Wang R S, Nakajima T, Honma T
Division of Health Effects Research, National Institute of Industrial Health, Kawasaki, Japan.
Toxicology. 1999 Jan 1;132(1):9-18. doi: 10.1016/s0300-483x(98)00132-2.
The effects of trichloroethylene (TCE) administration on aldehyde dehydrogenase (ALDH) and cytochrome P450 isozymes were studied in rats and compared with those of methanol. Intragastric administration of TCE to rats at 0.05 or 0.2 ml/kg for 1 week significantly inhibited ALDH activity for aliphatic aldehydes of short chains in the mitochondrial and cytosolic fractions of rat liver, respectively, but had no effect on the activity for long chain aliphatic aldehydes. ALDH activity catalyzing the metabolism of some aromatic aldehydes was even induced by TCE. Microsomal ALDH activity was not decreased by TCE treatment. A kinetic study showed that the low-Km isozyme of ALDH for propionaldehyde in mitochondrial and cytosolic fractions was inhibited by TCE treatment. Addition of TCE, trichloroethanol or trichloroacetic acid to the in vitro assay system did not affect the activity for acetaldehyde, but chloral hydrate at 0.02 mM decreased the activity by 42 and 35% in cytosol and the 700 x g supernatant, respectively. Methanol treatment, on the other hand, had no effect on any ALDH activity. Both TCE and methanol significantly induced CYP2E1 in rat liver. The combined effects of TCE on ALDH and cytochrome P450 may account for the degreasers' flush. Exposure to TCE and methanol may result in a change in the metabolism and toxicity of other chemicals.
研究了三氯乙烯（TCE）给药对大鼠醛脱氢酶（ALDH）和细胞色素P450同工酶的影响，并与甲醇的影响进行了比较。以0.05或0.2 ml/kg的剂量给大鼠灌胃TCE 1周，分别显著抑制了大鼠肝脏线粒体和胞质部分中短链脂肪醛的ALDH活性，但对长链脂肪醛的活性没有影响。TCE甚至诱导了催化某些芳香醛代谢的ALDH活性。TCE处理并未降低微粒体ALDH活性。动力学研究表明，TCE处理抑制了线粒体和胞质部分中丙醛的低Km ALDH同工酶。在体外测定系统中添加TCE、三氯乙醇或三氯乙酸不影响乙醛的活性，但0.02 mM的水合氯醛使胞质和700 x g上清液中的活性分别降低了42%和35%。另一方面，甲醇处理对任何ALDH活性均无影响。TCE和甲醇均显著诱导大鼠肝脏中的CYP2E1。TCE对ALDH和细胞色素P450的联合作用可能解释了脱脂剂潮红现象。接触TCE和甲醇可能导致其他化学物质的代谢和毒性发生变化。
