Kung M P, Nickerson P A, Sansone F M, Olson J R, Kostyniak P J, Adolf M A, Roth J A
Department of Pharmacology and Therapeutics, State University of New York, School of Medicine and Biomedical Sciences, Buffalo 14214.
Neurotoxicology. 1989 Summer;10(2):201-10.
The neurotoxicity associated with chronic exposure to hexachlorophene (HCP) was evaluated by measuring the activity of seven cell specific marker enzymes in brain and by comparing these measurements to morphological changes analyzed by light microscopy. Animals were divided into two groups, the experimental group received HCP at a daily dose of 20 mg/kg p.o. for 53 consecutive days whereas the control group received an equivalent amount of the vehicle only. HCP produced no change in the rate of gain in body weight nor did it produce a statistically significant change in brain weight. Furthermore, no overt abnormal neurological symptoms were observed at this level of exposure to HCP. The white matter throughout the brain was extensively vacuolated in the HCP-treated rats, imparting a spongiform structure which was absent in the white matter of the control animal brains. The data obtained reveal that chronic HCP treatment produce little change in any of the neuronal marker enzymes with the exception of a significant decrease in tyrosine hydroxylase activity in the striatum. Of the nonneuronal enzymes assayed, a significant increase in non-neuronal enolase, glutamine synthetase, and 2',3'-cyclic nucleotide phosphohydrolase was observed in the sciatic nerve, hippocampus and optic nerve, respectively.
通过测量大脑中七种细胞特异性标记酶的活性,并将这些测量结果与光学显微镜分析的形态学变化进行比较,评估了长期接触六氯酚(HCP)的神经毒性。将动物分为两组,实验组连续53天每天口服20mg/kg的HCP,而对照组仅接受等量的赋形剂。HCP对体重增加率没有影响,对脑重也没有产生统计学上的显著变化。此外,在该HCP暴露水平下未观察到明显的异常神经症状。在接受HCP治疗的大鼠中,整个大脑的白质广泛空泡化,呈现出对照动物脑白质中不存在的海绵状结构。获得的数据表明,长期HCP治疗除了使纹状体中的酪氨酸羟化酶活性显著降低外,对任何神经元标记酶的影响都很小。在所检测的非神经元酶中,分别在坐骨神经、海马和视神经中观察到非神经元烯醇化酶、谷氨酰胺合成酶和2',3'-环核苷酸磷酸二酯酶的显著增加。