Does acute exposure to thimerosal, an organic mercury compound, affect the mitochondrial function of an infant model?

BACKGROUND: Thimerosal (TM) is a toxic, organometallic mercury compound (which releases ethyl-mercury-containing compounds in aqueous solutions) used as a preservative in vaccines. Mitochondria are organelle which are highly vulnerable to many chemical compounds, including mercury (Hg) and its derivatives. METHOD: Wistar rats (at 21 days of age) were used to model a child's TM exposure following childhood vaccination, divided in two groups: TM exposed (20 µg/kg/day) and unexposed controls (saline solution), both for 24 h. Atomic Fluorescence Spectrometry was used to quantify the amounts of mercury in tissues. The electron transport chain (ETC) from isolated mitochondria was evaluated using an oxygen electrode. The mitochondrial membrane potential and H2O2 production were analyzed using selective fluorescence probes. The activity of some enzymes (SOD, CAT, GPx, and AChE) and secondary markers of oxidative stress (GSH, GSSG, total free thiol) were also examined in tissues. RESULTS: Hg accumulation in the brain and liver was higher in exposed animals when compared to the control. Liver-isolated mitochondria showed that TM improved respiratory control by 23%; however, states 3 and 4 of the ETC presented a decrease of 16% and 37%, respectively. Furthermore, brain-isolated mitochondria presented an improvement of 61% in respiratory control. Brain enzyme activities were significantly impacted in TM-exposed rats compared to unexposed rats as follows: decreases in SOD (32%) and AChE (42%) and increases in GPx (79%) and CAT (100%). GPx enzyme activity in the liver was significantly increased (37%). Among secondary oxidative stress markers, the brain's total reduced thiol (SH) concentration was significantly increased (41%). CONCLUSION: Acute TM treatment exposure in a Wistar rat model mimicking TM exposure in an infant following childhood vaccination significantly damaged brain bioenergetic pathways. This study supports the ability of TM exposure to preferentially damage the nervous system.

Assessment of thimerosal effects in sublethal concentrations on zebrafish (Danio rerio) embryos exploring NMR-based metabolomics profile.

Thimerosal, a preservative commonly used in the pharmaceutical and cosmetic industry, has raised concerns regarding its potentially toxic effects as an organic mercury compound. Within this context, using an NMR-based metabolomics profile and chemometric analysis, zebrafish embryos were used as an in vivo model to study the effects of thimerosal in metabolic profiles after exposure to sublethal concentrations of the mercury compound. The thimerosal concentrations of 40 and 80 nM were employed, corresponding to 40% and 80% of the LC50, respectively, for zebrafish embryos. The most significant alterations in the metabolic profile included changes in carbohydrates, amino acids, nucleotides, trimethylamine-N-oxide, ethanolamine, betaine, and ethanol. Furthermore, thimerosal exposure affects various metabolic pathways, impairing the nervous system, disrupting protein metabolism, and potentially causing oxidative damage. Therefore, adopting a metabolomics approach in this investigation provided insights into the potentially implicated metabolic pathways contributing to the deleterious effects of thimerosal in biological systems.

Metalloproteomic approach to liver tissue of rats exposed to mercury.

The aims of this study were to identify mercury-associated protein spots in the liver tissue of rats exposed to low concentrations of mercury and to elucidate the physiological and functional aspects of the proteins identified in the protein spots. Therefore, proteomic analysis of the liver tissue of Wistar rats exposed to mercury chloride (4.60 µg kg-1 in Hg2+) was performed for thirty days (Hg-30 group) and sixty days (Hg-60 group). The proteomic profile of the liver tissue of the rats was obtained by two-dimensional electrophoresis (2D-PAGE), and the determinations of total mercury in the liver tissue, pellets and protein spots were performed by graphite furnace atomic absorption spectrometry (GFAAS). ImageMaster 2D Platinum 7.0 software was used to identify the differentially expressed mercury-associated protein spots, which were then characterized by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The determinations by GFAAS indicated a total mercury bioaccumulation of 2812% in the Hg-30 group and 3298% in the Hg-60 group and 10 mercury-associated protein spots with a concentration range of 51 ± 1.0 to 412 ± 6.00 mg kg-1 in the 2D PAGE gels from the liver tissue of the Hg-60 group. The LC-MS/MS analyses allowed the identification of 11 metal binding proteins in mercury-associated protein spots that presented fold change with upregulation >1.5, downregulation < -1.7 or that were expressed only in the Hg-60 group. Using the FASTA sequences of the proteins identified in the mercury-associated protein spots, bioinformatics analyses were performed to elucidate the physiological and functional aspects of the metal binding proteins, allowing us to infer that enzymes such as GSTM2 presented greater mercury concentrations and downregulation < -3; Acaa2 and Bhmt, which showed expression only in the Hg-60 group, among others, may act as potential mercury exposure biomarkers.

Trace-elements, methylmercury and metallothionein levels in Magellanic penguin (Spheniscus magellanicus) found stranded on the Southern Brazilian coast.

Magellanic penguins have been reported as good biomonitors for several types of pollutants, including trace-elements. In this context, selenium (Se), total mercury, methylmercury, inorganic mercury (Hg(inorg)), cadmium (Cd) and lead (Pb), as well as metallothionein (MT) levels, were evaluated in the feathers, liver and kidney of juvenile Magellanic penguins found stranded along the coast of Southern Brazil. The highest concentrations of all trace-elements and methylmercury were found in internal organs. Concentrations of Cd and Se in feathers were extremely low in comparison with their concentrations in soft tissues. The results showed that both Se and MT are involved in the detoxification of trace-elements (Cd, Pb and Hg(inorg)) since statistically significant relationships were found in liver. Conversely, hepatic Se was shown to be the only detoxifying agent for methylmercury.

