title: N-Adamantyl-4-Methylthiazol-2-Amine Attenuates Glutamate-Induced Oxidative Stress and Inflammation in the Brain.
abstract: In this study, we explored the possible mechanisms underlying the neuroprotective and anti-oxidative effects of N-adamantyl-4-methylthiazol-2-amine (KHG26693) against in vivo glutamate-induced toxicity in the rat cerebral cortex. Our results showed that pretreatment with KHG26693 significantly attenuated glutamate-induced elevation of lipid peroxidation, tumor necrosis factor-α, interferon gamma, IFN-γ, interleukin-1β, nitric oxide, reactive oxygen species, NADPH oxidase, caspase-3, calpain activity, and Bax. Furthermore, KHG26693 pretreatment attenuated key antioxidant parameters such as levels of superoxide dismutase, catalase, glutathione, and glutathione reductase. KHG26693 also attenuated the protein levels of inducible nitric oxide synthase, neuronal nitric oxide synthase, nuclear factor erythroid 2-related factor 2, heme oxygenase-1, and glutamate cysteine ligase catalytic subunit caused by glutamate toxicity. Finally, KHG26693 mitigated glutamate-induced changes in mitochondrial ATP level and cytochrome oxidase c. Thus, KHG26693 functions as neuroprotective and anti-oxidative agent against glutamate-induced toxicity through its antioxidant and anti-inflammatory activities in rat brain at least in part.
authors.affiliation: Department of Biomedical Laboratory Science, Konyang University, Daejeon, 35365, South Korea.
authors.forename: Seung-Ju
authors.initials: SJ
authors.lastname: Yang
authors.affiliation: Department of Biomedical Laboratory Science, Konyang University, Daejeon, 35365, South Korea.
authors.forename: Eun-A
authors.initials: EA
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, 88, Olympic-ro 43-Gil, Songpa-gu, Seoul, 05505, South Korea.|Sema High School, 559-17, Sumokwon-Ro, Osan-si, Kyeonggi-do, 18107, South Korea.
authors.forename: Min-Jun
authors.initials: MJ
authors.lastname: Chang
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, 88, Olympic-ro 43-Gil, Songpa-gu, Seoul, 05505, South Korea.
authors.forename: Jiae
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, 88, Olympic-ro 43-Gil, Songpa-gu, Seoul, 05505, South Korea.
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Na
authors.affiliation: Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, South Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, 88, Olympic-ro 43-Gil, Songpa-gu, Seoul, 05505, South Korea. swcho@amc.seoul.kr.
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism; D004660:Encephalitis / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018698:Glutamic Acid / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D009281:Naphthalenes / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: C000613502:3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride; D000893:Anti-Inflammatory Agents; D001384:Azetidines; D016207:Cytokines; D018690:Excitatory Amino Acid Agonists; D009281:Naphthalenes; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Glutamate; N-Adamantyl-4-methylthiazol-2-amine; Neuroinflammation; Oxidative stress