9A and B). Ebs (25 μM), (PhSe)2 (50 μM), and (PhTe)2 (50 μM) inhibited oxygen consumption in intact liver mitochondria supported either by pyruvate/glutamate (complex I substrates; Fig. 10A) or succinate (complex II substrate; Fig. 10B) as substrates. For mitochondrial oxygen consumption, the inhibitory potency order was Ebs ∼ (PhTe)2 > (PhSe)2, independent of the substrate used. In fact, Ebs and (PhTe)2 completely inhibits oxygen consumption, whereas (PhSe)2 was less active. Taking into account, the results obtained with intact mitochondria are in accordance with our findings using mitochondrial membranes (isolated complexes

assay). The results presented here indicate that the hepatic and renal toxicity of organochalcogens can be, at least in part, mediated Trichostatin A molecular weight by mitochondrial dysfunction via inhibition of different mithochondrial complexes, which can explain our previous results (Puntel et al., 2010). Here we

found that mitochondrial complex I was the key complex targeted by the organocompounds (almost 100% inhibited), followed by the complex II, whereas the inhibition of complex III and complex IV was negligible. Furthermore, both hepatic and renal mitochondrial preparations seem to be similarly inhibited by organochalcogens. Alectinib In fact, despite of different susceptibility of liver and kidney tissues after in vitro or in vivo exposure to organochalcogens ( Nogueira and Rocha, 2010 and Nogueira and Rocha, 2011), isolated hepatic Sitaxentan and renal mitochondria tended to respond similarly to the inhibitory properties of organochalcogens. Thus we suggest that the differences in the tissues susceptibility when exposed to organochalcogens ( Nogueira and Rocha, 2010 and Nogueira and Rocha, 2011) can be associated with other factors, such as differential

distribution and metabolism of organochalcogens in these tissues. Moreover, here we have used mitochondrial membranes in order to study the direct effect of organochalcogens on the complexes activity to avoid indirect effects of organochalcogen on complexes via modification of mitochondrial functionality (extent of polarization, presence of additional membrane barriers, etc., for details see (Puntel et al., 2010)). We know that the amounts or activities of specific complexes and enzymes can be useful to test specific hypotheses but should generally be held in reserve and not used as the primary assay for mitochondrial dysfunction (Brand and Nicholls, 2011). Hence, oxygen consumption data using intact mitochondria (Fig. 10) validated our findings with mitochondrial membranes and suggested that the inhibition of mitochondrial complexes is involved in the reduction of oxygen consumption by intact mitochondria.