Huentelman M J, Peters C M, Ervine W E, Polutnik S M, Johnson P
Department of Chemistry and Biochemistry, Ohio University, Athens 45701, USA.
Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1999 Sep;124(1):83-9. doi: 10.1016/s0742-8413(99)00052-3.
In rat thymocytes and cerebellar granule cells, reactive oxygen species (ROS) levels were increased and cell viability was decreased as a result of exposure to ethanol (up to 0.4%). Thymocytes showed larger increases in ROS levels, but neurons showed more pronounced decreases in cell viability. These parameters in neurons were relatively unaffected when the cells were incubated with ethanol in the presence of inhibitors of alcohol-oxidizing enzymes, but in thymocytes, the presence of diallyl sulfide (an inhibitor of alcohol-inducible cytochrome P450, CYP2E1) or 4-methylpyrazole (an inhibitor of CYP2E1 and alcohol dehydrogenase) caused decreases in ROS production from ethanol. In both cell types, the presence of 3-aminotriazole (an inhibitor of catalase) did not decrease ROS production from ethanol. These studies show that the cytotoxic effects of ethanol in neurons may not be the result of oxidative metabolism of ethanol, whereas in thymocytes, the cytotoxic effect of ethanol is principally a result of its oxidative metabolism.
在大鼠胸腺细胞和小脑颗粒细胞中,暴露于乙醇(浓度高达0.4%)会导致活性氧(ROS)水平升高,细胞活力降低。胸腺细胞的ROS水平升高幅度更大,但神经元的细胞活力下降更为明显。当细胞在酒精氧化酶抑制剂存在的情况下与乙醇一起孵育时,神经元中的这些参数相对未受影响,但在胸腺细胞中,二烯丙基硫醚(酒精诱导的细胞色素P450,CYP2E1的抑制剂)或4-甲基吡唑(CYP2E1和乙醇脱氢酶的抑制剂)的存在会导致乙醇产生的ROS减少。在这两种细胞类型中,3-氨基三唑(过氧化氢酶的抑制剂)的存在并未减少乙醇产生的ROS。这些研究表明,乙醇对神经元的细胞毒性作用可能不是乙醇氧化代谢的结果,而在胸腺细胞中,乙醇的细胞毒性作用主要是其氧化代谢的结果。