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

Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands; Department of Clinical Pharmacy and Toxicology, L1-p, Albinusdreef 2, P.O. Box 9600, 2300 RC Leiden, The Netherlands; a.vahidnia{at}lumc.nl

F Romijn

Department of Clinical Chemistry, Leiden University Medical Center, Leiden, The Netherlands

M Tiller

G B van der Voet

F A de Wolff

Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands

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.

Key Words: arsenic • arsenite • fibroblast • nervus ischiadicus • neurofilament • neurotoxicity

References

• Rahman MM, Chowdhury UK, Mukherjee SC, Mondal BK, Paul K, Lodh D et al. Chronic arsenic toxicity in Bangladesh and West Bengal, India–a review and commentary . J Toxicol Clin Toxicol 2001; 39: 683–700 .[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Lagerkvist BJ, Zetterlund B. Assessment of exposure to arsenic among smelter workers: a five-year follow-up . Am J Ind Med 1994; 25: 477–488 .[Web of Science][Medline] [Order article via Infotrieve]
• Hafeman DM, Ahsan H, Louis ED, Siddique AB, Slavkovich V, Cheng Z et al. Association between arsenic exposure and a measure of subclinical sensory neuropathy in Bangladesh . J Occup Environ Med 2005; 47: 778–784 .[Web of Science][Medline] [Order article via Infotrieve]
• Buchanan RJM, Lond MRCD. Cases of arsenical peripheral neuritis. Lancet 1901: 170–172.
• Kelynack TNV, Lond MRCD. Arsenical poisoning from beer drinking. Lancet 1900: 1600–1603.
• Reynolds ES, Lond MRCD. An account of the epidemic outbreak of arsenicals poisoning occurring in beer drinkers in the north of England and the midland counties in 1900. Lancet 1901: 166–170.
• Rowland IR, Davies MJ. Reduction and methylation of sodium arsenate in the rat . J Appl Toxicol 1982; 2: 294–299 .[CrossRef][Medline] [Order article via Infotrieve]
• De Wolff FA, Edelbroek PM. Neurotoxicity of arsenic and its compounds. In Vinken PJ, Bruyn GW eds. Handbook of clinical neurology. Elsevier Science B.V., 1994: 283–291.
• Aposhian HV. Enzymatic methylation of arsenic species and other new approaches to arsenic toxicity . Annu Rev Pharmacol Toxicol 1997; 37: 397–419 .[Medline] [Order article via Infotrieve]
• Otha M. Ultrasrtucture of sural nerve in a case of arsenical neuropathy . Acta Neuropathol 1970; 16: 233–242 .[CrossRef][Medline] [Order article via Infotrieve]
• Soignet SL, Frankel SR, Douer D, Tallman MS, Kantarjian H, Calleja E et al. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia . J Clin Oncol 2001; 19: 3852–3860 .[Abstract/Free Full Text]
• Yip SF, Yeung YM, Tsui EY. Severe neurotoxicity following arsenic therapy for acute promyelocytic leukemia: potentiation by thiamine deficiency . Blood 2002; 99: 3481–3482 .[Free Full Text]
• De Wolff FA, Treijtel N, Vermeulen M. Mechanism of peripheral neurotoxicity. In Lester DS, Slikker W, Lazarovici P eds. Site-selective neurotoxicity. Taylor & Francis, 2002: 282–303.
• Kishi Y, Sasaki H, Yamasaki H, Ogawa K, Nishi M, Nanjo K. An epidemic of arsenic neuropathy from a spiked curry . Neurology 2001; 56: 1417–1418 .[Free Full Text]
• Duenas-Laita A, Perez-Miranda M, Gonzalez-Lopez MA, Martin-Escudero JC, Ruiz-Mambrilla M, Blanco-Varela J. Acute arsenic poisoning . Lancet 2005; 365: 1982–1982 .[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Jha S, Dhanuka AK, Singh MN. Arsenic poisoning in a family . Neurol India 2002; 50: 364–365 .[Web of Science][Medline] [Order article via Infotrieve]
• Le Quesne PM, McLeod JG. Peripheral neuropathy following a single exposure to arsenic. Clinical course in four patients with electrophysiological and histological studies . J Neurol Sci 1977; 32: 437–451 .[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Shen Y, Shen ZX, Yan H, Chen J, Zeng XY, Li JM et al. Studies on the clinical efficacy and pharmacokinetics of low-dose arsenic trioxide in the treatment of relapsed acute promyelocytic leukemia: a comparison with conventional dosage . Leukemia 2001; 15: 735–741 .[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Oudega M, Voormolen JH, Usunoff KG, Marani E, Thomeer RT. Immunocytochemical localization of neurofilaments in the fibre systems of the developing rat spinal cord white matter . Eur J Morphol 1996; 34: 329–346 .[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Buchet JP, Lauwerys R, Roels H. Comparison of several methods for the determination of arsenic compounds in water and in urine. Their application for the study of arsenic metabolism and for the monitoring of workers exposed to arsenic . Int Arch Occup Environ Health 1980; 46: 11–29 .[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4 . Nature 1970; 227: 680–685 .[CrossRef][Medline] [Order article via Infotrieve]
• Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications . Proc Natl Acad Sci U S A 1979; 76: 4350–4354 .[Abstract/Free Full Text]
• Vroemen M, Weidner N. Purification of Schwann cells by selection of p75 low affinity nerve growth factor receptor expressing cells from adult peripheral nerve . J Neurosci Methods 2003; 124: 135–143 .[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Al Chalabi A, Miller CC. Neurofilaments and neurological disease . Bioessays 2003; 25: 346–355 .[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Van Ginkel MF, Heijink E, Dekker PB, Miralem T, van der Voet GB, de Wolff FA. Effect of aluminum chloride,-citrate, and-maltol on the calcium-mediated degradation of neurofilament proteins . Neurotoxicology 1993; 14: 13–18 .[Web of Science][Medline] [Order article via Infotrieve]
• Shea TB, Jung C, Pant HC. Does neurofilament phosphorylation regulate axonal transport? Trends Neurosci 2003; 26: 397–400 .[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Schlaepfer WW, Micko S. Chemical and structural changes of neurofilaments in transected rat sciatic nerve . J Cell Biol 1978; 78: 369–378 .[Abstract/Free Full Text]
• Dubois M, Strazielle C, Julien JP, Lalonde R. Mice with the deleted neurofilament of low molecular weight (Nefl) gene: 2. Effects on motor functions and spatial orientation . J Neurosci Res 2005; 80: 751–758 .[CrossRef][Web of Science][Medline] [Order article via Infotrieve]

Human & Experimental Toxicology, Vol. 25, No. 11, 667-674 (2006)
DOI: 10.1177/0960327106070671


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (10) Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Vahidnia, A Articles by de Wolff, F A Search for Related Content PubMed PubMed Citation Articles by Vahidnia, A Articles by de Wolff, F A Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Arsenic Hazardous Substances DB ARSENIC COMPOUNDS ARSENIC, ELEMENTAL Social Bookmarking                         What's this?