Organochalcogens Inhibit Mitochondrial Complexes I and II in Rat Brain: Possible Implications for Neurotoxicity
- PDF / 372,115 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 112 Downloads / 175 Views
ORIGINAL ARTICLE
Organochalcogens Inhibit Mitochondrial Complexes I and II in Rat Brain: Possible Implications for Neurotoxicity Robson Luiz Puntel • Daniel Henrique Roos Rodrigo Lopes Seeger • Michael Aschner • Joa˜o Batista Teixeira Rocha
•
Received: 18 May 2012 / Revised: 20 November 2012 / Accepted: 21 November 2012 / Published online: 6 December 2012 Ó Springer Science+Business Media New York 2012
Abstract Organochalcogens, such as organoselenium and organotellurium compounds, can be neurotoxic to rodents. Since mitochondrial dysfunction plays a pivotal role in neurological disorders, the present study was designed to test the hypothesis that rat brain mitochondrial complexes (I, II, I–III, II–III and IV) could be molecular targets of organochalcogens. The results show that organochalcogens caused statistically significant inhibition of mitochondrial complex I activity, which was prevented by preincubation with NADH and fully blunted by reduced glutathione (GSH). Mitochondrial complex II activity remained unchanged in response to (PhSe)2 treatment. Ebs and (PhTe)2 caused a significant concentration-dependent inhibition of complex II that was also blunted by GSH. Mitochondrial complex IV activity was not modified by organochalcogens. Collectively, Ebs, (PhSe)2 and (PhTe)2 were more effective inhibitors of brain mitochondrial complex I than of complex II, whereas they did not affect complex IV. These observations are consistent with organochalcogens inducing mitochondrial complex I and II inhibition via their thiol-oxidase-like
R. L. Puntel (&) Universidade Federal do Pampa, Campus Uruguaiana BR-472 Km 7, Uruguaiana, RS 97500-970, Brazil e-mail: [email protected] D. H. Roos R. L. Seeger J. B. T. Rocha (&) Departamento de Quı´mica, Centro de Cieˆncias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil e-mail: [email protected] M. Aschner Departments of Pediatrics and Pharmacology, and the Kennedy Center for Research on Human Development, Vanderbilt University Medical Center, Nashville, TN, USA
activity, with Ebs, (PhSe)2 and (PhTe)2 effectively oxidising critical thiol groups of these complexes. Keywords Thiol-oxidase-like activity Thiol oxidation Molecular target Brain mitochondria
Introduction Organochalcogenides, such as organoselenium and organotellurium compounds, are promising pharmacological agents (Nogueira and Rocha 2010; Nogueira et al. 2004). They have been widely studied because of their potential antioxidant capacity (Arteel and Sies 2001; Barbosa et al. 2008, 2006; de Bem et al. 2009; de Freitas et al. 2009; Hort et al. 2011; Moretto et al. 2007; Nogueira and Rocha 2011, 2010; Parnham and Graf 1991; Prauchner et al. 2011; Prigol et al. 2008; Puntel et al. 2007; Rossato et al. 2002). However, at high dosages, both organoselenium and organotellurium compounds are neurotoxic (Jacques-Silva et al. 2001; Maciel et al. 2000; Nogueira et al. 2001, 2003; Stangherlin et al. 2005). The documented antioxidant activity of the organochalcogens ha
Data Loading...
