Abe K, Saito H
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Pharmacol Toxicol. 1998 Jul;83(1):40-6. doi: 10.1111/j.1600-0773.1998.tb01440.x.
The present study investigates the toxicity of t-butyl hydroperoxide (t-BuOOH) in cultured rat cortical neurones and astrocytes. Both neurones and astrocytes were destroyed by exposure to t-BuOOH in a time- and concentration-dependent manner. Astrocytes were more resistant to destruction by hydrogen peroxide (H2O2) than neurones, but there was no difference in susceptibility to t-BuOOH between neurones and astrocytes. The toxic effect of t-BuOOH was significantly blocked by antioxidants, propyl gallate and trolox, but not by superoxide dismutase nor by H2O2-scavengers, catalase and 4-nitrophenylglyoxylic acid. These results suggest that t-BuOOH toxicity is caused by oxidative stress unrelated to superoxide and H2O2. In addition, the toxic effect of t-BuOOH was attenuated by the presence of iron chelators, deferoxamine and N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine, indicating the requirement of endogenous iron for t-BuOOH toxicity.
本研究调查了叔丁基过氧化氢(t-BuOOH)对培养的大鼠皮质神经元和星形胶质细胞的毒性。神经元和星形胶质细胞暴露于t-BuOOH后均会以时间和浓度依赖性方式被破坏。星形胶质细胞比神经元对过氧化氢(H2O2)的破坏更具抗性,但神经元和星形胶质细胞对t-BuOOH的敏感性没有差异。t-BuOOH的毒性作用被抗氧化剂没食子酸丙酯和生育三烯酚显著阻断,但超氧化物歧化酶以及H2O2清除剂过氧化氢酶和4-硝基苯乙酮酸却不能阻断。这些结果表明,t-BuOOH毒性是由与超氧化物和H2O2无关的氧化应激引起的。此外,铁螯合剂去铁胺和N,N,N',N'-四(2-吡啶甲基)乙二胺的存在减弱了t-BuOOH的毒性作用,表明t-BuOOH毒性需要内源性铁。