title: Organoselenium bis selenide attenuates 3-nitropropionic acid-induced neurotoxicity in rats.
abstract: This study was designed to evaluate the effects of bis selenide on Huntington disease (HD)-like signs induced by 3-nitropropionic acid (3-NP) in rats. To this aim, rats were treated for 4 days with bis selenide (5 or 20 mg/kg/day, per oral) 30 min before 3-NP (20 mg/kg/day, intraperitoneally). The body weight gain, locomotor activity, motor coordination, and biochemical parameters in striatal preparations were assessed 24 h after the last injection of 3-NP. The highest dose of bis selenide was effective in protecting against body weight loss and motor coordination deficit induced by 3-NP. The impairment of locomotor activity caused by 3-NP was abolished by bis selenide at both doses. Bis selenide (5 and 20 mg/kg) partially restored succinate dehydrogenase activity inhibited after 3-NP exposure. The dose of 20 mg/kg of bis selenide recovered partially δ-aminolevulinic acid dehydratase activity, and totally Na(+), K(+)-ATPase activity, two sulfhydryl enzymes sensitive to oxidizing agents, which had their activities inhibited by 3-NP. Also, 3-NP led to an increase in protein carbonyl levels and glutathione reductase activity and inhibited catalase activity-alterations that were reversed by bis selenide administration at both doses. The highest dose of bis selenide was effective against the increase of RS levels, the depletion of reduced glutathione content, and the inhibition of glutathione peroxidase activity induced by 3-NP. Bis selenide was not effective against inhibition of SOD activity caused by 3-NP. These findings demonstrate that bis selenide elicited protective effects against HD-like signs induced by 3-NP in rats.
authors: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS CEP 97105-900, Brazil.
authors: Cristiani F
authors: CF
authors: Bortolatto
authors: Cristiano R
authors: CR
authors: Jesse
authors: Ethel A
authors: EA
authors: Wilhelm
authors: Pietro M
authors: PM
authors: Chagas
authors: Cristina W
authors: CW
authors: Nogueira
mesh_terms: D000818:Animals; D001259:Ataxia / Q000188:drug therapy* / Q000201:enzymology; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D042963:Electron Transport Complex II / Q000037:antagonists & inhibitors*; D005106:Exploratory Behavior / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006816:Huntington Disease / Q000188:drug therapy*; D008297:Male; D015394:Molecular Structure; D009419:Nerve Tissue Proteins / Q000032:analysis; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D009574:Nitro Compounds / Q000037:antagonists & inhibitors* / Q000633:toxicity; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011422:Propionates / Q000037:antagonists & inhibitors* / Q000633:toxicity; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D045442:Rotarod Performance Test; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors; D015430:Weight Gain / Q000187:drug effects
chemical_list: C533977:(Z)-2,3-bis(4-chlorophenylselanyl)prop-2-en-1-ol; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D016566:Organoselenium Compounds; D011422:Propionates; D017382:Reactive Oxygen Species; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D005978:Glutathione; C015392:3-nitropropionic acid