Nebbia C, Dacasto M, Soffietti M G, Rasero R, Principato G B, Di Simplicio P
Department of Animal Pathology, University of Torino, Italy.
Pharmacol Toxicol. 1993 Oct;73(4):233-9. doi: 10.1111/j.1600-0773.1993.tb01570.x.
Effects of either a single (300 mg/kg) or a subchronic (0.3 and 0.6% for 70 days) oral administration of a dithiocarbamate fungicide (zinc ethylene-bis-dithiocarbamate, zineb) on hepatic drug metabolism and on the activity of several glutathione-dependent enzymes were investigated in male New Zealand White rabbits. While a pronounced reduction in the rate of oxidative biotransformations occurred after either single or repeated exposure, both cytochrome P450 and total haem content were lowered following acute challenge to zineb. None of the experimental protocols affected microsomal carboxylesterase but induced a marked increase in glutathione content and none of the examined glutathione-dependent enzymes was altered by the single administration of zineb, whereas the subchronically exposed rabbits showed a fall in the activities of both total glutathione S-transferase and selenium-independent glutathione peroxidase. In the 0.6% treated animals, a decrease in class mu glutathione S-transferase and glyoxalase I, and an increase in thiol-transferase activities were also recorded. It is concluded that (1) zineb is able to selectively impair oxidative drug metabolism with possible different mechanism(s) according to the duration of the exposure, (2) only the subchronic treatment affects glutathione-dependent enzymes, (3) the decrease in glutathione S-transferase activity would seem to be ascribed to a direct interaction with the fungicide.
研究了在雄性新西兰白兔中，单次口服（300毫克/千克）或亚慢性口服（0.3%和0.6%，持续70天）二硫代氨基甲酸盐类杀菌剂（代森锌）对肝脏药物代谢以及几种谷胱甘肽依赖性酶活性的影响。单次或重复暴露后，氧化生物转化速率均显著降低，急性接触代森锌后，细胞色素P450和总血红素含量均降低。所有实验方案均未影响微粒体羧酸酯酶，但谷胱甘肽含量显著增加，单次给予代森锌未改变所检测的任何谷胱甘肽依赖性酶，而亚慢性暴露的兔子总谷胱甘肽S-转移酶和非硒依赖性谷胱甘肽过氧化物酶的活性均下降。在0.6%处理的动物中，还记录到μ类谷胱甘肽S-转移酶和乙二醛酶I活性降低，硫醇转移酶活性增加。结论如下：（1）代森锌能够根据暴露持续时间，通过可能不同的机制选择性损害氧化药物代谢；（2）只有亚慢性处理会影响谷胱甘肽依赖性酶；（3）谷胱甘肽S-转移酶活性的降低似乎归因于与杀菌剂的直接相互作用。
