1B). The second set of experiments was performed to analyze the effect of Met treatment on RS production caused by MeHg in liver slices and mitochondria isolated from

liver slices. Fig. 2 illustrates the levels of DFC-RS production in liver slices (A) and mitochondria isolated from liver slices (B) after 45 min of exposure to Met (50–250 μM). The Selleckchem RG7422 data show that Met pre-treatment, at all concentrations tested, did not cause any effect on DFC-RS production when compared to control values (Figs. 2A and B). Fig. 3 shows the effects of exposure to MeHg or the MeHg–Cys complex on DFC-RS generation in liver slices (A) and mitochondria isolated from liver slices (B). In liver slices, the levels of DFC-RS production were slightly enhanced by exposure to MeHg or the MeHg–Cys complex. However, this difference was not statistically significant (Fig. 3A). In contrast, in the mitochondria isolated from these liver slices, MeHg exposure produced a significant Buparlisib ic50 increase on DFC-RS production when compared to levels found in the control group (Fig. 3B). Furthermore, the DFC-RS production levels were significantly higher in the mitochondria isolated from liver slices that were treated with the MeHg–Cys complex, when compared to mitochondria isolated from slices exposed to MeHg alone (Fig. 3B). Notably, Met pre-treatment was effective in reducing DFC-RS production

only in the mitochondria isolated from slices treated with the MeHg–Cys complex (Fig. 4). The third set of experiments was designed to verify mitochondrial viability by determining the oxygen consumption by the liver slices. Fig. 5A shows that MeHg exposure significantly decreased the oxygen consumption of liver slices as compared to the control group, and that this effect was mafosfamide more pronounced in the liver slices treated with the MeHg–Cys complex. Interestingly, Met pre-treatment effectively prevented the reduction of oxygen consumption in both slices treated with MeHg and slices treated with the

MeHg–Cys complex (Fig. 5B) when compared to control slices (Fig. 5A). A synopsis of MeHg, MeHg–Cys and Met modulation of mitochondria respiration is depicted in Table 1. The final set of experiments was performed to evaluate the cell viability/mitochondria activity in liver slices. Fig. 6 shows that treatment with MeHg alone caused a significant decrease in mitochondrial activity at all tested times (30, 60 and 120 min. Figs. 6A, B and C, respectively) when compared to the control group. At 30 and 60 min, the loss of mitochondrial activity was higher in liver slices exposed to the MeHg–Cys complex when compared to those treated only with MeHg (Figs. 6A and B, respectively). At all times tested, Met pre-treatment prevented mitochondrial dysfunction induced by both MeHg and MeHg–Cys complex exposure (Figs. 6A, B and C).