title: Anti-oxidative and anti-inflammatory effects of 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride on glutamate-induced neurotoxicity in rat brain.
abstract: In a previous in vitro study, we demonstrated the protective effects of a new drug, 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride (KHG26377), against glutamate-induced excitotoxicity in cultured glial cells. In this study, we explored the possible mechanisms underlying the neuroprotective and anti-inflammatory effects of this compound against glutamate-induced excitotoxicity in rat brain. Our results showed that pretreatment with KHG26377 significantly attenuated glutamate-induced elevation of lipid peroxidation, TNF-α, IFN-γ, nitric oxide, reactive oxygen species, NADPH oxidase, and Ca(2+) levels, as well as the expression of caspase-3, neuronal nitric oxide synthase, and pERK. Furthermore, KHG26377 pretreatment attenuated key antioxidant parameters such as levels of superoxide dismutase, catalase, glutathione, glutathione peroxidase, and glutathione reductase, and also mitigated suppression of mitochondrial transmembrane potential by glutamate toxicity. Thus, through its antioxidant and anti-inflammatory activities in rat brain, KHG26377 may help protect against glutamate-induced neuronal damage.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
authors.forename: Eun-A
authors.initials: EA
authors.lastname: Kim
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Choi
authors.forename: A Reum
authors.initials: AR
authors.lastname: Han
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Hoh-Gyu
authors.initials: HG
authors.lastname: Hahn
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000096:biosynthesis; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018698:Glutamic Acid / Q000633:toxicity*; D007371:Interferon-gamma / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D019255:NADPH Oxidases / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C550808:2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D018698:Glutamic Acid; D007371:Interferon-gamma; D052248:Nitric Oxide Synthase Type I; D019255:NADPH Oxidases; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D002118:Calcium
keywords: 2-Cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride; Calcium; Cytokines; Glutamate; Reactive oxygen species