title: 3-(2,6-dimethylphenyl)-2-selenoxo-1,3-thiazolidin-4-one suppresses hydrogen peroxide-induced cytotoxicity on PC12 cells via activation of MAPK.
abstract: We newly synthesized organic selenium compounds (5-membered ring compounds) including 2-selenoxo-1,3-thiazolidin-4-ones (compounds A) and 3-alkoxy-4,5-dihydro-5-selenoxo-1H-1,2,4-triazole-1-carboxylates (compounds B). To address whether these compounds show antioxidative effects, we also examined their superoxide radical (O(2)               (-))-scavenging effects. Moreover, we examined the effects of compound Aa on the activation of mitogen-activated protein kinase/extracellular signal-regulated protein kinases (MAPK/ERK1/2) and suppression of hydrogen peroxide-induced cytotoxicity in rat pheochromocytoma cells (PC12 cells). We evaluated the O(2)               (-)-scavenging activities of the compounds by a chemiluminescence method, and activation of ERK1/2 in PC12 cells was evaluated by Western blot analysis. At 166 μmol/L, the O(2)               (-)-scavenging activities were markedly different among compounds A and B. 3-(2,6-Dimethylphenyl)-2-selenoxo-1,3-thiazolidin-4-one (compound Aa) exhibited the strongest superoxide anion-scavenging activity among compounds A and B. The concentration necessary for 50% inhibition of the activity (IC(50)) of compound Aa was 25.9 μmol/L. Compound Aa activated ERK1/2 of the PC12 cell, as did ebselen, and suppressed hydrogen peroxide-induced cytotoxicity more potently than ebselen. In addition, the toxicity of compound Aa was less than that of ebselen. From these results, it is assumed that compound Aa is a candidate drug to prevent oxidative stress-induced cell death.
authors.affiliation: Division of Health and Nutrition, Yonezawa Women’s Junior College,Yonezawa, Yamagata, Japan. nishina@yone.ac.jp
authors.forename: Atsuyoshi
authors.initials: A
authors.lastname: Nishina
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kimura
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Kozawa
authors.forename: Geoffroy
authors.initials: G
authors.lastname: Sommen
authors.forename: Francesco
authors.initials: F
authors.lastname: Favero
authors.forename: Heinz
authors.initials: H
authors.lastname: Heimgartner
authors.forename: Mamoru
authors.initials: M
authors.lastname: Koketsu
authors.forename: Shoei
authors.initials: S
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D013481:Superoxides / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016566:Organoselenium Compounds; D013481:Superoxides; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases