Mechanism of diphenylarsinic acid intoxication and the treatment method

1. 我们注意到饮用二苯基larsinic酸（DPAA）污染井水的居民出现了一种新的临床综合征，表现为明显的小脑-脑干症状，如步态共济失调、蹒跚和扫描性言语、肌颤和震颤，以及脑部症状，如向上凝视诱发的眼球震颤、睡眠障碍和记忆障碍。在一些婴儿中，核磁共振图像显示智力迟钝与脑萎缩相关。DPAA可引起成年小鼠纹状体运动障碍和多巴胺受体功能下调。暴露于低剂量dpaa - 3的新生小鼠观察到运动学习障碍。二乙基亚硝胺诱导大鼠胎盘谷胱甘肽s转移酶阳性灶的数量和面积显著增加。这些结果表明DPAA对大鼠肝癌发生有促进作用。4 . DPAA中毒的病理观察为显微镜下小脑颗粒层肾小球空泡化，电镜下轴突变性。反复给药（5mg /kg/天）5周后，小脑浦肯野细胞丙二醛和3-硝基酪氨酸染色明显阳性，从行为药理学角度来看，这导致小脑症状。这些结果表明，DPAA相关的新型活性物质可能是浦肯野细胞氧化和亚硝酸盐应激的一个潜在因素，这种损伤导致小脑症状。建立了一种溶剂萃取-固相萃取法对脂肪和脑中的DPAA进行选择性高效净化的方法。我们用HPLC-ICP-MS测定了142名工人尿液中的砷化合物。没有工人检测到DPAA峰值。

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.