Active Oxygen Generation as a Possible Mechanism of Selenium Toxicity

作     者：YOSHIYUKISEKO NOBUMASAIMURA 

作者机构：SchoolofpharmaceuticalSciencesKitasatouniversityShirokaneMinato－ku SchoolofpharmaceuticalSciences 

出 版 物：《Biomedical and Environmental Sciences》 (生物医学与环境科学（英文版）)

年 卷 期：1997年第10卷第2期

页      面：333-339页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100104[医学-病理学与病理生理学] 10[医学] 

主　　题：活性氧 硒 毒性机制 GSH 

摘      要：Selenium plays an important role in scavenging active oxygen (AO) species as an essential constituent of glutathione peroxidase. On the other hand, several reports proposed a possible induction of toxic AO by selenium compounds in vitro. However, some of these experiments including ours, were revealed to conclude on the basis of experimental artifacts, and to have problems in the interpretation of *** or principles so far used for the detection of AO species generated by selenium compound were measurement of chemiluminescence from lucigenin or luminol by AO species,the spectrophotometric analysis of reduction of ferricytochrome c or nitroblue tetrazolium (NBT) by superoxide anion (O2-), electron spin resonance (ESR) spectra using dimethylpyrroline oxide (DMPO) as a spin trapping agent, the deoxyribose decomposition by hydroxyl radical (HO), the salicylate hydroxylation by HO, and the strand breakage of DNA by AO. Many of these methods together with their principles seem to have some defects which prevent clear conclusion as stated below. (i) Lucigenin was found to mediate the formation of O2- in the presence of selenite and reduced glutathione (GSH). Therefore, lucigenin is not a suitable reagent. (ii) Luminol may also mediate O2- generation in the presence of HO. (iii) ferricytochrome c can be reduced to ferrocytochrome c in the mixture of selenite and GSH in the absence of oxygen. Moreover, the spectrophotometric method is interfered by turbidity of elemental selenium formed under some conditions in the reaction mixture containing selenite and GSH. (iv) NBT is also reduced by selenium compounds in the absence of O2.(v) ESR signals of AO species were obtained in the reaction mixture containing selenite and GSH, or in the solution of hydrogen selenide in the presence of O2. However, selenide decomposed spin adduct of DMPO with HO (DMPO-OH). Therefore, the intensity of the signals is not quantitative. (vi) CuZn-SOD is not necessarily a good tool to prov the