Mercury distribution in different tissues and trophic levels of fish from a tropical reservoir, Brazil

Concentrations of organic (OrgHg) and inorganic mercury (InorgHg) were assessed in different fish tissues (liver, muscle, kidney, gut and gonads) and trophic levels collected in an impacted tropical reservoir in southeastern Brazil. Organic mercury concentrations in muscle were remarkably higher in the carnivorous species Hoplias malabaricus and Oligosarcus hepsetus. The ratios of OrgHg in relation to total mercury ( percentOrgHg) in muscle also varied according to the species trophic level: 93 percent for carnivores, 84 percent for omnivores, 73 percent for algivores/planktivores and 58 percent for detritivores. The percentOrgHg in the gut tissue of carnivores (78 percent) was much higher than that found in omnivores (30 percent), possibly reflecting a process of trophic biomagnification in the reservoir. On the other hand, the InorgHg concentrations in muscle decreased with the trophic level increase, suggesting that this form of mercury did not biomagnify through the food web. Gonads contained the least total mercury, and approximately all of this mercury was represented by the organic form (83 to 98 percent). The kidney and the liver of all fish species contained less than 50 percent OrgHg. We suggest that the low percentOrgHg in the liver is related to different capacities or strategies of OrgHg detoxification by the fish.(AU)

Concentrações de mercúrio orgânico (OrgHg) e inorgânico (InorgHg) foram avaliadas em diferentes tecidos e níveis tróficos de peixes (fígado, músculo, rim, trato digestivo e gônadas) coletados em um reservatório tropical impactado, no sudeste do Brasil. Concentrações de OrgHg no músculo foram notavelmente maiores em carnívoros (Hoplias malabaricus e Oligosarcus hepsetus). As porcentagens de OrgHg em relação ao mercúrio total ( por centoOrgHg) no músculo também variaram de acordo com o nível trófico das espécies: 93 por cento para os carnívoros, 84 por cento para os onívoros, 73 por cento para os algívoros/planctívoros e 58 por cento para os peixes detritívoros. Além disso, a por centoOrgHg encontrada no trato digestivo dos peixes carnívoros (78 por cento) foi substancialmente superior a encontrada nos onívoros (30 por cento), possivelmente refletindo um processo de biomagnificação trófica no reservatório. Por outro lado, as concentrações de InorgHg no músculo diminuíram com o aumento do nível trófico, sugerindo que esta forma do mercúrio não biomagnificou ao longo da cadeia alimentar. As gônadas apresentaram as menores concentrações de mercúrio total e grande parte deste estava na forma orgânica (83 a 98 por cento). Por outro lado, rins e fígado de todas as espécies de peixes apresentaram menos que 50 por cento de OrgHg. Sugere-se que a baixa por centoOrgHg no fígado possa estar relacionada às diferentes capacidades ou estratégias de destoxificação do OrgHg nesses peixes(AU)

Mercury distribution in different tissues and trophic levels of fish from a tropical reservoir, Brazil

Concentrations of organic (OrgHg) and inorganic mercury (InorgHg) were assessed in different fish tissues (liver, muscle, kidney, gut and gonads) and trophic levels collected in an impacted tropical reservoir in southeastern Brazil. Organic mercury concentrations in muscle were remarkably higher in the carnivorous species Hoplias malabaricus and Oligosarcus hepsetus. The ratios of OrgHg in relation to total mercury ( percentOrgHg) in muscle also varied according to the species trophic level: 93 percent for carnivores, 84 percent for omnivores, 73 percent for algivores/planktivores and 58 percent for detritivores. The percentOrgHg in the gut tissue of carnivores (78 percent) was much higher than that found in omnivores (30 percent), possibly reflecting a process of trophic biomagnification in the reservoir. On the other hand, the InorgHg concentrations in muscle decreased with the trophic level increase, suggesting that this form of mercury did not biomagnify through the food web. Gonads contained the least total mercury, and approximately all of this mercury was represented by the organic form (83 to 98 percent). The kidney and the liver of all fish species contained less than 50 percent OrgHg. We suggest that the low percentOrgHg in the liver is related to different capacities or strategies of OrgHg detoxification by the fish.(AU)

Concentrações de mercúrio orgânico (OrgHg) e inorgânico (InorgHg) foram avaliadas em diferentes tecidos e níveis tróficos de peixes (fígado, músculo, rim, trato digestivo e gônadas) coletados em um reservatório tropical impactado, no sudeste do Brasil. Concentrações de OrgHg no músculo foram notavelmente maiores em carnívoros (Hoplias malabaricus e Oligosarcus hepsetus). As porcentagens de OrgHg em relação ao mercúrio total ( por centoOrgHg) no músculo também variaram de acordo com o nível trófico das espécies: 93 por cento para os carnívoros, 84 por cento para os onívoros, 73 por cento para os algívoros/planctívoros e 58 por cento para os peixes detritívoros. Além disso, a por centoOrgHg encontrada no trato digestivo dos peixes carnívoros (78 por cento) foi substancialmente superior a encontrada nos onívoros (30 por cento), possivelmente refletindo um processo de biomagnificação trófica no reservatório. Por outro lado, as concentrações de InorgHg no músculo diminuíram com o aumento do nível trófico, sugerindo que esta forma do mercúrio não biomagnificou ao longo da cadeia alimentar. As gônadas apresentaram as menores concentrações de mercúrio total e grande parte deste estava na forma orgânica (83 a 98 por cento). Por outro lado, rins e fígado de todas as espécies de peixes apresentaram menos que 50 por cento de OrgHg. Sugere-se que a baixa por centoOrgHg no fígado possa estar relacionada às diferentes capacidades ou estratégias de destoxificação do OrgHg nesses peixes(AU)