Tsunoda M, Johnson V J, Sharma R P
Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens, Georgia 30602, USA.
Arch Environ Contam Toxicol. 2000 Jul;39(1):32-7. doi: 10.1007/s002440010076.
Selenium (Se) is an essential as well as a toxic trace element. Se intoxication has been reported in both livestock and humans. The central nervous system is sensitive to Se poisoning; exposure to Se causes blind staggers in cattle, poliomyelomalacia in pigs, and nervous system disorders in humans. Differences in neurotoxicity between inorganic and organic Se have been demonstrated. In this study, groups of five male BALB/c mice each were administered sodium selenite or selenomethionine in drinking water ad libitum at 0, 1, 3, and 9 ppm as Se for 14 days. At the end of Se exposure, their brains were removed and dissected into different regions. The concentration of norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindolacetic acid (5-HIAA) were determined in each brain region. Food and water consumption and body weight gain were significantly decreased in the group treated with the highest concentration of sodium selenite. In mice administered sodium selenite at 3 and 9 ppm, DOPAC was significantly higher in the striatum than in the control group. The striatal HVA was also increased in the group treated with 3 ppm Se; the DA showed a similar pattern, but the increase was not statistically significant. No alterations of NE, 5-HT, or 5-HIAA levels were detected in any brain region of mice treated with sodium selenite. No significant differences in any parameter among the groups treated with selenomethionine were observed indicating that inorganic Se was more neurotoxic than organic Se via drinking water. The alterations of DA metabolites by inorganic Se in DA-rich striatum suggested a Se-specific increased neural activity of dopaminergic pathways. Results may be useful in further elucidation of neurotoxicity of Se and in establishing a safe level of intake for this element.
硒（Se）是一种必需的微量元素，同时也是一种有毒的微量元素。家畜和人类中均有硒中毒的报道。中枢神经系统对硒中毒敏感；接触硒会导致牛出现盲目蹒跚、猪出现脊髓软化症以及人类出现神经系统紊乱。无机硒和有机硒在神经毒性方面的差异已得到证实。在本研究中，将每组五只雄性BALB/c小鼠自由饮用含亚硒酸钠或硒代蛋氨酸的水，硒的浓度分别为0、1、3和9 ppm，持续14天。在硒暴露结束时，取出它们的大脑并解剖成不同区域。测定每个脑区中去甲肾上腺素（NE）、多巴胺（DA）、二羟基苯乙酸（DOPAC）、高香草酸（HVA）、5-羟色胺（5-HT）和5-羟吲哚乙酸（5-HIAA）的浓度。最高浓度亚硒酸钠处理组的食物和水消耗量以及体重增加显著降低。在给予3 ppm和9 ppm亚硒酸钠的小鼠中，纹状体中的DOPAC显著高于对照组。在给予3 ppm硒的组中，纹状体HVA也增加；DA呈现类似模式，但增加无统计学意义。在亚硒酸钠处理的小鼠的任何脑区中均未检测到NE、5-HT或5-HIAA水平的改变。在给予硒代蛋氨酸的组中，任何参数均未观察到显著差异，表明通过饮水无机硒比有机硒具有更强的神经毒性。无机硒对富含DA的纹状体中DA代谢产物的改变表明，硒特异性地增加了多巴胺能通路的神经活性。这些结果可能有助于进一步阐明硒的神经毒性，并确定该元素的安全摄入量。
