Wilson A, Trombetta L D
College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, NY 11439, USA.
Toxicol Lett. 1999 Mar 29;105(2):129-40. doi: 10.1016/s0378-4274(98)00392-0.
The neurotoxicity of diethyldithiocarbamate (DDC) has been documented for decades. In particular, cytotoxic effects against rat astrocytes have been noted by a decrease in cell viability and numerous ultrastructural defects. This study indicates an in vitro protective effect by zinc administration prior to DDC insult. Cell groups pre-treated with 50 microM ZnCl2 prior to the addition of 35 microg/ml DDC showed significant protection when compared with cells treated with DDC alone. Zinc reduced the DDC-mediated toxicity to astrocytes as indicated by an increase in cell adherence and viability. Morphological evaluation indicated a significant decrease in ultrastructural alterations. Metallothionein (MT), a metal regulatory protein known to be induced by zinc was studied to determine its role in this mechanism of protection. Immunocytochemistry and immunoblots showed increased presence of MT in all zinc treated groups. This suggests a protective effect against DDC cytotoxicity on rat astrocytes in vitro may be associated with an increase in MT concentration.
二乙基二硫代氨基甲酸盐(DDC)的神经毒性已被记录数十年。特别是,已注意到对大鼠星形胶质细胞的细胞毒性作用表现为细胞活力下降和众多超微结构缺陷。本研究表明在DDC损伤之前给予锌具有体外保护作用。与仅用DDC处理的细胞相比,在添加35μg/ml DDC之前用50μM ZnCl2预处理的细胞组显示出显著的保护作用。锌降低了DDC介导的对星形胶质细胞的毒性,表现为细胞黏附性和活力增加。形态学评估表明超微结构改变显著减少。研究了金属硫蛋白(MT),一种已知可由锌诱导的金属调节蛋白,以确定其在这种保护机制中的作用。免疫细胞化学和免疫印迹显示所有锌处理组中MT的存在增加。这表明对体外大鼠星形胶质细胞DDC细胞毒性的保护作用可能与MT浓度增加有关。