Beattie P J, Brabec M J
Department of Environmental and Industrial Health, University of Michigan, Ann Arbor 48109-2029.
J Biochem Toxicol. 1986 Sep;1(3):61-70. doi: 10.1002/jbt.2570010307.
Ethylene glycol monomethyl ether (EGME) and ethylene glycol monoethyl ether (EGEE) have recently been shown to be potent reproductive toxicants in laboratory animals. The toxicity of these compounds is believed to be due to their metabolites, methoxyacetic acid (MAA) and ethoxyacetic acid (EAA). Since the primary targets of EGME and EGEE appear to be tissues with rapidly dividing cell systems and high rates of respiration and energy metabolism, the effects of these compounds and their proposed metabolites on mitochondria were investigated. At concentrations beginning at 3.85 mM, MAA and EAA inhibited state 3 respiration and the respiratory control ratio (RCR) in hepatic mitochondria with either succinate or citrate/malate as substrates. Cytochrome c oxidase activity was also inhibited by both metabolites at similar concentrations. The effects of MAA, the metabolite from the more potent compound, on testicular mitochondria were found to be comparable. Neither EGME or EGEE appeared to affect mitochondrial function at concentrations as high as 238 or 113 mM, respectively. These results support the hypothesis that the toxicity of EGME and EGEE are due to their metabolites, MAA and EAA, and that these metabolites may exert their effects, in part, on mitochondrial function.
最近研究表明，乙二醇单甲醚（EGME）和乙二醇单乙醚（EGEE）对实验动物具有很强的生殖毒性。据信这些化合物的毒性是由其代谢产物甲氧基乙酸（MAA）和乙氧基乙酸（EAA）所致。由于EGME和EGEE的主要靶组织似乎是细胞系统快速分裂、呼吸和能量代谢率高的组织，因此研究了这些化合物及其推测的代谢产物对线粒体的影响。以琥珀酸或柠檬酸/苹果酸为底物时，MAA和EAA在浓度低至3.85 mM时就会抑制肝线粒体的状态3呼吸和呼吸控制率（RCR）。两种代谢产物在相似浓度下也会抑制细胞色素c氧化酶活性。发现来自毒性更强的化合物的代谢产物MAA对睾丸线粒体的影响与之相当。EGME和EGEE在浓度分别高达238 mM和113 mM时似乎均不影响线粒体功能。这些结果支持了以下假说：EGME和EGEE的毒性是由其代谢产物MAA和EAA所致，并且这些代谢产物可能部分通过影响线粒体功能发挥作用。
