TY - JOUR
T1 - 3-(2,6-dimethylphenyl)-2-selenoxo-1,3-thiazolidin-4-one suppresses hydrogen peroxide-induced cytotoxicity on PC12 cells via activation of MAPK
AU - Nishina, Atsuyoshi
AU - Kimura, Hirokazu
AU - Kozawa, Kunihisa
AU - Sommen, Geoffroy
AU - Favero, Francesco
AU - Heimgartner, Heinz
AU - Koketsu, Mamoru
AU - Furukawa, Shoei
PY - 2011/12
Y1 - 2011/12
N2 - 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 mmol/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 (IC50) of compound Aa was 25.9 mmol/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.
AB - 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 mmol/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 (IC50) of compound Aa was 25.9 mmol/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.
KW - Animals
KW - Antioxidants/chemical synthesis
KW - Cell Proliferation/drug effects
KW - Cell Survival/drug effects
KW - Hydrogen Peroxide/toxicity
KW - Mitogen-Activated Protein Kinases/metabolism
KW - Organoselenium Compounds/chemical synthesis
KW - PC12 Cells
KW - Rats
KW - Superoxides/metabolism
U2 - 10.1177/1091581811419267
DO - 10.1177/1091581811419267
M3 - Journal article
C2 - 21960664
SN - 1091-5818
VL - 30
SP - 690
EP - 699
JO - International Journal of Toxicology
JF - International Journal of Toxicology
IS - 6
ER -