Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-54766
Nishina, A; Kimura, H; Kozawa, K; Sommen, G; Favero, F; Heimgartner, H; Koketsu, M; Furukawa, S (2011). 3-(2,6-Dimethylphenyl)-2-selenoxo-1,3-thiazolidin-4-one suppresses hydrogen peroxide-induced cytotoxicity on PC12 cells via activation of MAPK. International Journal of Toxicology, 30(6):690-699.
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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 (O2 −)-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 O2 −-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 O2 −-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 (IC50) 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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||07 Faculty of Science > Institute of Organic Chemistry|
|Deposited On:||09 Jan 2012 14:29|
|Last Modified:||20 May 2013 17:42|
|Additional Information:||The final, definitive version is available at http://online.sagepub.com/.|
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