Toxic Effects of Mercury on the Cardiovascular and Central Nervous Systems

Environmental contamination has exposed humans to various metal agents, including mercury. This exposure is more common than expected, and the health consequences of such exposure remain unclear. For many years, mercury was used in a wide variety of human activities, and now, exposure to this metal from both natural and artificial sources is significantly increasing. Many studies show that high exposure to mercury induces changes in the central nervous system, potentially resulting in irritability, fatigue, behavioral changes, tremors, headaches, hearing and cognitive loss, dysarthria, incoordination, hallucinations, and death. In the cardiovascular system, mercury induces hypertension in humans and animals that has wide-ranging consequences, including alterations in endothelial function. The results described in this paper indicate that mercury exposure, even at low doses, affects endothelial and cardiovascular function. As a result, the reference values defining the limits for the absence of danger should be reduced. History More than 2500 A.C., the prehistoric man used the cinabrio (mercury sulfide), due to its red-gold color, to draw on cave walls and perform face painting. Subsequently, mercury has been used in the amalgamation (direct burning of metallic mercury on the gravel, promoting the separation of gold), in photography and as an antiseptic in the treatment of syphilis Exposure to mercury brought harmful effects to health of humans, but changes resulting from human exposure to mercury only called the attention of the scientific society after the accidents in Japan and Iraq Mercury Characteristics Mercury is characterized as a highly malleable liquid at normal temperature and pressure Inorganic Mercury Compounds Elemental Mercury or Metalic Mercury Compounds. In its liquid form, the elemental mercury (Hg 0 ) is poorly absorbed and presents little health risk. However, in the vapor form, metallic mercury is readily absorbed through the lungs and can produce body damage Elemental mercury is used in thermometers and sphygmomanometers because of its uniform volumetric expansion, high surface tension, and lack of vitreous adherence to surfaces. Low electrical resistance and high thermal conductivity allow metallic mercury to be used in electrical and electronic materials. Because of its high oxidation power, metallic mercury is used in electrochemical operations in the chlorine and soda industries. Metallic mercury is also used in metallurgy, mining, and dentistry because of the easy amalgam formation with other metals. In addition, gold extraction with archaic and dangerous methods predispose miners to mercury poisoning. The burning of metallic mercury on the gravel promotes the separation of gold, a process called amalgamation, which causes emission of large amounts of mercury vapor that is inhaled immediately by the miner, since they do not use appropriate personal protective equipment Mercurous Mercury and Mercuric Mercury Compounds. The mercurous mercury in the form of mercurous chloride (Hg 2 Cl 2 ) is little absorbed in the body. It is believed that in the body the form of metallic mercury is changed to elemental mercury and mercuric mercury Mercuric mercury compounds, such as mercury salts, result from the combination of mercury with chlorine, sulfur, or oxygen. Mercuric mercury can be found in different states when combined with other chemical elements, including mercuric chloride (HgCl 2 ), which is highly toxic and corrosive; mercury sulfide (HgS), which is often used as a pigment in paints due to its red color; mercury fulminate (Hg(CNO) 2 ), which is used as an explosive detonator In the cardiovascular system, acute inorganic mercury exposition in vivo promotes reduction of myocardial force development Organic Mercury. Organic mercury compounds, also called organometallic, result from a covalent bond between mercury and the carbon [8] atom of an organic functional group such as a methyl, ethyl, or phenyl group. Methylmercury (CH 3 Hg + ) is by far the most common form of organic Hg to which humans and animals are exposed. CH 3 Hg + in the environment is predominantly formed by methylation of inorganic mercuric ions by microorganisms present in soil and water Journal of Biomedicine and Biotechnology 3 The organomercury antiseptics still used are Merthiolate, Bacteran, and Thimerosal [40]. Thimerosal is an organomercurial compound that since 1930 has been widely used as a preservative in biological material such as vaccines and serums used to prevent microbiological growth Forms of Mercury Exposure Mercury is now considered an environmental pollutant of high risk to public health because of its high toxicity and mobility in ecosystems More natural sources of mercury include volcanic activity, earthquakes, erosion, and the volatilization of mercury present in the marine environment and vegetation Mercury contaminates the environment through a cycle involving the initial emission, the subsequent atmospheric circulation of the vapor form, and the eventual return of mercury to the land and water via precipitation ( Mercury present in seas and rivers after methylation can contaminate fish Transport and Elimination of Mercury Inhaled elemental mercury vapor, for example, is readily absorbed through mucous membranes and the lung and is rapidly oxidized but not as quickly as to prevent the deposition of considerable amount in the brain Then, toxicity for man varies depending on the form of mercury, dose, and rate of exposure. The target organ for inhalted mercury vapor is primarily the brain Oxidized mercury binds strongly to SH groups; this reaction can inactivate enzymes, lead to tissue damage and interfere with various metabolic processes Doses of Mercury and Safety Legislation The chemical form of mercury in the air