Mercury

“Thimerosal is one of the most widely used preservatives and has been reported to cause chemically mediated side effects. However, the mechanism of the side effects is not clearly understood yet. In the present study, we showed that HeLa S cells treated by thimerosal generated reactive oxygen species (ROS). Thimerosal-generated ROS stimulated the tyrosine phosphorylation of focal adhesion kinase (FAK) and also induced cytoskeletal changes. Pretreatment with intracellular calcium chelator, BAPTA did not block the thimerosal-mediated FAK tyrosine phosphorylation. On the other hand, either FAK inhibitor, tyrphostin or ROS scavenger, N-acetyl-L-cysteine (NAC) suppressed the tyrosine phosphorylation and cytoskeletal changes. These results suggest that thimerosal seems to induce FAK tyrosine phosphorylation and cytoskeletal changes by ROS generation but not by intracellular calcium mobilization. We think the present finding can be an important clue to understanding the mechanism of thimerosal-mediated side effects, such as contact dermatitis, and allergy.”

“Thimerosal (o-Ethylmercurithio)benzoic acid, TMS), a membrane-impermeable, sulfhydryl-oxidizing agent, has been described to increase the K+ current IKs in KCNE1-injected Xenopus laevis oocytes. Since there are no cysteine residues in the extracellular domain of KCNE1, it has been proposed that TMS interacts with its partner protein KCNQ1. The aim of this study was therefore to investigate the interaction of TMS with KCNQ1 and the respective K+current IK. In CHO cells stably transfected with KCNQ1/KCNE1, TMS increased IKs, whereas in CHO cells expressing KCNQ1 alone, TMS initially decreased IK. TMS also affected the cytosolic pH (pHi) and the cytosolic Ca2+ activity ([Ca2+]i) in these cells. TMS slowly decreased pHi. With a short delay, TMS increased [Ca2+]i by store depletion and capacitative influx. The time course of the effects of TMS on pHi and [Ca2+]i did not correlate with the effect of TMS on IK. We therefore anticipated a different mode of action by TMS and investigated the influence of TMS on cysteine residues of KCNQ1. For this purpose, KCNQ1wt and two mutants lacking a cysteine residue in the S6 or the S3 segment (KCNQ1C331A and KCNQ1C214A, respectively) were expressed in Xenopus laevis oocytes. A sustained current decrease was observed in KCNQ1wt and KCNQ1C331A, but not in KCNQ1C214A-injected oocytes. The analysis of tail currents, I/V curves and activation kinetics revealed a complex effect of TMS on the gating of KCNQ1wt and KCNQ1C331A. In another series we investigated the effect of TMS on IKs. TMS increased IKs of KCNQ1C214A/KCNE1-injected oocytes significantly less than IKs in KCNQ1wt/KCNE1- or KCNQ1C331A/KCNE1-injected cells. These results suggest that thimerosal interacts with the cysteine residue C214 in the S3 segment of KCNQ1, leading to a change of its gating properties. Our results support the idea that not only the inner shell, but also the outer shell of the channel is important for the gating behavior of voltage dependent K+ channels.”

“OBJECTIVES:

A cross sectional survey of dentists in the west of Scotland and unmatched controls was conducted to find the effect of chronic exposure to mercury on health and cognitive functioning.

METHODS:

180 dentists were asked to complete a questionnaire that included items on handling of amalgam, symptoms experienced, possible influences on psychomotor function, and the 12 item general health questionnaire. Dentists were asked to complete a dental chart of their own mouths and to give samples of urine, hair, and nails for mercury analysis. Environmental measurements of mercury in dentists’ surgeries were made and participants undertook a package of computerised psychomotor tests. 180 control subjects underwent a similar procedure, completing a questionnaire, having their amalgam surfaces counted, giving urine, hair, and nail samples and undergoing the psychomotor test package.

RESULTS:

Dentists had, on average, urinary mercury concentrations over four times that of control subjects, but all but one dentist had urinary mercury below the Health and Safety Executive health guidance value. Dentists were significantly more likely than control subjects to have had disorders of the kidney and memory disturbance. These symptoms were not significantly associated with urinary mercury concentration. Differences were found between the psychomotor performance of dentists and controls after adjusting for age and sex, but there was no significant association between changes in psychomotor response and mercury concentrations in urine, hair, or nails.

