Evaluation of the use of human hair for biomonitoring the deficiency of essential and exposure to toxic elements.

Monitoring the nutritional status of essential elements and assessing exposure of individuals to toxic elements is of great importance for human health. Thus, the appropriate selection and measurement of biomarkers of internal dose is of critical importance. Due to their many advantages, hair samples have been widely used to assess human exposure to different contaminants. However, the validity of this biomarker in evaluating the level of trace elements in the human body is debatable. In the present study, we evaluated the relationship between levels of trace elements in hair and whole blood or plasma in a Brazilian population. Hair, blood and plasma were collected from 280 adult volunteers for metal determination. An ICP-MS was used for sample analysis. Manganese, copper, lead and strontium levels in blood varied from 5.1 to 14.7, from 494.8 to 2383.8, from 5.9 to 330.1 and from 11.6 to 87.3 microg/L, respectively. Corresponding levels in hair varied from 0.05 to 6.71, from 0.02 to 37.59, from 0.02 to 30.63 and from 0.9 to 12.6 microg/g. Trace element levels in plasma varied from 0.07 to 8.62, from 118.2 to 1577.7 and from 2.31 to 34.2 microg/L for Mn, Cu and Sr, respectively. There was a weak correlation (r=0.22, p<0.001) between lead levels in hair and blood. Moreover, copper and strontium levels in blood correlate with those levels in plasma (r=0.64 , p<0.001 for Cu) and (r=0.22, p<0.05 for Sr). However, for Cu, Mn and Sr there was no correlation between levels in hair and blood. Our findings suggest that while the idea of measuring trace elements in hair is attractive, hair is not an appropriate biomarker for evaluating Cu, Mn and Sr deficiency or Pb exposure.

A common matrix metalloproteinase (MMP)-2 polymorphism affects plasma MMP-2 levels in subjects environmentally exposed to mercury.

Mercury (Hg) exposure is associated with disease conditions, including cardiovascular problems. Although the mechanisms implicated in these complications have not been precisely defined yet, matrix metalloproteinases (MMPs) may be involved. The gene encoding MMP-2 presents genetic polymorphisms which affect the expression and activity level of this enzyme. A common polymorphism of MMP-2 gene is the C(-1306)T (rs 243865), which is known to disrupt a Sp1-type promoter site (CCACC box), thus leading to lower promoter activity associated with the T allele. This study aimed at examining how this polymorphism affects the circulating MMP-2 levels and its endogenous inhibitor, the tissue inhibitor of metalloproteinase-2 (TIMP-2) in 210 subjects environmentally exposed to Hg. Total blood and plasma Hg concentrations were determined by inductively coupled plasma-mass spectrometry (ICP-MS). MMP-2 and TIMP-2 concentrations were measured in plasma samples by gelatin zymography and ELISA, respectively. Genotypes for the C(-1306)T polymorphism were determined by Taqman® Allele Discrimination assay. We found a positive association (p=0.0057) between plasma Hg concentrations and MMP-2/TIMP-2 (an index of net MMP-2 activity). The C(-1306)T polymorphism modified MMP-2 concentrations (p=0.0465) and MMP-2/TIMP-2 ratio (p=0.0060) in subjects exposed to Hg, with higher MMP-2 levels been found in subjects carrying the C allele. These findings suggest a significant interaction between the C(-1306)T polymorphism and Hg exposure, possibly increasing the risk of developing diseases in subjects with the C allele.

A functional matrix metalloproteinase (MMP)-9 polymorphism modifies plasma MMP-9 levels in subjects environmentally exposed to mercury.

Mercury (Hg) exposure causes health problems including cardiovascular diseases. Although precise mechanisms have not been precisely defined yet, matrix metalloproteinases (MMPs) may be involved. The gene encoding MMP-9 presents genetic polymorphisms which affect the expression and activity level of this enzyme. Two polymorphisms in the promoter region [C(-1562)T and (CA)(n)] are functionally relevant, and are implicated in several diseases. This study aimed at examining how these polymorphisms affect the circulating MMP-9 levels and its endogenous inhibitor, the tissue inhibitor of metalloproteinase-1 (TIMP-1) in 266 subjects environmentally exposed to Hg. Blood and plasma Hg concentrations were determined by inductively coupled plasma-mass spectrometry (ICP-MS). MMP-9 and TIMP-1 concentrations were measured in plasma samples by gelatin zymography and ELISA, respectively. Genotypes for the C(-1562)T and the microsatellite (CA)(n) polymorphisms were determined. We found a positive association (P<0.05) between plasma Hg concentrations and MMP-9/TIMP-1 ratio (an index of net MMP-9 activity). When the subjects were divided into tertiles with basis on their plasma Hg concentrations, we found that the (CA)(n) polymorphism modified MMP-9 concentrations and MMP-9/TIMP-1 ratio in subjects with the lowest Hg concentrations (first tertile), with the highest MMP-9 levels being found in subjects with genotypes including alleles with 21 or more CA repeats (H alleles) (P<0.05). Conversely, this polymorphism had no effects on subjects with intermediate or high plasma Hg levels (second and third tertiles, respectively). The C(-1562)T polymorphism had no effects on MMP-9 levels. These findings suggest a significant interaction between the (CA)(n) polymorphism and low levels of Hg exposure, possibly increasing the risk of developing diseases in subjects with H alleles.

