Title: Organochalcogens inhibit mitochondrial complexes I and II in rat brain: possible implications for neurotoxicity.
Authors: Puntel, Robson Luiz; Roos, Daniel Henrique; Seeger, Rodrigo Lopes; Aschner, Michael; Rocha, João Batista Teixeira
Published In Neurotox Res, (2013 Aug)
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.
PubMed ID: 23224748
MeSH Terms: Animals; Brain/drug effects*; Brain/enzymology; Chalcogens/toxicity*; Electron Transport Complex I/antagonists & inhibitors*; Electron Transport Complex I/metabolism; Electron Transport Complex II/antagonists & inhibitors*; Electron Transport Complex II/metabolism; Male; Mitochondrial Membranes/drug effects*; Mitochondrial Membranes/enzymology; Organoselenium Compounds/toxicity*; Rats; Rats, Wistar