Organoselenium Bis Selenide Attenuates 3-Nitropropionic Acid-Induced Neurotoxicity in Rats

被引:0
作者
Cristiani F. Bortolatto
Cristiano R. Jesse
Ethel A. Wilhelm
Pietro M. Chagas
Cristina W. Nogueira
机构
[1] Universidade Federal de Santa Maria,Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Departamento de Química, Centro de Ciências Naturais e Exatas
来源
Neurotoxicity Research | 2013年 / 23卷
关键词
Huntington’s disease; 3-Nitropropionic acid; Neurotoxicity; Oxidative stress; Organoselenium; Rats;
D O I
暂无
中图分类号
学科分类号
摘要
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.
引用
收藏
页码:214 / 224
页数:10
相关论文
共 182 条
[21]  
Borlongan CV(2002)Endogenous sodium-potassium ATPase inhibition related biochemical cascade in trisomy 21 and Huntington’s disease: neural regulation of genomic function Neurol India 50 174-180
[22]  
Koutouzis TK(2006)Effect of resveratrol on 3-nitropropionic acid-induced biochemical and behavioural changes: possible neuroprotective mechanisms Behav Pharmacol 17 485-492
[23]  
Freeman TB(2007)Cyclooxygenase inhibition attenuates 3-nitropropionic acid-induced neurotoxicity in rats: possible antioxidant mechanisms Fundam Clin Pharmacol 21 297-306
[24]  
Cahill DW(2000)Effect of exogenous and endogenous antioxidants on 3-nitropropionic acid-induced in vivo oxidative stress and striatal lesions: insights into Huntington’s disease J Neurochem 75 1709-1715
[25]  
Sanberg PR(2010)Glutathione system in young spontaneously hypertensive rats J Physiol Biochem 66 321-327
[26]  
Bradford MM(1990)Determination of carbonyl content in oxidatively modified proteins Methods Enzymol 186 464-478
[27]  
Calberg I(2005)Spectrofluorometric determination of intracellular levels of reactive oxygen species in drug-sensitive and drug-resistant cancer cells using the 2′,7′-dichlorofluorescein diacetate assay Radiat Phys Chem 72 323-331
[28]  
Mannervik B(2005)Oxidative stress in brain aging, neurodegenerative and vascular diseases: an overview J Chromatogr B Analyt Technol Biomed Life Sci 827 65-75
[29]  
Davies S(1990)Effect of oxidants on Na, K, Atpase and its reversal Basic Res Cardiol 185 330-341
[30]  
Ramsden DB(1972)The role of superoxide anion in the autoxidation of epinephrine and simple assay for superoxide J Biol Chem 247 3170-3175