Health & Environmental Research Online (HERO)


Print Feedback Export to File
1356872 
Journal Article 
Abstract 
Mechanism of arsenic peripheral neurotoxicity 
Vahidnia, A; Vandervoet, GB; de Wolff, FA 
2005 
1 
Toxicological Sciences
ISSN: 1096-6080
EISSN: 1096-0929 
84 
1-S 
130 
English 
Introduction:Peripheral arsenic neurotoxicity has been demonstrated clinically and in electrophysiological studies. The aim of this study is to investigate the mechanism of the peripheral neurotoxicity of As in rats, with special focus on interactions with axonal cytoskeletal proteins. Methods:Male Wistar rats (225-250g) were exposed to arsenite (NaAsO3) given as a single dose iv (0; 15 or 20 mg/kg) for 3, 6 or 9 hrs. Urine samples were collected for the duration of exposure namely 3, 6 or 9 hrs, whereafter the rats were sacrificed. Sciatic nerves (N. ischiadicus) were excised and cytoskeletal proteins were analysed with SDS-PAGE and Western blot. Arsenic in urine, blood and sciatic nerve was measured with AAS. Results: The amount of arsenic in urine of 15-mg/kg groups decreased in the 9-hour time course from 0.5 to 0.25 (mM As/mM creatinine). Blood arsenic content diminished from 2.3 to 1.58 mg/l in rats group receiving 15 mg/kg doses and reduction of 2.9 to 2.34 mg/l in rats group receiving 20 mg/kg doses. Arsenic was present in sciatic nerve but did not correlate with doses and/or duration of exposure. Biochemical analysis of N. ischiadicus revealed disappearance of neurofilament protein bands and fibroblasts in rats treated with the arsenite doses of 15 and 20 mg/kg. Few fibroblast protein bands disappeared in 20-mg/kg doses analyzed by SDS-PAGE. Some neurofilament proteins diminished in dose/effect manner measured in time and analyzed with western blot. Discussion: Arsenic affects the composition of cytoskeletal proteins in the rat sciatic nerve, especially the neurofilaments. The loss of these neurofilaments could explain the neurotoxicological effects. 
SOT 2005: 44th Annual Meeting & ToxExpo 
New Orleans, LA 
March 6-10, 2005