Mercury

“Thimerosal (TH), an ethylmercury complex of thiosalicylic acid has been used as preservative in vaccines. In vitro neurotoxicity of TH at high nM concentrations has been reported. Although a number of toxicological experiments demonstrated high affinity of mercury to thiol groups of the extracellular amino acids and proteins that may decrease concentration of free TH in the organism, less is known about the role of interactions between proteins and amino acids in protection against TH neurotoxicity. In the present study we examined whether the presence of serum proteins and of l-cysteine (Cys), d,l-homocysteine (Hcy), N-acetyl cysteine (NAC), l-methionine (Met) and glutathione (GSH) in the incubation medium affects the TH-induced changes in the viability, the intracellular levels of calcium and zinc and mitochondrial membrane potential in primary cultures of rat cerebellar granule cells. The cells were exposed to 500 nM TH for 48 h or to 15-25 ?M TH for 10 min. Our results demonstrated a decrease in the cells viability evoked by TH, which could be prevented partially by serum proteins, albumin or in a dose-dependent manner by 60, 120 or 600 ?M Cys, Hcy, NAC and GSH, but not by Met. This neuroprotection was less pronounced in the presence of proteins. Incubation of neurons with TH also induced the rise in the intracellular calcium and zinc concentration and decrease in mitochondrial membrane potential, and these effects were abolished by all the sulfur containing compounds studied and administered at 600 ?M concentration, except Met. The loss of the ethylmercury moiety from TH as a result of interaction with thiols studied was monitored by (1)H NMR spectroscopy. This extracellular process may be responsible for the neuroprotection seen in the cerebellar cell cultures, but also provides a molecular pathway for redistribution of TH-derived toxic ethylmercury in the organism. In conclusion, these results confirmed that proteins and sulfur-containing amino acids applied separately reduce TH neurotoxicity, while their combination modulates in more complex way neuronal survival in the presence of TH.”

“The organomercurial, thimerosal, is at the center of medical controversy as a suspected factor contributing to neurodevelopmental disorders in children. Many neurotoxic effects of thimerosal have been described, but its interaction with principal excitatory and inhibitory neurotransmiter systems is not known. We examined, using electrophysiological recordings, thimerosal effects on GABA and NMDA-evoked currents in cultured hippocampal neurons. After brief (3 to 10 min) exposure to thimerosal at concentrations up to 100 ?M, there was no significant effect on GABA or NMDA-evoked currents. However, following exposure for 60-90 min to 1 or 10 ?M thimerosal, there was a significant decrease in NMDA-induced currents (p<0.05) and GABAergic currents (p<0.05). Thimerosal was also neurotoxic, damaging a significant proportion of neurons after 60-90 min exposure; recordings were always conducted in the healthiest looking neurons. Mercuric chloride, at concentrations 1 ?M and above, was even more toxic, killing a large proportion of cells after just a few minutes of exposure. Recordings from a few sturdy cells revealed that micromolar mercuric chloride markedly potentiated the GABAergic currents (p<0.05), but reduced NMDA-evoked currents (p<0.05). The results reveal complex interactions of thimerosal and mercuric ions with the GABA(A) and NMDA receptors. Mercuric chloride act rapidly, decreasing electrophysiological responses to NMDA but enhancing responses to GABA, while thimerosal works slowly, reducing both NMDA and GABA responses. The neurotoxic effects of both mercurials are interwoven with their modulatory actions on GABA(A) and NMDA receptors, which most likely involve binding to these macromolecules.”