CONCLUSIONS:

Several differences in health and cognitive functioning between dentists and controls were found. These differences could not be directly attributed to their exposure to mercury. However, as similar health effects are known to be associated with mercury exposure, it would be appropriate to consider a system of health surveillance of dental staff with particular emphasis on symptoms associated with mercury toxicity where there is evidence of high levels of exposure to environmental mercury.”

“In skeletal and cardiac muscle cells, specific isoforms of the Ryanodine receptor channels mediate Ca2+ release from the sarcoplasmic reticulum. These channels are highly susceptible to redox modifications, which regulate channel activity. In this work, we studied the effects of Ca2+ (endogenous agonist) and Mg2+ (endogenous inhibitor) on the kinetics of Ca2+ release from sarcoplasmic reticulum vesicles isolated from skeletal or cardiac mammalian muscle. Native skeletal vesicles exhibited maximal stimulation of release kinetics by 10-20 microM [Ca2+], whereas in native cardiac vesicles, maximal stimulation of release required only 1 microM [Ca2+]. In 10 microM [Ca2+], free [Mg2+] < 0.1 mM produced marked inhibition of release from skeletal vesicles but free [Mg2+] < or = 0.8 mM did not affect release from cardiac vesicles. Incubation of skeletal or cardiac vesicles with the oxidant thimerosal increased their susceptibility to stimulation by Ca2+ and decreased the inhibitory effect of Mg2+ in skeletal vesicles. Sulfhydryl-reducing agents fully reversed the effects of thimerosal. The endogenous redox species, glutathione disulfide and S-nitrosoglutathione, also stimulated release from skeletal sarcoplasmic reticulum vesicles. In 10 microM [Ca2+], 35S-nitrosoglutathione labeled a protein fraction enriched in release channels through S-glutathiolation. Free [Mg2+] 1 mM or decreasing free [Ca2+] to the nM range prevented this reaction. Possible physiological and pathological consequences of redox modification of release channels on Ca2+ signaling in heart and muscle cells are discussed.”

“BACKGROUND:

Concern has been voiced about exposure to mercury (Hg) from dental amalgam fillings, and there is a need to assess whether this leads to signs of nephrotoxicity.

METHODS:

A total of 101 healthy adults (80 males and 21 females) were included in this study. The population as grouped into those having amalgam fillings (39 males and 10 females) and those without (41 males and 11 females). Hg was determined in blood, urine, hair and nails to assess exposure. Urinary excretion of beta2-microglobulin (beta2M), N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyltransferase (gammaGT) and alkaline phosphatase (ALP) were determined as markers of tubular damage. Albuminuria was assayed as an early indicator of glomerular dysfunction. Serum creatinine, beta2M and blood urea nitrogen (BUN) were determined to assess glomerular filtration.

RESULTS:

Hg levels in blood and urine were significantly higher in persons with dental amalgam than those without; in the dental amalgam group, blood and urine levels of Hg significantly correlated with the number of amalgams. Urinary excretion of NAG, gammaGT and albumin was significantly higher in persons with dental amalgam than those without. In the amalgam group, urinary excretion of NAG and albumin significantly correlated with the number of fillings. Albuminuria significantly correlated with blood and urine Hg.

CONCLUSION:

From the nephrotoxicity point of view, dental amalgam is an unsuitable filling material, as it may give rise to Hg toxicity. Hg levels in blood and urine are good markers of such toxicity. In these exposure conditions, renal damage is possible and may be assessed by urinary excretions of albumin, NAG, and gamma-GT.”

