Abstract
Mercury is a severe environmental pollutant with neurotoxic effects, especially when exposed for long periods. Although there are several evidences regarding mercury toxicity, little is known about inorganic mercury (IHg) species and cerebellum, one of the main targets of mercury associated with the neurological symptomatology of mercurial poisoning. Besides that, the global proteomic profile assessment is a valuable tool to screen possible biomarkers and elucidate molecular targets of mercury neurotoxicity; however, the literature is still scarce. Thus, this study aimed to investigate the effects of long-term exposure to IHg in adult rats’ cerebellum and explore the modulation of the cerebellar proteome associated with biochemical and functional outcomes, providing evidence, in a translational perspective, of new mercury toxicity targets and possible biomarkers. Fifty-four adult rats were exposed to 0.375 mg/kg of HgCl2 or distilled water for 45 days using intragastric gavage. Then, the motor functions were evaluated by rotarod and inclined plane. The cerebellum was collected to quantify mercury levels, to assess the antioxidant activity against peroxyl radicals (ACAPs), the lipid peroxidation (LPO), the proteomic profile, the cell death nature by cytotoxicity and apoptosis, and the Purkinje cells density. The IHg exposure increased mercury levels in the cerebellum, reducing ACAP and increasing LPO. The proteomic approach revealed a total 419 proteins with different statuses of regulation, associated with different biological processes, such as synaptic signaling, energy metabolism and nervous system development, e.g., all these molecular changes are associated with increased cytotoxicity and apoptosis, with a neurodegenerative pattern on Purkinje cells layer and poor motor coordination and balance. In conclusion, all these findings feature a neurodegenerative process triggered by IHg in the cerebellum that culminated into motor functions deficits, which are associated with several molecular features and may be related to the clinical outcomes of people exposed to the toxicant.
Highlights
Mercury is a hazardous toxic pollutant distributed in the environment and is considered a severe public health concern [1,2]
This study is the first investigation that brings to the literature evidence regarding the cerebellar global proteomic profile of rats exposed to IHg that underlies the IHg-induced neurotoxicity
Our results demonstrate the IHg exposure triggers oxidative stress and cell death by cytotoxicity and apoptosis, besides the reduction in Purkinje cells density in the cerebellum of rats
Summary
Mercury is a hazardous toxic pollutant distributed in the environment and is considered a severe public health concern [1,2]. Humans are subjected to the mercurial compound by different sources because of anthropogenic activities, such as occupational exposure and environmental contamination by illegal gold mining that contaminates fish and seafood [3,4]. Elemental mercury (Hg0) and methylmercury (MeHg) are considered the main species of exposure in occupational and environmental (via seafood) outbreaks, respectively [3,4]. Even in the case of MeHg exposure, consequences would be due to inorganic mercury (IHg), since the latter specie was detected in both contaminated food and cells of central nervous system (CNS) origin [5,6]. Considering the presence of IHg in fish, this becomes a serious public health problem since those who consume them, especially populations whose food bases are these items [7], are subject to prolonged exposure. Due to its toxicokinetic characteristics, after absorption, kidneys [8] and the blood and cells from the human central nervous system (CNS) are affected by IHg poisoning [9,10,11]
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