“Methylmercury (Met-Hg) is one the most toxic forms of Hg, with a considerable range of harmful effects on humans. Sodium ethyl mercury thiosalicylate, thimerosal (TM) is an ethylmercury (Et-Hg)-containing preservative that has been used in manufacturing vaccines in many countries. Whereas the behavior of Met-Hg in humans is relatively well known, that of ethylmercury (Et-Hg) is poorly understood. The present study describes the distribution of mercury as (-methyl, -ethyl and inorganic mercury) in rat tissues (brain, heart, kidney and liver) and blood following administration of TM or Met-Hg. Animals received one dose/day of Met-Hg or TM by gavage (0.5 mg Hg/kg). Blood samples were collected after 6, 12, 24, 48, 96 and 120 h of exposure. After 5 days, the animals were killed, and their tissues were collected. Total blood mercury (THg) levels were determined by ICP-MS, and methylmercury (Met-Hg), ethylmercury (Et-Hg) and inorganic mercury (Ino-Hg) levels were determined by speciation analysis with LC-ICP-MS. Mercury remains longer in the blood of rats treated with Met-Hg compared to that of TM-exposed rats. Moreover, after 48 h of the TM treatment, most of the Hg found in blood was inorganic. Of the total mercury found in the brain after TM exposure, 63% was in the form of Ino-Hg, with 13.5% as Et-Hg and 23.7% as Met-Hg. In general, mercury in tissues and blood following TM treatment was predominantly found as Ino-Hg, but a considerable amount of Et-Hg was also found in the liver and brain. Taken together, our data demonstrated that the toxicokinetics of TM is completely different from that of Met-Hg. Thus, Met-Hg is not an appropriate reference for assessing the risk from exposure to TM-derived Hg. It also adds new data for further studies in the evaluation of TM toxicity.”

“Thimerosal added to some pediatric vaccines is suspected in pathogenesis of several neurodevelopmental disorders. Our previous study showed that thimerosal administered to suckling rats causes persistent, endogenous opioid-mediated hypoalgesia. Here we examined, using immunohistochemical staining technique, the density of μ-opioid receptors (MORs) in the brains of rats, which in the second postnatal week received four i.m. injections of thimerosal at doses 12, 240, 1,440 or 3,000 μg Hg/kg. The periaqueductal gray, caudate putamen and hippocampus were examined. Thimerosal administration caused dose-dependent statistically significant increase in MOR densities in the periaqueductal gray and caudate putamen, but decrease in the dentate gyrus, where it was accompanied by the presence of degenerating neurons and loss of synaptic vesicle marker (synaptophysin). These data document that exposure to thimerosal during early postnatal life produces lasting alterations in the densities of brain opioid receptors along with other neuropathological changes, which may disturb brain development.”

“This study assessed the practice of disposing of waste from the eight dental clinics of Obafemi Awolowo University Teaching Complex, Ile-Ife, Nigeria. All the cleaners (14) in the hospitals were surveyed through questionnaire. Information obtained from the cleaners included socio-economic characteristics (biodata), personal protection, facilities available for them to work with and job satisfaction. Two soil samples were obtained from the open dump site (0.15 and 0.30 m depth) and two water samples were also collected (at 0.00 and 50.00 m) within the vicinity of the dump site. Both the soil and water samples were taken to the central science laboratory for chemical analyses. Ten (71.4%) of the 14 cleaners were not satisfied with their job. The laboratory findings suggested a very high content of lead, chromium, mercury, cadmium and manganese in both soil and water samples in comparison with the Nigerian Federal Environmental Protection Agency standards. The study concludes that the use of tooth-coloured restorative materials and digital X-ray facility to serve as alternatives to the generation of these wastes is recommended and that farming activities should not be allowed in the area until an audit of the soil and water have been performed.”

“Thimerosal, an organomercurial added as a preservative to some vaccines, is a suspected iatrogenic factor, possibly contributing to paediatric neurodevelopmental disorders including autism. We examined the effects of early postnatal administration of thimerosal (four i.m. injections, 12 or 240 ?g THIM-Hg/kg, on postnatal days 7, 9, 11 and 15) on brain pathology in Wistar rats. Numerous neuropathological changes were observed in young adult rats which were treated postnatally with thimerosal. They included: ischaemic degeneration of neurons and “dark” neurons in the prefrontal and temporal cortex, the hippocampus and the cerebellum, pathological changes of the blood vessels in the temporal cortex, diminished synaptophysin reaction in the hippocampus, atrophy of astroglia in the hippocampus and cerebellum, and positive caspase-3 reaction in Bergmann astroglia. These findings document neurotoxic effects of thimerosal, at doses equivalent to those used in infant vaccines or higher, in developing rat brain, suggesting likely involvement of this mercurial in neurodevelopmental disorders.”

