|show drug details|
|Caswell No. 389C|
|EPA Pesticide Chemical Code 055102|
|WLN: WNR BG ENW|
|Ki: ||Kd:||Ic 50:||Ec50/Ic50:|
Cell death by 1-chloro-2,4-dinitrobenzene, an inhibitor of thioredoxin reductase and its dual regulation by nitric oxide in rats.. A Ishikawa; Y Kubota; T Murayama; Y Nomura (1999) Neuroscience letters display abstract
Thioredoxin (Trx), the oxidized form of which is converted to a reduced form by Trx reductase, regulates cell proliferation and survival. We investigated the effect of 1-chloro-2,4-dinitrobenzene (DNCB), an inhibitor of Trx reductase, on cell death in neuronal PC12 cells and rat glial cells. In both types of cells, culture with DNCB for 4 h stimulated lactate dehydrogenase (LDH) leakage. LDH leakage by DNCB was inhibited by an inhibitor of caspases. Addition of 2,2-(hydroxynitrosohydrazino)bis-ethanamine, of which 50% decays and releases nitric oxide (NO) in 21 h, inhibited DNCB-induced LDH leakage. Addition of 10 microM N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)-ethanamine (NOC-12), of which 50% decays and releases NO in 100 min, inhibited DNCB-induced LDH leakage, although 0.2 mM NOC-12 enhanced the leakage in PC12 cells. These findings suggest that DNCB induces cell death of neuronal and glial cells accompanied by caspase(s) activation. NO inhibits DNCB-induced cell death in both types of cells, although excess NO showed a toxic effect.
Possible involvement of nitric oxide synthase in oxidative stress-induced endothelial cell injury.. M Ishii; T Yamamoto; S Shimizu; A Sano; K Momose; Y Kuroiwa (1997) Pharmacology & toxicology display abstract
The purpose of this study was to characterize the protective effect of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, on oxidative stress-induced endothelial cell injury. Intracellular oxidative stress was induced by 1-chloro-2,4-dinitrobenzene, a glutathione (GSH) depleting agent, and the leakage of intracellular lactate dehydrogenase was measured as a marker of cell injury. Addition of 1-chloro-2,4-dinitrobenzene (100-500 microM) induced leakage of lactate dehydrogenase from endothelial cells, and the leakage of lactate dehydrogenase was strongly attenuated by L-NAME, but not by NG-methyl-L-arginine, also an inhibitor of nitric oxide synthase. However, cell injury induced by the Ca2+ ionophore ionomycin was not affected by L-NAME or NG-methyl-L-arginine. Moreover, neither L-NAME nor NG-methyl-L-arginine affected GSH depleting agent-induced or H2O2-induced cell injury in a rat foetal lung fibroblast cell line which lacks nitric oxide synthase. These results suggest that the protective effect of L-NAME is likely to be related to nitric oxide synthase, while the inhibition of nitric oxide production may not be involved in the protective effect of L-NAME, since NG-methyl-L-arginine did not affect endothelial cell injury.