Dalvi R R, Deoras D P
Acta Pharmacol Toxicol (Copenh). 1986 Jan;58(1):38-42. doi: 10.1111/j.1600-0773.1986.tb00067.x.
Thiram, tetramethylthiuram disulfide, is used extensively as an agricultural fungicide whose toxicity is largely dependent on its metabolism. The following experiments were carried out to investigate whether carbon disulfide (CS2) is a metabolic product of microsomal monooxygenase catalyzed metabolism of thiram in rats. Adult male Sprague-Dawley rats (160-200 g) were given thiram (60 mg/kg, b.wt.) in corn oil by intraperitoneal injection and placed individually in a metabolic apparatus. Concentration of CS2 in the breath was determined by drawing the expired air through a series of traps containing a CS2 complexing agent. Expiration of CS2 was almost complete within 5 hrs following thiram administration. The formation of CS2 from thiram was increased by pretreatment of rats with phenobarbital and decreased by SKF 525-A. Furthermore, measurement of the activities of hepatic microsomal and serum enzymes at 5 hrs and 24 hrs following thiram treatment indicated that thiram caused significant loss of cytochrome P-450 and benzphetamine N-demethylase activity only at 24 hrs interval whereas there was significant elevation of sorbitol dehydrogenase (SDH) and serum glutamic oxalacetic transaminase (SGOT) activity at 5 and 24 hrs after treatment. The data confirm that CS2 is an in vivo metabolite of thiram and may be, in part, responsible for the observed hepatotoxicity.
福美双，即二硫化四甲基秋兰姆，被广泛用作农业杀菌剂，其毒性很大程度上取决于其代谢过程。进行了以下实验，以研究二硫化碳（CS2）是否是大鼠体内微粒体单加氧酶催化福美双代谢的产物。成年雄性Sprague-Dawley大鼠（体重160 - 200克）通过腹腔注射给予玉米油中的福美双（60毫克/千克，体重），并单独置于代谢装置中。通过使呼出的空气通过一系列含有CS2络合剂的捕集器来测定呼出气体中CS2的浓度。福美双给药后5小时内，CS2的呼出几乎完成。用苯巴比妥预处理大鼠可增加福美双生成CS2的量，而用SKF 525 - A处理则减少。此外，在福美双处理后5小时和24小时测量肝微粒体和血清酶的活性表明，福美双仅在24小时间隔时导致细胞色素P - 450和苄非他明N - 脱甲基酶活性显著丧失，而在处理后5小时和24小时山梨醇脱氢酶（SDH）和血清谷氨酸草酰乙酸转氨酶（SGOT）活性显著升高。数据证实CS2是福美双的体内代谢产物，并且可能部分地导致了所观察到的肝毒性。