“Mercury levels measured in urine, hair, and saliva of 245 German children (8-10 years old) are reported. Mercury concentrations in urine ranged between <0.1 and 5.3 microg/l [geometric mean (GM) 0.26 microg/l or 0.25 microg/g creatinine; median for both, 0.22 in microg/l and microg/g, respectively]. Using multiple linear regression analysis, two predictors have been found accounting for 25.3% of the variance of mercury levels in urine: the number of teeth with amalgam fillings (23.2%) and the number of defective amalgam fillings (2.1%). The mercury content in hair ranged from <0.06 to 1.7 microg/g (GM 0.18 microg/g; median 0.18 microg/g). The frequency of fish consumption, the smoking habits of the parents, and the age of the children accounted for 20.4% of the variance of mercury levels in hair. The correlation between the hair mercury content and urine mercury concentration was low (r=0.297). Mercury levels in saliva ranged between <0.32 and 4.5 microg/l (median 0.16 microg/l). The mercury concentration in saliva was below the limit of quantification of 0.32 microg/l in more than 70% of the samples. Mercury analysis in urine is suitable to estimate mercury exposure due to amalgam fillings, whereas hair mercury better reflects mercury intake by fish consumption. Up to now, saliva does not seem to be a suitable tool to monitor the mercury burden, at least not at low exposure levels.”

“In 2001, the Maine State Legislature passed a law telling the Maine Bureau of Health to make a brochure about the advantages and disadvantages to human health and the environment of using mercury amalgam fillings in dental work. The same kind of information is included for other filling materials, to help patients in choosing what will be best for them.”

“Amalgam has been widely utilized to restore posterior teeth in pediatric dentistry, and is still taught as the material of choice for Class I and Class II restorations in many dental schools in the United States and Canada. Results of clinical trials are difficult to compare due to their heterogenicity, mainly due to differences in caries risk, operator skills, study duration, or patients’ age. Thus, the different studies report failure rates of amalgams ranging from 12% to over 70%. Treatment of caries should meet the needs of each particular patient, based on his/her caries risk. In general, for small occlusal lesions, a conservative preventive resin restoration, using composite or compomer in conjunction with sealant, would be more appropriate than the classic Class I amalgam preparation. For proximal lesions, amalgam would be indicated for 2-surface Class II preparations that do not extend beyond the line angles of primary teeth. This recommendation might not be appropriate for high-risk patients or for restoring first primary molars in children 4 years of age and younger where stainless steel crowns have demonstrated better longevity. Currently, amalgam demonstrates the best clinical success for Class II restorations that extend beyond the proximal line angles of permanent molars.”

Platelet-rich fibrin (PRF) therapy has been widely applied in regenerative dentistry, and PRF preparation has been optimized to efficiently form fibrin clots using plain glass tubes. Currently, a shortage of commercially available glass tubes has forced PRF users to utilize silica-coated plastic tubes. However, most plastic tubes are approved by regulatory authorities only for diagnostic use and remain to be approved for PRF therapy. To clarify this issue, we quantified silica microparticles incorporated into the PRF matrix. Blood samples were collected into three different brands of silica-containing plastic tubes and were immediately centrifuged following the protocol for advanced-PRF (A-PRF). Advanced-PRF-like matrices were examined using a scanning electron microscope (SEM), and silica microparticles were quantified using a spectrophotometer. Each brand used silica microparticles of specific size and appearance. Regardless of tube brands and individual donors, significant, but not accidental, levels of silica microparticles were found to be incorporated into the A-PRF-like matrix, which will be consequently incorporated into the implantation sites. Presently, from the increasing data for cytotoxicity of amorphous silica, we cannot exclude the possibility that such A-PRF-like matrices negatively influence tissue regeneration through induction of inflammation. Further investigation should be performed to clarify such potential risks.

“The role of estrogen as a neurotrophic/neuroprotective agent in neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases is increasingly being shown. In this study we examine the neuroprotective effects of β-estradiol on SHSY5Y neuroblastoma cells which have been exposed to the heavy metals cobalt and mercury. The results show that cobalt and mercury are able to induce oxidative stress and cell cytotoxicity and increase the secretion of β-amyloid 1–40 and 1–42. These deleterious effects are reversed by the pretreatment of cells with β-estradiol. It is further shown that β-estradiol exerts its neuroprotective action through mechanisms which reduce oxidative stress and reduce β-amyloid secretion. Pre-treatment of the cells with α-estradiol did not alleviate the toxic effects of the heavy metals.

Our results are significant as they contribute to a better understanding of the mode of action of estrogen with relevance to its use in the treatment of neurodegenerative disorders.”