Arsenic-induced toxicity: effect on protein composition in sciatic nerve.
Exposure to arsenic compounds may lead to skin and lung cancer and various disorders such as vascular disease and peripheral neuropathy in humans. Peripheral arsenic neurotoxicity has been demonstrated clinically and in electrophysiological studies. Patients intoxicated with arsenic show neurological symptoms in their feet and hands. These patients show significantly lower nerve conduction velocities (NCVs) in their peripheral nerves in comparison with controls. The mechanism of arsenic peripheral nervous system (PNS) toxicity, however, has never been described before. This is the first study to investigate the toxicity of arsenic on the PNS. Male Wistar rats were exposed to arsenite given as a single dose i.v. After sacrifice, sciatic nerves were excised and the protein composition was analysed. Protein analysis of sciatic nerves showed disappearance of neurofilament and fibroblast proteins in rats treated with arsenite doses of 15 and 20 mg/kg in comparison with the control groups. Some fibroblast protein bands had disappeared in the 20-mg/kg dose group. The analysed neurofilament-M and -L proteins decreased dose dependency over time. arsenic affects the composition of proteins in the rat sciatic nerve, especially the neurofilaments. The reduction of signals in Western blot analysis reveals changes in cytoskeletal composition, which may well lead to neurotoxic effects in vivo.
Vahidnia
A
A
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands. a.vahidnia@lumc.nl
Romijn
F
F
Tiller
M
M
van der Voet
G B
GB
de Wolff
F A
FA
D000818:Animals; D001151:Arsenic / Q000493:pharmacokinetics / Q000633:toxicity*; D005347:Fibroblasts / Q000378:metabolism; D008297:Male; D016900:Neurofilament Proteins / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000209:etiology; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects* / Q000378:metabolism
D016900:Neurofilament Proteins; D001151:Arsenic