title: Lipid oxidative damage and distribution of inorganic arsenic and its metabolites in the rat nervous system after arsenite exposure: influence of alpha tocopherol supplementation.
abstract: Inorganic arsenic (iAs) exposure causes peripheral neuropathy. Oxidative effects caused by iAs exposure in peripheral nerves have been incompletely characterized. This study analyzed arsenic and lipid oxidative damage in the brain, spinal cord, and sciatic and sensory sural nerves following arsenite exposure. This study also explored whether alpha tocopherol (alpha-TOC) administration mitigates arsenite-induced oxidative damage. Thiobarbituric acid-reactive substance (TBARS) levels and distributions of iAs and its metabolites were evaluated in male Wistar rats following 30d of sodium arsenite exposure (10mg/kg bodyweight (bw)/d, by gavage). A second group also received alpha-TOC (125mg/kg bw/d, by gavage) during the final 20d of arsenite administration. Arsenite exposure caused increased TBARS levels within each region of the nervous system; oxidative stress was most pronounced in the sural and sciatic nerves. In addition there was a positive quadratic relationship between TBARS levels and the concentration of arsenicals found in the nervous system (r(2)=0.878, p<0.001). Dimethylarsenic was the predominant metabolite of iAs found. Animals alpha-TOC-treated had a 1.7-5.2-fold reduction in TBARS levels when compared with rats that received iAs alone. These results suggest that oxidative damage may be the main mechanism of toxicity induced by exposure of the peripheral nervous system to arsenite and that such damage could be attenuated by alpha-TOC-supplementation.
authors.affiliation: Cinvestav, Sección Externa de Toxicología, Av. IPN #2508, Col. San Pedro Zacatenco, México, D.F. 07360, México.
authors.forename: Erika
authors.initials: E
authors.lastname: García-Chávez
authors.forename: Ismael
authors.initials: I
authors.lastname: Jiménez
authors.forename: Bertha
authors.initials: B
authors.lastname: Segura
authors.forename: Luz M
authors.initials: LM
authors.lastname: Del Razo
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001149:Arsenates / Q000633:toxicity*; D020261:Arsenic Poisoning / Q000178:diet therapy* / Q000378:metabolism; D004347:Drug Interactions; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013723:Teratogens / Q000633:toxicity*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D001149:Arsenates; D008054:Lipid Peroxides; D013723:Teratogens; D017392:Thiobarbituric Acid Reactive Substances; D024502:alpha-Tocopherol; C025657:arsenic acid