Chronic Mercury Research Articles

Inorganic mercury exposure in prairie voles (Microtus ochrogaster) alters the expression of toll-like receptor 4 and activates inflammatory pathways in the liver in a sex-specific manner

Environmental exposure to mercury can cause a number of adverse effects in humans including the disruption of endocrine function that may result in sex-specific effects. The present study was designed to characterize sex-specific effects of chronic inorganic mercury exposure on toll-like receptor (TLR) 2 and TLR4 and inflammatory signaling in the liver of prairie voles (Microtus ochrogaster). Following 10 weeks of exposure to mercury via drinking water, effects on protein expression levels of TLR2 and TLR4 and the downstream p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa (NF-κB) signaling pathways were assessed. Using immunoblot analysis, we found that mercury exposure significantly enhanced the expression of TLR4 and activated p38 MAPK and NF-κB pathways in vole livers. This is the first report indicating that TLR4 may serve as a sensor for chronic mercury exposure in the liver. Further, compared to females, mercury-treated male voles exhibited significant increases in activated p38 MAPK and a greater extent of liver damage. Together, these findings establish sex-specific liver immunomodulation and cellular signaling following chronic inorganic mercury exposure. Furthermore, this study also supports the use of voles as biomarkers of environmental mercury contamination and offers a promising in vivo tool to test various therapeutic strategies for mercury detoxification.

Application of the national diagnostic criteria of occupational mercury poisoning

To investigate the clinical manifestation of patients with renal injury induced by chronic mercury intoxication and the application of the diagnostic criteria of occupational mercury poisoning. The clinical data of 8 patients with chronic occupational mercury intoxication were analysed and evaluated. All the observed clinical signs of chronic mercury intoxication correspond with the items of the diagnostic criteria of occupational mercury poisoning. The increasing beta2-MG was one of the clinical manifestations of renal injury induced by chronical mercury intoxication. The renal injury obviously was dose-dependent and reversible. The national diagnostic criteria of occupational mercury poisoning is practically valuable. The renal injury induced by chronic mercury intoxication should not be neglected.

Lessons learned from a fatal case of mercury intoxication

While many cases of metallic mercury poisoning have been reported, cases of metallic mercury poisoning from multiple exposure routes are rare. We report the case of a 36-year-old Latin American male who presented with rash, sore throat, fever, chills, cough, and diarrhea after chronic mercury vapor exposure and likely intravenous injection. Despite chelation treatment with meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropanesulfonic acid (DMPS), the patient's clinical course was complicated by renal failure and he passed away after 18 days. The most striking aspect of this case is that despite use of chelators, a dramatic increase in blood mercury level occurred. We discuss the rationale for combined use of chelators with hemodialysis and other treatments such as plasma exchange in the setting of acute mercury poisoning. This case also illustrated the potentially serious side effects of the chelation drug DMSA, and we discuss the potential relevance of dosing frequency to the occurrence rates of such side effects. Despite the tragic outcome, on review of case literature, we believe this case provides valuable lessons concerning the use of DMSA and DMPS to treat mercury toxicity, particularly with regard to the combined use of chelation agents and hemodialysis.

Heavy metal poisoning and cardiovascular disease.

Cardiovascular disease (CVD) is an increasing world health problem. Traditional risk factors fail to account for all deaths from CVD. It is mainly the environmental, dietary and lifestyle behavioral factors that are the control keys in the progress of this disease. The potential association between chronic heavy metal exposure, like arsenic, lead, cadmium, mercury, and CVD has been less well defined. The mechanism through which heavy metals act to increase cardiovascular risk factors may act still remains unknown, although impaired antioxidants metabolism and oxidative stress may play a role. However, the exact mechanism of CVD induced by heavy metals deserves further investigation either through animal experiments or through molecular and cellular studies. Furthermore, large-scale prospective studies with follow up on general populations using appropriate biomarkers and cardiovascular endpoints might be recommended to identify the factors that predispose to heavy metals toxicity in CVD. In this review, we will give a brief summary of heavy metals homeostasis, followed by a description of the available evidence for their link with CVD and the proposed mechanisms of action by which their toxic effects might be explained. Finally, suspected interactions between genetic, nutritional and environmental factors are discussed.

