title: Organochalcogens inhibit mitochondrial complexes I and II in rat brain: possible implications for neurotoxicity.
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 activity, with Ebs, (PhSe)₂ and (PhTe)₂ effectively oxidising critical thiol groups of these complexes.
authors.affiliation: Universidade Federal do Pampa, Campus Uruguaiana BR-472 Km 7, Uruguaiana, RS 97500-970, Brazil. robson_puntel@yahoo.com.br
authors.forename: Robson Luiz
authors.initials: RL
authors.lastname: Puntel
authors.forename: Daniel Henrique
authors.initials: DH
authors.lastname: Roos
authors.forename: Rodrigo Lopes
authors.initials: RL
authors.lastname: Seeger
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
authors.forename: João Batista Teixeira
authors.initials: JB
authors.lastname: Rocha
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D018011:Chalcogens / Q000633:toxicity*; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D042963:Electron Transport Complex II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000201:enzymology; D016566:Organoselenium Compounds / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018011:Chalcogens; D016566:Organoselenium Compounds; D042963:Electron Transport Complex II; D042967:Electron Transport Complex I