affects its time of permanence and its dispersion in the atmosphere. The elemental mercury form can persist for more than four years in the air, while its compounds are deposited in a short time at locations near their origin. In the northern hemisphere, their average concentration in the atmosphere is estimated at 2 ng/m 3 and in the southern hemisphere is less than 1 ng/m 3 . In urban areas, there is a great variability of these concentrations being found up to 67 ng/m 3 with a mean of 11 ng/m 3 in Japan In 2004, the Joint FAO (Food and Agriculture Organization of the United National)/WHO Expert Committee on Food Additives (JECFA) established that the safe concentration of methylmercury intake, without the appearance of neurological disorders, is 1.6 mg/kg of body weight. However, in 2006, JECFA stated that this concentration is not safe for intrauterine exposure, because fetuses are more sensitive to the onset of neurological disorders after exposure to methylmercury Currently, the general population is exposed to mercury by the following main sources: the consumption of contaminated fish, the use and manipulation of dental amalgam, thimerosal contained in vaccines, workers in industries of chlorine, caustic soda, miners, and workers in industries of fluorescent lamps In Brazil, the rules for vaccination of the Ministry of Health, published in June 2001, shows that thimerosal is used in many vaccines. These vaccines prevent flu (influenza vaccine), rabies (rabies vaccine), infection with meningococcus serogroup b, and hepatitis B The US Environmental Protection Agency's recommended a reference blood concentration of mercury to be 5.8 ng/mL; concentrations below this level are considered to be safe In the following sections, we will describe results obtained from animals with chronic and acute exposure to mercury. Some of these studies were performed with mercury exposure protocols that led to blood concentrations slightly above the reference values. Nevertheless, these concentrations could be easily found in exposed populations and may even be considered low when compared with concentrations in humans who consume large amounts of fish or who live in areas contaminated with mercury. Effect of Mercury on the Central Nervous System (CNS) Among the compounds of mercury, the methylmercury is primarily responsible for the neurological alterations present in humans and experimental animals. It is believed that the mechanisms are related to the toxic increase in reactive oxygen species (ROS). Oxidative stress is associated with the etiology of neurodegenerative diseases such as amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease Reinforcing the hypothesis that the majority of injuries caused by methylmercury (MeHg) in the central nervous system are related to its ability to increase reactive oxygen species, Studies also demonstrate that mercury has the ability to reduce the number of neuron and cytoarchitecture in individuals with prenatal exposure to mercury In addition, because of its high affinity for sulfhydryl groups in tubulin, methylmercury inhibits the organization of microtubules that are important in CNS development Corroborating these findings, the study conducted by Halbach et al. [90] studied a correlation in Iraqi children between the level of maternal exposure to methylmercury during pregnancy and psychomotor retardation. SandborghEnglund et al. Effect of Mercury on the Cardiovascular System For decades, the toxic effects of mercury were associated mainly with the central nervous system; however, inorganic mercury also produces profound cardiotoxicity The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. Exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction The reduction in glutathione peroxidase with seleniumdependent activity is the result of the decreased bioavailability of selenium, a molecule that is required for enzymatic activity Cardiovascular changes resulting from mercury poisoning are also described in animal models. However, the mechanism involved in the effects of mercury on the cardiovascular system is not fully understood but seems to be dependent on both the dose and time of exposure. Raymond and Ralston [123] studied the hemodynamic effects of an intravenous injection of HgCl 2 (5 mg/kg) in rats and observed that mercury produced cardiac diastolic failure and pulmonary hypertension. Moreover, Naganuma et al. Our group has found that chronic exposure to low doses of mercury (1st dose 4.6 μg/kg followed by 0.07 μg/kg/day for 30 days, im) attained a blood mercury concentration of approximately 8 ng/mL, a concentration similar to the levels found in exposed humans. This exposure produced a negative inotropic effect in perfused hearts, although increasing myosin ATPase activity. Invivo, arterial or ventricular pressures did not change The chronic exposure to low concentrations of mercury was also able to induce endothelial dysfunction in resistance and conductance vessels, most likely because of the decreased nitric oxide (NO) bioavailability due to the increased superoxide anion (O 2 •− ) production from NADPH oxidase Taken together, these data show that chronic low doses of mercury have an important and deleterious effect on vascular function by reducing NO bioavailability. The degree of severity of mercury exposure is comparable to traditional cardiovascular risk factors, such as hypertension diabetes or hypercholesterolemia. Therefore, mercury could be considered an important risk factor for cardiovascular disease that could play a role in the development of cardiovascular events. The association between mercury exposure and an increased risk of developing cardiovascular and neurological diseases is apparent. Thus, continuous exposure to mercury can be dangerous, and current reference values, once considered to be without risk, should be reevaluated and reduced