Serum Biochemical Change Induced by In Vitro Sub chronic Mercury Chloride in Yellowfin Sea Bream (Acanthopagrus latus)

Serum Biochemical Change Induced by In Vitro Sub chronic Mercury Chloride in Yellowfin Sea Bream (Acanthopagrus latus)

Persistence of EDHF pathway and impairment of the nitric oxide pathway after chronic mercury chloride exposure in rats: Mechanisms of endothelial dysfunction

Chronic mercury exposure impairs vascular function, leading to the depression of endothelium-dependent vasodilatation. Loss of the nitric oxide (NO) pathway has been implicated, but little is known about effects on other endothelial mediators. This study investigated the mechanisms of endothelial dysfunction in rats subjected to chronic mercury chloride exposure. The endothelium-dependent relaxation of rat aorta evoked by acetylcholine (ACh) and isoproterenol was impaired in a dose-dependent manner by chronic mercury chloride exposure. Endothelium-independent responses to sodium nitroprusside (SNP) were not affected by chronic mercury chloride exposure. In healthy vessels, ACh-induced relaxation was inhibited by L-N-nitroarginine methyl ester (L-NAME; 10(-4) M) and partially by glybenclamide (10(-5) M), indicating the involvement of NO and endothelium-derived hyperpolarizing factor (EDHF). In vessels from mercury-exposed rats, responses to ACh were insensitive to L-NAME but were significantly reduced by glybenclamide, indicating selective loss of NO-mediated relaxation. In vessels from mercury-exposed rats, responses to ACh were partially restored after treatment with the antioxidant, superoxide dismutase (SOD) and catalase, this effect was not seen when aorta from exposed group was incubated with L-NAME along with SOD and catalase indicating selective loss of NO-mediated vasodilatation and with no affect the EDHF-mediated component of relaxation. The results imply that chronic mercury exposure selectively impairs the NO pathway as a consequence of oxidative stress, while EDHF is able to maintain endothelium-dependent relaxation at a reduced level.

The Dawn of Drug Safety

Clinical pharmacologists have a great deal to learn from Myles Stephens's panoramic view of drug safety, even though he confines himself largely to events prior to McBride's Lancet letter of 16th December 1961 that described ‘multiple severe abnormalities in babies delivered of women who were given the drug thalidomide (Distival) during pregnancy’. The author protests that his is ‘not a history book.’ This is contradicted by the first eight chapters, which run in chronological order from 80 000 BC to 1961, listing a host of facts, and providing a rich store of quotations. There is Hippocrates's advice to ‘leave your drug in the chemist's pot if you can heal the patient with food’ (370 BC). We learn of the seven categories of potential drug–drug interaction listed in a Chinese herbal of the 2nd century AD, which also notes that with chronic mercury ingestion ‘you will become a celestial being.’ Sir Samuel Garth (1699) observes that ‘Death in ambush lay in ev'ry pill’ and Dr Frances Kelsey describes how, a week after beginning her career as a reviewing officer at the US Food & Drug Administration, she was assigned the task of considering the new drug application for thalidomide. The chronology is a tour de force, but it often wanders from drug safety. For example, a substantial section deals with the consequences of syphilis and the cures proposed for it. Dr Stephens points out that the first general account of adverse drug reactions, an obscure French thesis, was not published until 1862, and that the first major work was Louis Lewin's textbook from 1881. It could be argued that the reader might have been spared a great deal of herbal lore and a fairly extensive treatise on venereology, although I for one enjoyed learning that ‘pudendagra’ was a synonym for syphilis. Stephens dissects in a second section the adverse reactions to six marker drugs, Veratrum spp., Hyoscyamus niger, mercury compounds, opiates, aspirin and streptomycin. The most impressive finding for the first four of these is how many of the adverse effects recorded in the 2007 edition of Myler's Side Effects of Drugs had already been listed in Lewin's textbook. The well-referenced sections on aspirin and streptomycin are fascinating. There is a remarkable account by Geogre Orwell of his adverse reaction to streptomycin treatment for tuberculosis, affecting his skin, nails, hair and mucous membranes. Dr Stephens, author of the textbook on the detection of adverse drug reactions, allows his readers to make their own deductions about this (surely Stevens-Johnson syndrome) and much else. An anecdote of a painter with palsies and colic is said to represent mercury poisoning, although lead poisoning seems more probable. The carefully tabulated relationship between salicylate concentration and toxic effects is at best contestable. The book brings together much that must have taken a life-time in pharmacovigilance to learn. It will be a valuable reference source. The author apologizes for his ‘inept proof-reading’ and when it is reprinted there will be the opportunity to remove the ‘imminent physicians,’ to correct ‘schlerosing,’ and to decide which system of transliteration from Chinese will be best.

