Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
Environ Toxicol Pharmacol. 2007 May;23(3):286-96. doi: 10.1016/j.etap.2006.11.004.
Following combustion of fuel containing the additive methylcyclopentadienyl-manganese-tricarbonyl (MMT), manganese phosphate (MnPO(4)) and manganese sulfate (MnSO(4)) are emitted in the atmosphere. Manganese chloride (MnCl(2)), another Mn(2+) species, is widely used experimentally. Using rat striatal slices, we found that MnPO(4) decreased tissue and media dopamine (DA) and media Dopac (a DA metabolite) levels substantially more than either MnCl(2) or MnSO(4); antioxidants were partially protective. Also, both MnCl(2) and MnPO(4) (more potently) oxidized DA and Dopac even in the absence of tissue in the media, suggesting a direct interaction between Mn and DA/Dopac. Because aminochrome is a major oxidation product of DA, we next determined whether MnPO(4) will be more potent in forming aminochrome than MnCl(2) or MnSO(4) which, indeed, was the case. Thus, a potential additional mechanism for the neurotoxic effects of environmentally-relevant forms of Mn, MnPO(4) in particular, is the generation of reactive DA intermediates.
燃烧含有添加剂甲基环戊二烯基三羰基锰(MMT)的燃料后,会在大气中排放出磷酸锰(MnPO4)和硫酸锰(MnSO4)。另一种 Mn2+物质氯化锰(MnCl2)在实验中也被广泛使用。我们使用大鼠纹状体切片发现,磷酸锰(MnPO4)使组织和培养基中的多巴胺(DA)和多巴胺代谢产物(Dopac)水平显著降低,比氯化锰(MnCl2)或硫酸锰(MnSO4)的作用更明显;抗氧化剂则有部分保护作用。此外,MnCl2和 MnPO4(作用更强烈)即使在培养基中没有组织的情况下也能氧化 DA 和 Dopac,这表明 Mn 与 DA/Dopac 之间存在直接相互作用。由于氨基酸铬是 DA 的主要氧化产物,我们接下来确定磷酸锰(MnPO4)是否比氯化锰(MnCl2)或硫酸锰(MnSO4)更能形成氨基酸铬,事实确实如此。因此,环境相关形式的 Mn(特别是 MnPO4)产生神经毒性作用的另一个潜在机制是活性 DA 中间产物的生成。