Organochalcogens Inhibit Mitochondrial Complexes I and II in Rat Brain: Possible Implications for Neurotoxicity

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.