Oral administration of diphenylarsinic acid, a degradation product of chemical warfare agents, induces oxidative and nitrosative stress in cerebellar Purkinje cells
Oral administration of diphenylarsinic acid, a degradation product of chemical warfare agents, induces oxidative and nitrosative stress in cerebellar Purkinje cells
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DOI：
10.1016/j.lfs.2007.09.030
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发表时间：
2007-11-10
期刊：
影响因子：
6.1
通讯作者：
Yamanaka, Kenzo
中科院分区：
文献类型：
--
作者：
Kato, Koichi;Mizoi, Mutsumi;Yamanaka, Kenzo
本文报道了一种新的临床综合征，患者生活在日本茨木县神栖市，并伴有突出的小脑症状。由于患者摄入了含有二苯胂酸（DPA）的饮用水，DPA是二苯氰胂和二苯氯胂的稳定降解产物，被开发用于化学武器并导致严重的呕吐和打喷嚏，DPA被怀疑是造成临床综合征的原因。本研究的目的是阐明突出的小脑症状，由于DPA。本研究的目的是确定ICR品系小鼠单次（15 mg/kg）或连续（5 mg/kg/天，持续5周）经口给予DPA是否会诱导其大脑中的氧化和/或亚硝化应激。从行为药理学的角度来看，通过DPA重复给药（5 mg/kg/天）5周导致小脑症状，以及通过DPA单次给药（15 mg/kg），在小脑浦肯野细胞中观察到丙二醛（MDA）和3-硝基酪氨酸（3-NT）的显著阳性染色。此外，有可能3-NT的产生不是由过氧亚硝酸盐形成引起的。目前的研究结果表明，砷相关的新的活性物种可能是一个潜在的因素，在浦肯野细胞的氧化和亚硝化应激，由于暴露于DPA，和损害可能导致小脑症状。(C)2007年爱思唯尔公司All rights reserved.
A new clinical syndrome with prominent cerebellar symptoms in patients living in Kamisu City, Ibaraki Prefecture, Japan, is described. Since the patients ingested drinking water containing diphenylarsinic acid (DPA), a stable degradation product of both diphenylcyanoarsine and diphenylchloroarsine, which were developed for use as chemical weapons and cause severe vomiting and sneezing, DPA was suspected of being responsible for the clinical syndrome. The purpose of the present study was to elucidate prominent cerebellar symptoms due to DPA. The aim of the study was to determine if single (15 mg/kg) or continuous (5 mg/kg/day for 5 weeks) oral administration of DPA to ICR-strain mice induced oxidative and/or nitrosative stress in their brain. Significantly positive staining with malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) 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 and by single administration of DPA (15 mg/kg). Furthermore, it is possible that the production of 3-NT was not caused by peroxynitrite formation. The present results suggest the possibility that arsenic-associated novel active species may be a factor underlying the oxidative and nitrosative stress in Purkinje cells due to exposure to DPA, and that the damage may lead to the cerebellar symptoms. (C) 2007 Elsevier Inc. All rights reserved.