Williams K D, Porter W R, Peterson R E
Neurotoxicology. 1982 Dec;3(4):221-31.
Our main objective was to describe the metabolism of dithiobiuret (DTB) in the adult, male rat. Based on the thin-layer chromatographic analysis of urine from animals treated ip with 1 mg/kg of [14C] or [35S] labeled DTB, two pathways for metabolism are proposed. One pathway is reversible and involves the oxidation of DTB to thiuret and the reduction of thiuret back to DTB. The other pathway consists of the desulfuration of DTB to monothiobiuret. The liver appears to desulfurate DTB because DTB-derived [35S] was eliminated from the liver more rapidly (T1/2 = 10 hr) than [14C] (T1/2 = 15 hr). The liver was the only tissue where the elimination kinetics of [35S] and [14C] DTB were different. For all extrahepatic tissues examined and plasma, the elimination of DTB-derived [35S] paralleled that of [14C]. The T1/2 for plasma disappearance of both radiolabeled forms of DTB was approximately 10 hr and the cumulative urinary excretion of DTB-derived [35S] and [14C] was parallel and amounted to about 60% of the dose in 24 hr. DTB-derived radioactivity in urine that co-chromatographed with DTB, monothiobiuret, thiuret and sulfate was quantitated along with that of three uncharacterized metabolites. The presence of these unknown metabolites suggests that DTB metabolism is complex. The present study is the first description of the metabolic fate of DTB in the rat and serves as a starting point for determining whether DTB neurotoxicity is caused by the parent compound or a metabolite.
我们的主要目的是描述二硫代双缩脲（DTB）在成年雄性大鼠体内的代谢情况。基于对腹腔注射1mg/kg [¹⁴C] 或 [³⁵S] 标记的DTB的动物尿液进行的薄层色谱分析，提出了两条代谢途径。一条途径是可逆的，涉及DTB氧化为硫脲以及硫脲还原回DTB。另一条途径是DTB脱硫生成单硫代双缩脲。肝脏似乎是使DTB脱硫的部位，因为DTB衍生的 [³⁵S] 从肝脏中消除的速度（T1/2 = 10小时）比 [¹⁴C]（T1/2 = 15小时）更快。肝脏是唯一一处 [³⁵S] 和 [¹⁴C] DTB消除动力学不同的组织。对于所有检查的肝外组织和血浆，DTB衍生的 [³⁵S] 的消除与 [¹⁴C] 的消除情况相似。两种放射性标记形式的DTB在血浆中消失的T1/2约为10小时，DTB衍生的 [³⁵S] 和 [¹⁴C] 的累积尿排泄量相似，在24小时内约占剂量的60%。与DTB、单硫代双缩脲、硫脲和硫酸盐共色谱的尿中DTB衍生放射性以及三种未鉴定代谢物的放射性均被定量。这些未知代谢物的存在表明DTB的代谢很复杂。本研究首次描述了DTB在大鼠体内的代谢命运，为确定DTB神经毒性是由母体化合物还是代谢物引起提供了一个起点。