Mercury Exposure and Children's Health

Acute or chronic mercury exposure can cause adverse effects during any period of development. Mercury is a highly toxic element; there is no known safe level of exposure. Ideally, neither children nor adults should have any mercury in their bodies because it provides no physiological benefit. Prenatal and postnatal mercury exposures occur frequently in many different ways. Pediatricians, nurses, and other health care providers should understand the scope of mercury exposures and health problems among children and be prepared to handle mercury exposures in medical practice. Prevention is the key to reducing mercury poisoning. Mercury exists in different chemical forms: elemental (or metallic), inorganic, and organic (methylmercury and ethyl mercury). Mercury exposure can cause acute and chronic intoxication at low levels of exposure. Mercury is neuro-, nephro-, and immunotoxic. The development of the child in utero and early in life is at particular risk. Mercury is ubiquitous and persistent. Mercury is a global pollutant, bio-accumulating, mainly through the aquatic food chain, resulting in a serious health hazard for children. This article provides an extensive review of mercury exposure and children's health.

Intoxication par le mercure

Mercury is a widespread heavy metal with potential severe impacts on human health. Exposure conditions to mercury and profile of toxicity among humans depend on the chemical forms of the mercury: elemental or metallic mercury, inorganic or organic mercury compounds. This article aims to reviewing and synthesizing the main knowledge of the mercury toxicity and its organic compounds that clinicians should know. Acute inhalation of metallic or inorganic mercury vapours mainly induces pulmonary diseases, whereas chronic inhalation rather induces neurological or renal disorders (encephalopathy and interstitial or glomerular nephritis) . Methylmercury poisonings from intoxicated food occurred among some populations resulting in neurological disorders and developmental troubles for children exposed in utero. Treatment using chelating agents is recommended in case of symptomatic acute mercury intoxication; sometimes it improves the clinical effects of chronic mercury poisoning. Although it is currently rare to encounter situations of severe intoxication, efforts remain necessary to decrease the mercury concentration in the environment and to reduce risk on human health due to low level exposure (dental amalgam, fish contamination by organic mercury compounds…). In case of occupational exposure to mercury and its compounds, some disorders could be compensated in France. Clinicians should work with toxicologists for the diagnosis and treatment of mercury intoxication.

Using of the biofeedback in rehabilitation of patients with mercury intoxication

The study results of using the biological reverse connection training with the musical therapy in the rehabilitation of the patients with the chronic mercury intoxication are represented in this paper. The positive effect of the BRC-training on processes concentration of retention, some subscales of the life quality, the functional state of the central afferent conducting structures as well as the neurophysiologic balance of the bioelectrical brain activity have been indicated.

Furthering the evidence on the use of mercury in dental amalgam fillings

Eyeson J, House I, Yang YH, Warnakulasuriya KA (2010) Relationship between mercury levels in blood and urine and complaints of chronic mercury toxicity from amalgam restorations. Br Dent J 208(4): E7; discussion 162-3

Relationship between mercury levels in blood and urine and complaints of chronic mercury toxicity from amalgam restorations

Aim To determine whether patients complaining of oral and medical symptoms perceived to be associated with chronic mercury toxicity have elevated mercury levels in their blood and urine. Methods The study group in this audit were 56 patients presenting to an oral medicine unit with complaints perceived to be related to chronic mercury toxicity. Their symptoms and co-morbidity were charted and mercury levels in blood and urine were biochemically tested by atomic absorption spectrophotometry. Results None had elevated mercury levels in blood or urine above the normal threshold level. Subgroup analysis showed subjects with oral lesions, autoimmune disorders and multiple sclerosis had relatively and significantly higher mercury levels within this cohort, but within the threshold values. When tested by multiple logistic regression adjusted for age and gender, mercury levels in blood or urine, numbers of amalgams were not significant for multiple sclerosis or previously diagnosed autoimmune disease. Conclusion Mercury levels in blood and urine of this cohort of patients with perceived chronic mercury toxicity were within the normal range in accordance with a national laboratory threshold value.

