Arsenic-induced toxicity: effect on protein composition in sciatic nerve

Abstract

<jats:p> 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. </jats:p>

Scientific Opinion on Arsenic in Food

“…injected in a tail vein, Vahidnia et al, 2006) and a 4-12 week repeated daily administration (3, 10 mg/kg b.w., intragastric route, Vahidnia et al, 2008a), whereas in vitro neither arsenite nor arsenate (0.3-3 µM, 24 or 48 hours incubation) changed NF-L gene expression (Vahidnia et al, EFSA Journal 2009;7 (10):1351 2007b). However, in vitro trivalent inorganic arsenic increased intracellular calcium (Florea et al, 2007), which is most probably responsible for p35 proteolytic cleavage to p25 by calpain resulting in hyperphosphorylation of cytoskeletal proteins including MAP-tau (Vahidnia et al, 2008b).…”

Taurine resumed neuronal differentiation in arsenite-treated N2a cells through reducing oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction

“…On the other hand, As-induced degeneration of axon structure may also be the contributor for delaying brain development. Obvious decline of the neurofilament light chain in sciatic nerve is found in As-treated rats, and this contributed to degeneration of the nervous integrity (Vahidnia et al 2006). Besides, As intoxication gave rise to reduction of nerve conduction velocity and might involve axonal degeneration (Goebel et al 1990).…”

Metal toxicity at the synapse: presynaptic, postsynaptic and long-term effects

“…Wistar rats to arsenic caused a dose-dependent decrease in neurofilament M and L proteins in the sciatic nerve [113]. These components are required for the formation of a heteropolymer in the cytoskeleton.…”

“…Neurotransmitter release was possibly affected through interaction with many of the targets above as well as through interaction with synthesis and degradation of neurotransmitters and enzymes in the metabolic pathway, which resulted in modulation of neurotransmitter release by metals such as copper, manganese, and tin [101][102][103]. The mRNA expression of neurofilaments was affected by arsenic [113]. Often contradictory results were obtained regarding the effects of metals, which may indicate that metals had different effects on targets depending on the state of the metal, its concentration, the medium, the area of the brain, and whether the experiment was in vivo or in vitro.…”