Leyck S, Freundt K J
J Toxicol Environ Health. 1981 Mar-Apr;7(3-4):533-45. doi: 10.1080/15287398109529999.
In rats, a single oral dose of 30 mg or 1 g thiram per kilogram produced a significant prolongation of the hexobarbital sleeping time or zoxazolamine paralysis time, respectively, a depression of hepatic microsomal O-demethylation of p-nitroanisole to p-nitrophenol, and a decrease in the microsomal cytochrome P-450 content. In addition, incorporation of 14C activity from glucose, glycerol, and palmitic acid into phospholipids (PLs) decreased in most of the components, showing a compensatory increase in only a few of them. Fatty acid (FA) concentrations in phosphatidylcholine (PC) or phosphatidylethanolamine (PE) molecules were increased or decreased from one FA class to the other. This alteration of the FA concentrations in PC and PE, respectively, was virtually exclusively in position 2 of the two PL molecules. The total content of saturated FAs in PC and PE was significantly decreased only after 1 g/kg thiram; this was associated with an increase in total unsaturated FAs. The multiple changes in the bioformation and composition of microsomal membrane PLs suggest a disturbance of the monooxygenase system. It is conceivable that there is an interrelationship between the observed impairment and the inhibitory effect of thiram on the microsomal monoxygenases (MMs).
在大鼠中,每千克体重单次口服30毫克或1克福美双,分别显著延长了己巴比妥睡眠时间或唑沙宗麻痹时间,抑制了肝微粒体将对硝基苯甲醚O - 去甲基化为对硝基苯酚的反应,并降低了微粒体细胞色素P - 450含量。此外,葡萄糖、甘油和棕榈酸中14C活性掺入磷脂(PLs)的情况在大多数组分中减少,仅在少数组分中出现代偿性增加。磷脂酰胆碱(PC)或磷脂酰乙醇胺(PE)分子中的脂肪酸(FA)浓度在不同FA类别之间有增有减。PC和PE中FA浓度的这种变化实际上仅分别发生在这两种PL分子的2位。仅在给予1克/千克福美双后,PC和PE中饱和FA的总含量才显著降低;这与总不饱和FA的增加相关。微粒体膜PLs的生物合成和组成的多种变化表明单加氧酶系统受到干扰。可以设想,观察到的损伤与福美双对微粒体单加氧酶(MMs)的抑制作用之间存在相互关系。