权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Mechanism of diphenylarsinic acid intoxication and the treatment method

二苯胂酸中毒的机制及治疗方法

基本信息

批准号：
16209021
负责人：
ENDO Ginji
金额：
$ 27.71万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

1. We noted a new clinical syndrome with prominent cerebellar-brainstem symptoms such as ataxic gait, titubation and scanning speech, myoclonus and tremor, and cerebral symptoms such as upward gaze-evoked nystagmus, sleep disorder, and memory impairment in residents who had drunk well water contaminated by diphenylarsinic acid (DPAA). Mental retardation associated with brain atrophy in magnetic resonance images was evident in some infants.2. Motor impairment and the down -regulation of the dopamine receptor function in striatum were observed in adult mice treated with DPAA. Motor learning impairment was observed in neonatal mice exposed to a low dose of DPAA.3. Administration of 20 ppm DPAA for 6 weeks significantly increased the number and areas of glutathione S-transferase placental form positive foci induced by diethylnitrosamine in rats. These results indicated the DPAA exerts promoting hepatocarinogenesis in rats.4. Pathogenetic observations of DPAA intoxication were the vacuolation of glomerulus in granular layer of cerebellum by microscope, and the axonal degeneration by electron microscope.5. Significantly positive staining with malondialdehyde and 3-nitrotyrosine was observed in the cerebellar Purkinje cells by repeated administration (5 mg/kg/day) with DPA for 5 weeks that led to the cerebellar symptoms from a behavioral pharmacology standpoint. These results suggest that DPAA associated novel active species may be a factor underlying the oxidative and nitrosative stress in Purkinje cells, and the damage lead to the cerebellar symptpms.6. A selective and efficient clean-up method with solvent extraction and solid phase extraction for DPAA in fat and brain was developed.7. We measured urinary arsenic compounds in 142 workers by HPLC-ICP-MS. DPAA peaks were detected in none of the workers.

1.在饮用了受DPAA污染的井水的居民中，我们发现了一种新的临床症状，具有明显的小脑-脑干症状，如共济失调步态、姿势和扫视语言、肌阵挛和震颤，以及脑症状如向上凝视诱发的眼球震颤、睡眠障碍和记忆障碍。结论：1.在一些婴儿中，与脑萎缩相关的智力低下在磁共振成像中是明显的。在DPAA处理的成年小鼠中观察到运动障碍和纹状体多巴胺受体功能的下调。在小剂量DPAA暴露的新生小鼠中观察到运动学习障碍。给药6周，20ppmDPAA可显著增加二乙基亚硝胺所致大鼠胎盘型谷胱甘肽S转移酶阳性灶的数目和面积。这些结果表明，DPAA具有促进大鼠肝细胞癌发生的作用。光镜下可见小脑颗粒层肾小球空泡化，电子显微镜下可见轴突变性。重复给予DPA(5 mg/kg/d)5周后，小脑浦肯野细胞内丙二醛和3-硝基酪氨酸呈明显阳性染色，从行为药理学角度来看，可导致小脑症状。这些结果表明，DPAA相关的新活性物种可能是浦肯野细胞氧化和亚硝化应激的一个因素，这种损伤导致小脑症状PM。建立了一种选择性、高效的溶剂萃取和固相萃取相结合的脂肪和脑中DPAA的净化方法。采用高效液相色谱-电感耦合等离子体质谱联用技术对142名作业工人的尿砷化合物进行了测定。在所有工人身上均未检测到DPAA峰。