title: Glycine inhibits ethanol-induced oxidative stress, neuroinflammation and apoptotic neurodegeneration in postnatal rat brain.
abstract: 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.
authors.affiliation: Division of Life Science (BK 21), College of Natural Sciences (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Faiz Ul
authors.initials: FU
authors.lastname: Amin
authors.affiliation: Division of Life Science (BK 21), College of Natural Sciences (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Shahid Ali
authors.initials: SA
authors.lastname: Shah
authors.affiliation: Division of Life Science (BK 21), College of Natural Sciences (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea. Electronic address: mokim@gnu.ac.kr.
authors.forename: Myeong Ok
authors.initials: MO
authors.lastname: Kim
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005998:Glycine / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018696:Neuroprotective Agents; D000431:Ethanol; D005998:Glycine
keywords: Apoptotic neurodegeneration; Ethanol; FAS; Glycine; Neuroprotection