Soybean oil increases SERCA2a expression and left ventricular contractility in rats without change in arterial blood pressure

<p>Abstract</p> <p>Background</p> <p>Our aim was to evaluate the effects of soybean oil treatment for 15 days on arterial and ventricular pressure, myocardial mechanics and proteins involved in calcium handling.</p> <p>Methods</p> <p>Wistar rats were divided in two groups receiving 100 μL of soybean oil (SB) or saline (CT) i.m. for 15 days. Ventricular performance was analyzed in male 12-weeks old Wistar rats by measuring left ventricle diastolic and systolic pressure in isolated perfused hearts according to the Langendorff technique. Protein expression was measured by Western blot analysis.</p> <p>Results</p> <p>Systolic and diastolic arterial pressures did not differ between CT and SB rats. However, heart rate was reduced in the SB group. In the perfused hearts, left ventricular isovolumetric systolic pressure was higher in the SB hearts. The inotropic response to extracellular Ca²⁺and isoproterenol was higher in the soybean-treated animals than in the control group. Myosin ATPase and Na⁺-K⁺ATPase activities, the expression of sarcoplasmic reticulum calcium pump (SERCA2a) and sodium calcium exchanger (NCX) were increased in the SB group. Although the phosfolamban (PLB) expression did not change, its phosphorylation at Ser¹⁶was reduced while the SERCA2a/PLB ratio was increased.</p> <p>Conclusions</p> <p>In summary, soybean treatment for 15 days in rats increases the left ventricular performance without affecting arterial blood pressure. These changes might be associated with an increase in the myosin ATPase activity and SERCA2a expression.</p

Síndrome de Parsonage-Turner: relato de caso em paciente HIV soropositivo Parsonage-Turner Syndrome: case report of a HIV seropositive patient

A síndrome de Parsonage-Turner é uma doença rara que acomete a musculatura da cintura escapular levando à hipotrofia muscular e grande déficit motor. A etiologia é indeterminada; acredita-se que existam fatores infecciosos e autoimunes envolvidos. O diagnóstico é de exceção, e os principais diagnósticos diferenciais são hérnias discais cervicais, lesões do manguito rotador e doenças reumáticas. Na investigação diagnóstica realizamos exames laboratoriais, radiografias e ressonância magnética dos ombros e da coluna cervical com destaque para a eletroneuromiografia auxiliando no diagnóstico definitivo. Por se tratar de uma doença raramente associada à soropositividade do vírus HIV e pela importância do diagnóstico precoce para o melhor tratamento destes pacientes é que relatamos este caso.<br>The Parsonage-Turner Syndrome is a rare disease that affects the muscles of the scapular girdle, leading to muscular atrophy and a large motor deficit. The etiology is unknown, but it is believed that infectious and autoimmune factors are involved. The diagnosis is made by exclusion, and the main differential diagnoses are cervical disc hernias, rotator cuff injuries and rheumatic diseases. During diagnostic research, we conducted laboratory tests, radiographs and MRI of the shoulder and cervical spine, with particular reference to electroneuromyography to help generate a definitive diagnosis. This case report is presented because it shows a disease that is rarely associated with HIV seropositivity and the importance of early diagnosis for better treatment of these patients

Densidade mineral óssea estimada pelo Osteorisk em pacientes com escoliose idiopática do adolescente Bone mineral density estimated by Osteorisk in patients with adolescent idiopathic scoliosis

OBJETIVO: Considera-se a prevalência de osteoporose em portadores de Escoliose Idiopática do Adolescente (EIA) maior do que na população adolescente em geral.Uma alternativa à radiologia para caracterização da densidade mineral óssea pode ser através de índices correlativos, como o Osteorisk, de fácil acesso e baixo custo, que auxilia o médico na solicitação da Densitometria Óssea. Por considerarmos que a osteoporose pode interferir na evolução e no tratamento da EIA fomos motivados a realizar este estudo. Nosso objetivo foi avaliar subjetivamente a densidade mineral óssea através do índice Osteorisk em pacientes portadores de EIA. MÉTODOS: Foram avaliados pacientes saudáveis, (grupo controle, n=30) e pacientes com EIA (n=30), dos quais obtivemos idade, peso e altura, sendo estabelecido o Osteorisk. Feito teste t de Student não-pareado, com pOBJECTIVE: The prevalence of osteoporosis in patients with Adolescent Idiopathic Scoliosis (AIS) is believed to be higher than in the general adolescent population. An alternative to radiology for the characterization of bone mineral density may be through correlative indexes like the Osteorisk index, which is easy to access and low in cost, and which helps the doctor in the request for Bone Densitometry. Our belief that osteoporosis can affect the evolution and treatment of AIS was what motivated us to conduct this study. Our objective was to subjectively evaluate bone mineral density by the Osteorisk index in patients with AIS. METHODS: Healthy patients (control group, n=30) and patients with AIS (n = 30) were evaluated, documenting age, weight and height, and establishing the Osteorisk. The unpaired Student t test was performed, with a level of significance of p <0.05. RESULTS: The mean Osteorisk found for the patients with AIS was 6.38 ± 2.2 while in the control group, it was 8.27 ± 2.14, which represents a low risk of developing osteoporosis in both groups. Comparing these means between the groups, a lower Osteorisk was observed in the AIS group. CONCLUSION: Our study showed that there is low risk of developing osteoporosis in patients with AIS. Level of Evidence I, prospective study