Antioxidative responses and bioaccumulation in Japanese flounder larvae and juveniles under chronic mercury exposure

This study investigated the sub-lethal effects of waterborne mercury on growth, bioaccumulation and antioxidative responses of larvae and juveniles of Japanese flounder ( Paralichthys olivaceus). Fish were exposed to 0–10 μg Hg 2 + L − 1 solutions from embryonic to the juvenile stages for 80 days. Antioxidative responses to mercury exposure were studied in metamorphosing larvae (18 days post hatching, dph), settling larvae (33 dph) and juveniles (78 dph). Results showed that increasing mercury concentration led to increased mercury bioaccumulation and reduced flounder growth. Of the antioxidants investigated, superoxide dismutase (SOD) and catalase (CAT) activities at the three developmental stages were sensitive to mercury exposure and increased with increasing mercury concentration. Glutathione (GSH) content was elevated in metamorphosing larvae, but decreased in juveniles as mercury concentration increased. Glutathione- S-transferase (GST) activity did not significantly vary with mercury concentration in either larvae or juveniles. Mercury exposure did not affect malondialdehyde (MDA) content of larvae, but significantly increased MDA content of juveniles. Results suggest that flounder larvae and juveniles have the potential to manipulate the levels of antioxidants such as SOD, CAT and GSH, which protect flounder from oxidative stress induced by mercury exposure. These antioxidants could serve as biomarkers of mercury contamination in the aquatic environment.

Relationship between mercury levels in blood and urine and complaints of chronic mercury toxicity from amalgam restorations

To determine whether patients complaining of oral and medical symptoms perceived to be associated with chronic mercury toxicity have elevated mercury levels in their blood and urine. The study group in this audit were 56 patients presenting to an oral medicine unit with complaints perceived to be related to chronic mercury toxicity. Their symptoms and co-morbidity were charted and mercury levels in blood and urine were biochemically tested by atomic absorption spectrophotometry. None had elevated mercury levels in blood or urine above the normal threshold level. Subgroup analysis showed subjects with oral lesions, autoimmune disorders and multiple sclerosis had relatively and significantly higher mercury levels within this cohort, but within the threshold values. When tested by multiple logistic regression adjusted for age and gender, mercury levels in blood or urine, numbers of amalgams were not significant for multiple sclerosis or previously diagnosed autoimmune disease. Mercury levels in blood and urine of this cohort of patients with perceived chronic mercury toxicity were within the normal range in accordance with a national laboratory threshold value.

Summary of: Relationship between mercury levels in blood and urine and complaints of chronic mercury toxicity from amalgam restorations

Aim To determine whether patients complaining of oral and medical symptoms perceived to be associated with chronic mercury toxicity have elevated mercury levels in their blood and urine. Methods The study group in this audit were 56 patients presenting to an oral medicine unit with complaints perceived to be related to chronic mercury toxicity. Their symptoms and co-morbidity were charted and mercury levels in blood and urine were biochemically tested by atomic absorption spectrophotometry. Results None had elevated mercury levels in blood or urine above the normal threshold level. Subgroup analysis showed subjects with oral lesions, autoimmune disorders and multiple sclerosis had relatively and significantly higher mercury levels within this cohort, but within the threshold values. When tested by multiple logistic regression adjusted for age and gender, mercury levels in blood or urine, numbers of amalgams were not significant for multiple sclerosis or previously diagnosed autoimmune disease. Conclusion Mercury levels in blood and urine of this cohort of patients with perceived chronic mercury toxicity were within the normal range in accordance with a national laboratory threshold value.

