Snyderwine E G, Hunter A
Drug Metab Dispos. 1987 May-Jun;15(3):289-94.
The metabolism and distribution of 14C- and 35S-CS2 was examined in 1-, 5-, 10-, 20-, 30-, and 40-day-old rats. During a 3-hr period following an ip dose of 14C-CS2, 58-83% of the dose was expired as CS2 and 4-9% was metabolized to expired CO2 depending on age. Thirty- and forty-day-old rats metabolized significantly more CS2 to CO2 and expired significantly less CS2 than 1- through 20-day-old rats. At the end of the measured expiration period, only biotransformation products of CS2, which were in part covalently bound, remained in tissues from rats of all ages. Tissue levels of 35S-CS2-derived radioactivity exceeded levels of 14C-CS2-derived radioactivity indicating that sulfur metabolites free from the carbon atom of CS2 were formed in rats as young as 1 day of age. The 35S-CS2-derived radioactivity per g of tissue and thus 35S covalently bound to tissue protein was significantly higher in 1- through 20-day-old rats than in 30- and 40-day-old rats. Twenty-four hr after dosing, up to 13 times more 35S-labeled metabolites were covalently bound in organs from 1-day-old rats than in similar organs from 40-day-old rats. The results showed that elimination of the biotransformation products of CS2, in particular the covalently binding sulfur metabolites, was prolonged in newborn rats in comparison to 40-day-old rats.
在1日龄、5日龄、10日龄、20日龄、30日龄和40日龄的大鼠中研究了14C-和35S-二硫化碳(CS2)的代谢和分布。腹腔注射14C-CS2后的3小时内,根据年龄不同,58%-83%的剂量以CS2形式呼出,4%-9%代谢为呼出的二氧化碳。30日龄和40日龄的大鼠将更多的CS2代谢为二氧化碳,呼出的CS2比1日龄至20日龄的大鼠显著减少。在测量的呼出期结束时,所有年龄段大鼠的组织中仅残留有部分共价结合的CS2生物转化产物。35S-CS2衍生的放射性组织水平超过了14C-CS2衍生的放射性组织水平,这表明在1日龄的幼鼠中就形成了不含CS2碳原子的硫代谢产物。每克组织中35S-CS2衍生的放射性,即与组织蛋白共价结合的35S,在1日龄至20日龄的大鼠中显著高于30日龄和40日龄的大鼠。给药24小时后,1日龄大鼠器官中共价结合的35S标记代谢产物比40日龄大鼠类似器官中的多13倍。结果表明,与40日龄大鼠相比,新生大鼠中CS2生物转化产物的清除,特别是共价结合的硫代谢产物的清除时间延长。