Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior-474 002, India.
J Neurol Sci. 2009 Oct 15;285(1-2):198-205. doi: 10.1016/j.jns.2009.07.001. Epub 2009 Jul 26.
We studied the effects of combined exposure to arsenic and fluoride on (i) brain biogenic amines, oxidative stress and its correlation with glutathione and linked enzymes; (ii) alterations in the structural integrity of DNA; and (iii) brain and blood arsenic and fluoride levels. Efficacy of alpha-tocopherol in reducing these changes was also determined. Male mice were exposed to sodium meta arsenite (50 ppm) and sodium fluoride (50 ppm) individually and in combination for ten weeks. Animals were given vitamin E supplementation (5 mg/kg, i.m., alternate days) throughout the experiment. Exposure to arsenic and fluoride significantly decreased the levels of brain biogenic amines. However; acetyl cholinesterase (AChE) and monoamine oxidase (MAO) activities showed an increase on fluoride exposure. There was also an increase in reactive oxygen species, thiobarbituric acid reactive species level, glutathione S-transferase and glutathione peroxidase activities and decreased superoxide dismutase activity, GSH:GSSG ratio, glucose 6-phosphate dehydrogenase activity. Combined exposure to these toxicants produced more pronounced effects on AChE, MAO, SOD and catalase activities. Infrared spectra showed less toxicity during combined exposure as the characteristic peaks of cytosine and alpha-helical structure of DNA were observed in normal and arsenic plus fluoride-exposed animals. Vitamin E reduced brain fluoride level and tissue oxidative stress but had no effect on arsenic. Combined exposure to arsenic and fluoride does not necessarily lead to more pronounced toxicity and interestingly exhibit some antagonistic effects. Vitamin E supplementation may be of added value in reverting some of the toxic effects.
(i)脑生物胺、氧化应激及其与谷胱甘肽和相关酶的关系;(ii)DNA 结构完整性的改变;(iii)脑和血液中的砷和氟水平。还确定了α-生育酚减少这些变化的功效。雄性小鼠分别和联合暴露于亚砷酸钠(50ppm)和氟化钠(50ppm)10 周。整个实验过程中,动物每天接受维生素 E 补充(5mg/kg,肌肉注射,隔日一次)。砷和氟暴露显著降低了脑生物胺的水平。然而,乙酰胆碱酯酶(AChE)和单胺氧化酶(MAO)的活性在氟暴露时增加。活性氧、硫代巴比妥酸反应性物质水平、谷胱甘肽 S-转移酶和谷胱甘肽过氧化物酶活性增加,超氧化物歧化酶活性、GSH:GSSG 比值、葡萄糖 6-磷酸脱氢酶活性降低。这些毒物联合暴露产生了更明显的 AChE、MAO、SOD 和过氧化氢酶活性的影响。红外光谱显示联合暴露时的毒性较小,因为在正常和砷加氟暴露的动物中观察到了胞嘧啶和 DNAα-螺旋结构的特征峰。维生素 E 降低了脑氟水平和组织氧化应激,但对砷没有影响。砷和氟的联合暴露不一定会导致更明显的毒性,而且有趣的是表现出一些拮抗作用。维生素 E 补充可能对逆转一些毒性作用具有附加价值。