Efeitos da exposição ao mercúrio e derivados sobre a bioenergética mitocondrial e estresse oxidativo no desenvolvimento da hipertensão

Abstract

Hypertension is a systemic disease that affects a large part of the world's population and its development does not have a single factor related to its origin. Environmental factors such as exposure to mercury species may be one of the reasons that trigger this condition. In this context, studies indicate that mitochondria play a central role in the development of hypertension due to oxidative stress, which can be enhanced in the presence of mercury. Thimerosal (TM) is an organic mercury species present in vaccines and dermatological formulations as a preservative, which in an aqueous medium can release ethylmercury. Thus, due to the lack of studies addressing the effects of mercury contamination on the mitochondrial bioenergetics of spontaneously hypertensive rats (SHR), we decided to evaluate which parameters could be varied by exposing SHR rats to TM with emphasis on the mitochondrial bioenergetics of two organs: liver and brain. The animals were divided into two groups; both were treated for 24 h with TM solution (0.5 mg kg-1 ) or aqueous saline solution (control). The electron transport chain (ETC) of isolated liver and brain mitochondria were evaluated using an oxygen electrode. Liver and brain mitochondrial integrity were analyzed by swelling and membrane potential. Mitochondrial oxidative and nitrosative stress were analyzed using DCF (non-selective ROS), amplex-red (H2O2) and DAF-FM (•NO) probes. In addition, oxidative stress markerssuch as antioxidant enzyme activity (SOD and CAT), total content of sulfhydryl groups (SH), malondialdehyde (MDA), GSH/GSSG ratio and carbonyl protein content (LPO) were also quantified. The project was approved by CEUA/UFAL (23/2021). Mitochondrial respiration experiments showed that using complex I as a substrate, the respiratory control (CR) of the group exposed to TM showed a decrease of 40% for the liver and 23% for the brain. However, when compared to the control group, in the resting and uncoupled states for the liver, there was a superior performance of the control group in relation to the treated group (65 and 48%, respectively). On the other hand, for the brain, these results showed no significant difference. When evaluating mitochondrial integrity, membrane potential and liver swelling, we found no differences between groups. In the same vein, in the liver, the generation of total ROS and mitochondrial •NO showed no statistical difference between groups. Liver SOD activity showed a 59% decrease compared to the exposed group compared to the control group; on the other hand, the other markers showed no difference between the groups. In the brain, no significant differences were found in mitochondrial integrity (membrane potential and swelling) between groups, as well as between mitochondrial generation of ROS and •NO. On the other hand, still in the brain, the activity of the antioxidant enzymes SOD and CAT showed an increase of 100 and 83% for the treated group, respectively, however for other stress markers such as SH and MDA there was a decrease of 46 and 41%, respectively. (treated vs. control). Overall, our findings suggest that acute exposure to TM negatively contributes to damage to the redox status and functionality of the mitochondria, being responsible for the ETC uncoupling, which may be one of the causes for the mitochondrial dysfunction that triggers hypertension.