Chronic mercury poisoning: Report of two siblings

Mercury exists as organic inorganic and elementary forms in nature and is one of the most toxic metals that are poisonous for human beings. Mercury is commonly used in many different sectors of industry such as in insects formulas, agriculture products, lamps, batteries, paper, dyes, electrical/electronic devices, jewelry, and in dentistry. In this study, two siblings (one a 7-year-old boy and the other a 13 years old girl) are reported who developed chronic mercury poisoning as a result of long-term contact with batteries. Our aim is to emphasize the importance of mercury poisoning that is extremely rarely seen in childhood.

Mercury Exposure and Periodontitis Among a Korean Population: The Shiwha‐Banwol Environmental Health Study

The oral effect of chronic low-level mercury exposure is not completely understood. This study examined whether mercury exposure is associated with periodontitis. This study cross-sectionally surveyed 1,328 residents (598 males and 730 females) from the prospective Shiwha and Banwol cohort in Korea from July 2005 to August 2006 at baseline. Two dentists assessed periodontitis, an outcome, using the Community Periodontal Index (CPI): CPI 3 or 4 and CPI 0 to 2 were classified as periodontitis and non-periodontitis, respectively. The hair mercury level, the predictor, was analyzed. The mercury level was categorized according to the reference dose of the Environmental Protection Agency of the United States: normal = <1 ppm and high = > or =1 ppm. Age, gender, economic status, smoking, frequency of daily toothbrushing, diabetes mellitus, hyperlipidemia, and obesity were assessed as confounders. Logistic regression analysis was used to evaluate the adjusted association. Subgroup analyses for gender were also performed. Mercury exposure was independently associated with periodontitis (odds ratio = 3.17). Males with high mercury levels had a 50.0% higher probability of having periodontitis than females with normal mercury levels. Of them, the interaction effect between the body burden of mercury and gender was 39.0%. The odds ratio between periodontitis and high mercury levels was higher for males than females (95% confidence interval: 0.99 to 2.23 versus 0.59 to 1.26, respectively). These results suggest that mercury exposure had an independent association with periodontitis. High body-burden mercury in males might be a contributory factor linked with periodontitis.

P1.074 Frontotemporal dementia and parkinsonism in a patient with a chronic mercury intoxication

P1.074 Frontotemporal dementia and parkinsonism in a patient with a chronic mercury intoxication

Health assessment of artisanal gold miners in Indonesia

Small scale miners use mercury to extract gold from ore in many countries. An environmental and health assessment was performed in Indonesia in two regions, Galangan in Central Kalimantan and Talawaan in Northern Sulawesi. The environmental assessment showed severe mercury contamination of the sediments, and increased mercury levels in local fish. For the health investigation 281 volunteers were recruited and examined by a standardized questionnaire, a neurological examination and neuro-psychological tests. A medical score was used consisting of significant factors of mercury intoxication. Mercury exposed workers showed typical symptoms of mercury intoxication, such as movement disorders (ataxia, tremor, dysdiadochokinesia, etc.). Blood, urine and hair samples were taken from any participant and analyzed for mercury. The mercury concentration in the biomonitors was high, partly extreme high in the working population, increased in the population living in the same habitat and low in the control group. By a standard protocol which includes a combination of threshold values of mercury in the biomonitors and a medical sum score the diagnosis of chronic mercury intoxication was made for highly burdened workers (amalgam smelters) in 55% in Sulawesi and in 62% in Kalimantan. Less exposed mineral processors and the general population in the mining areas were also intoxicated to a high percentage.

Luteinizing hormone provides a causal mechanism for mercury associated disease

Previous studies have demonstrated that the pituitary is a main target for inorganic mercury (I-Hg) deposition and accumulation within the brain. My recent study of the US population (1999-2006) has uncovered a significant, inverse relationship between chronic mercury exposure and levels of luteinizing hormone (LH). This association with LH signifies more than its presumed role as bioindicator for pituitary neurosecretion and function. LH is the only hormone with a rare and well characterized, high affinity binding site for mercury. On its catalytic beta subunit, LH has the structure to preferentially bind inorganic mercury almost irreversibly, and, by that manner, accumulate the neurotoxic element. Thus, it is likely that LH is an early and significant target of chronic mercury exposure. Moreover, due to the role of LH in immune-modulation and neurogenesis, I present LH as a central candidate to elucidate a causal mechanism for chronic mercury exposure and associated disease.