title: Mitochondrial electron transfer chain complexes inhibition by different organochalcogens.
abstract: Mitochondrial dysfunction plays a pivotal role in the cell toxicology and death decision. The aim of the present study was to investigate the effect of three organocompounds (ebselen [Ebs], diphenyl diselenide [(PhSe)(2)] and diphenyl ditelluride [(PhTe)(2)]) on mitochondrial complexes (I, II, I-III, II-III and IV) activity from rat liver and kidney to determine their potential role as molecular targets of organochalcogens. All studied organochalcogens caused a statistically significant inhibition of the mitochondrial complex I activity. Ebs and (PhTe)(2) caused a statistically significant inhibition of the mitochondrial complex II activity in both hepatic and renal membranes. Hepatic mitochondrial complex II activity was practically unchanged by (PhSe)(2), whereas it significantly inhibited renal complex II activity. Mitochondrial complex IV activity was practically unchanged by the organochalcogens. Furthermore, organochalcogens inhibited the mitochondrial respiration supported by complex I or complex II substrates. The inhibitory effect of Ebs, (PhSe)(2) and (PhTe)(2) on mitochondrial complex I was prevented by NADH, but it was not prevented by catalase (CAT) and/or superoxide dismutase (SOD). Additionally, the organochalcogens-induced inhibition of complex I and II was completely reversed by reduced glutathione (GSH). In conclusion, Ebs, (PhSe)(2) and (PhTe)(2) were more effective inhibitors of renal and hepatic mitochondrial complex I than complex II, whereas complexes III and IV were little modified by these compounds. Taking into account the presented results, we suggest that organochalcogen-induced mitochondrial complexes I and II inhibition can be mediated by their thiol oxidation activity, i.e., Ebs, (PhSe)(2) and (PhTe)(2) can oxidize critical thiol groups from mitochondrial complexes I and II. So, mitochondrial dysfunction can be considered an important factor in the toxicity of Ebs, (PhSe)(2) and (PhTe)(2).
authors.affiliation: Universidade Federal do Pampa - Campus Uruguaiana BR-472 Km 7, Uruguaiana 97500-970, RS, Brazil. robson_puntel@yahoo.com.br
authors.forename: Robson L
authors.initials: RL
authors.lastname: Puntel
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Roos
authors.forename: Rodrigo Lopes
authors.initials: RL
authors.lastname: Seeger
authors.forename: João B T
authors.initials: JB
authors.lastname: Rocha
mesh_terms: D000818:Animals; D001393:Azoles / Q000633:toxicity*; D001555:Benzene Derivatives / Q000633:toxicity*; D004579:Electron Transport; D045222:Electron Transport Chain Complex Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054833:Isoindoles; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009942:Organometallic Compounds / Q000633:toxicity*; D016566:Organoselenium Compounds / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001393:Azoles; D001555:Benzene Derivatives; D045222:Electron Transport Chain Complex Proteins; D054833:Isoindoles; D009942:Organometallic Compounds; D016566:Organoselenium Compounds; C434247:diphenylditelluride; C061132:diphenyldiselenide; C042986:ebselen