“Thimerosal, an ethyl mercury compound, is used worldwide as a vaccine preservative. We previously observed that the mercury concentration in mouse brains did not increase with the clinical dose of thimerosal injection, but the concentration increased in the brain after the injection of thimerosal with lipopolysaccharide, even if a low dose of thimerosal was administered. Thimerosal may penetrate the brain, but is undetectable when a clinical dose of thimerosal is injected; therefore, the induction of metallothionein (MT) messenger RNA (mRNA) and protein was observed in the cerebellum and cerebrum of mice after thimerosal injection, as MT is an inducible protein. MT-1 mRNA was expressed at 6 and 9 h in both the cerebrum and cerebellum, but MT-1 mRNA expression in the cerebellum was three times higher than that in the cerebrum after the injection of 12 microg/kg thimerosal. MT-2 mRNA was not expressed until 24 h in both organs. MT-3 mRNA was expressed in the cerebellum from 6 to 15 h after the injection, but not in the cerebrum until 24 h. MT-1 and MT-3 mRNAs were expressed in the cerebellum in a dose-dependent manner. Furthermore, MT-1 protein was detected from 6 to 72 h in the cerebellum after 12 microg/kg of thimerosal was injected and peaked at 10 h. MT-2 was detected in the cerebellum only at 10 h. In the cerebrum, little MT-1 protein was detected at 10 and 24 h, and there were no peaks of MT-2 protein in the cerebrum. In conclusion, MT-1 and MT-3 mRNAs but not MT-2 mRNA are easily expressed in the cerebellum rather than in the cerebrum by the injection of low-dose thimerosal. It is thought that the cerebellum is a sensitive organ against thimerosal. As a result of the present findings, in combination with the brain pathology observed in patients diagnosed with autism, the present study helps to support the possible biological plausibility for how low-dose exposure to mercury from thimerosal-containing vaccines may be associated with autism.”

“Several cases of skin sensitization have been reported following the application of thimerosal, which is composed of ethyl mercury and thiosalicylic acid (TSA). However, few in vitro studies have been carried out on human dendritic cells (DCs) which play an essential role in the initiation of allergic contact dermatitis. The aim of the present study was to identify the effect of thimerosal and other mercury compounds on human DCs. To address this purpose, DCs derived from monocytes (mono-DCs) were used. Data show that thimerosal and mercury derivatives induced DC activation, as monitored by CD86 and HLA-DR overexpression associated with the secretion of tumor necrosis factor alpha and interleukin 8, similarly to lipopolysaccharide and the sensitizers, 1-chloro-2,4-dinitrobenzene (DNCB) and nickel sulfate, which were used as positive controls. In contrast, TSA, the non-mercury part of thimerosal, as well as dichloronitrobenzene, a DNCB negative control, and the irritant, sodium dodecyl sulfate, had no effect. Moreover, oxidative stress, monitored by ROS induction and depolarization of the mitochondrial membrane potential, was induced by thimerosal and mercury compounds, as well as DNCB, in comparison with hydrogen peroxide, used as a positive control. The role of thiol oxidation in the initiation of mono-DC activation was confirmed by a pre-treatment with N-acetyl-l-cysteine which strongly decreased chemical-induced CD86 overexpression. These data are in agreement with several clinical observations of the high relevance of thimerosal in patch-test reactions and prove that human mono-DCs are useful in vitro tools for determining the allergenic potency of chemicals.”

“The aim was to report on the longevity of restorations placed using the atraumatic restorative treatment (ART) approach compared with that of equivalent placed amalgam restorations. Five databases were systematically searched for articles up to 16 March 2009. Inclusion criteria: (1) titles/abstracts relevant to the topic; (2) published in English; (3) reporting on 2-arm longitudinal in vivo trials; (4) minimum follow-up period of 12 months. Exclusion criteria: (1) insufficient random or quasi-random allocation of study subjects; (2) not all entered subjects accounted for at trial conclusion; (3) subjects of both groups not followed up in the same way. Fourteen from the initial search of 164 articles complied with these criteria and were selected for review. From these, seven were rejected and seven articles reporting on 27 separate datasets, accepted. Only identified homogeneous datasets were combined for meta-analysis. From the 27 separate computable dichotomous datasets, four yielded a statistically significant improvement of longevity of ART versus amalgam restorations: posterior class V, 28% over 6.3 years; posterior class I, 6% after 2.3 years and 9% after 4.3 years; posterior class II, 61% after 2.3 years. Studies investigating restorations placed in the primary dentition showed no significant differences between the groups after 12 and 24 months. In the permanent dentition, the longevity of ART restorations is equal to or greater than that of equivalent amalgam restorations for up to 6.3 years and is site-dependent. No difference was observed in primary teeth. More trials are needed in order to confirm these results.”