowered the ethanol-elevated levels of phospho-c Jun N terminal kinase (p-JNK) and its various downstream apoptotic markers, including Bax, cytochrome C, caspase-3 and PARP-1. Additionally, the Gly treatment upregulated antiapoptotic Bcl-2 proteins and prevented ethanol-induced neurodegeneration as assessed by Fluoro-Jade-B (FJB) and Nissl staining. Furthermore, the Gly administration caused significant reduction in the ethanol-induced neuroinflammation by inhibiting the expression of inflammatory markers such as p-NF-kB, cyclooxygenase 2 (COX2) and tumor necrosis factor-α (TNF-α) and reversed the ethanol-induced synaptic protein markers expression. The results suggest that acute Gly treatment reduces ethanol-induced oxidative stress and neuronal cell loss in SH-SY5Y cells and in the developing rat brain. Therefore, Gly may be considered as potential treatment in ethanol-intoxicated newborns and infants.
['Amin|Faiz Ul|FU|', 'Shah|Shahid Ali|SA|', 'Kim|Myeong Ok|MO|']
D000818:Animals D000831:Animals, Newborn D017209:Apoptosis D001921:Brain D045744:Cell Line, Tumor D004305:Dose-Response Relationship, Drug D000431:Ethanol D005998:Glycine D006801:Humans D007249:Inflammation D008297:Male D009410:Nerve Degeneration D018696:Neuroprotective Agents D018384:Oxidative Stress D051381:Rats D017207:Rats, Sprague-Dawley
Glycine Apoptotic neurodegeneration Ethanol FAS Neuroprotection