The effect of diethyldithiocarbamate on the biodisposition of MPTP: an explanation for enhanced neurotoxicity.
The effect of diethyldithiocarbamate on the biodisposition of MPTP: an explanation for enhanced neurotoxicity.
复制标题
二乙基二硫代氨基甲酸酯对 MPTP 生物处置的影响：神经毒性增强的解释。
DOI：
10.1016/0014-2999(87)90265-2
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发表时间：
1987
影响因子：
5
通讯作者：
Langston,JW
中科院分区：
文献类型：
--
作者：
Irwin,I;Wu,EY;DeLanney,LE;Trevor,A;Langston,JW
Diethyldithiocarbamate (DDC) has been reported to exacerbate the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. In this study, the effects of DDC on the biotransformation and distribution of MPTP and 1-methyl-4-phenylpyridinium ion (MPP+, the putative toxic metabolite of MPTP) were investigated. When DDC was administered prior to a standardized dosage of MPTP, the initial concentrations of MPTP in striatum, ventral mesencephalon and frontal cortex were markedly increased when compared to animals given MPTP alone. The pre-administration of DDC also produced increased concentrations of MPP+in these regions at all time points studied. Further, the rate of disappearance of MPP+from brain was significantly less in DDC pretreated animals, when compared to animals given MPTP alone. In vitro studies, using either brain homogenates or partially purified MAO-B, showed that DDC enhanced the biotransformation of MPTP. These results suggest that DDC enhances MPTP-induced neurotoxicity by increasing brain concentrations of MPP+. Factors contributing to this increase appear to include greater delivery of MPTP to the central nervous system (CNS), increased biotransformation of MPTP to MPP+via MAO, and possibly reduced clearance of MPP+from the brain.