Environmental exposure to methylmercury is associated with a decrease in nitric oxide production.

Some studies have recently suggested that mercury (Hg)-exposed populations face increased risks of cardiovascular diseases, and experimental data indicate that such risks might be due to reductions in nitric oxide bioavailability. However, no previous study has examined whether Hg exposure affects plasma nitrite concentrations in humans as an indication of nitric oxide production. Here, we investigated whether there is an association between circulating nitrite and Hg concentrations in whole blood, plasma and hair from an exposed methylmercury (MeHg) population. Hair and blood samples were collected from 238 persons exposed to MeHg from fish consumption. Hg concentrations in plasma (PHg), whole blood (BHg) and hair Hg (HHg) were determined by inductively coupled plasma-mass spectrometry. Mean BHg content was 49.8 +/- 35.2 microg/l, mean PHg was 7.8 +/- 6.9 microg/l and HHg 14.6 +/- 10.6 microg/g. Mean plasma nitrite concentration was 253.2 +/- 105.5 nM. No association was found between plasma nitrite concentration and BHg or HHg concentrations in a univariate model. However, multiple regression models adjusted for gender, age and fish consumption showed a significant association between plasma nitrite and plasma Hg concentration (beta = -0.1, p < 0.001). Our findings constitute preliminary clinical evidence that exposure to MeHg may cause inhibitory effects on the production of endothelial nitric oxide.

Trace element levels in whole blood of riparian villagers of the Brazilian Amazon.

Monitoring the nutritional status of essential elements is of critical importance in human health. However, trace element concentrations in biological fluids are affected by environmental and physiological parameters, and therefore considerable variations can occur between specific population subgroups. Brazil is a large country with much food diversity. Moreover, dietary habits differ from north to south. As an example, the traditional populations of the Brazilian Amazon basin are heavily dependent on fish, fruits, vegetables and manioc for their daily sustenance. However, very few studies have examined to what extent these diets reflect adequate nutritional status for essential elements. Then, in the present study we have evaluated the levels of some trace elements (Cu, Co, Zn Sr, and Rb) in the whole blood of a riparian Brazilian Amazonian population and estimated the influence of age and gender on levels and inter-element interactions in the same population. For this, 253 subjects, aged 15 to 87, from 13 communities situated on the banks of the Tapajós, one of the major tributaries of the Amazon, were randomly selected. The values found for cobalt, copper and strontium in whole blood are in the same range as in other populations. On the other hand, the levels of rubidium and zinc may be considered higher. Moreover, gender was shown to influence Zn and Cu levels while age influenced the concentrations of Sr and Rb in men and Cu in women. Given the scarcity of studies examining nutritional status in traditional communities of the Amazon, our study is the first to provide relevant insight into trace element values in this region and inter-element interactions. This paper is also of particular importance for future studies looking at the possible protective effects of traditional Amazon riparian diets against mercury intake from fish consumption.

Biomarkers of selenium status in the Amazonian context: blood, urine and sequential hair segments.

Selenium (Se) is an essential element and deficit or excess of dietary Se is associated with health disorders. Relatively elevated Se levels have been reported in the Brazilian Amazon, where there are also important annual variations in the availability of different foods. The present study was conducted among six riparian communities of the Tapajós River to evaluate seasonal variations in blood and sequential hair cm Se concentrations, and to examine the relationships between Se in blood and hair, and blood and urine. Two cross-sectional studies were conducted, at the descending water (DWS, n=259) and the rising water (RWS, n=137) seasons, with repeated measures for a subgroup (n=112). Blood Se (B-Se), hair Se (H-Se) and urine Se (U-Se) were determined. Match-paired analyses were used for seasonal comparisons and the method of best fit was used to describe the relationships between biomarkers. B-Se levels presented a very large range (142-2447 microg/l) with no overall seasonal variation (median 284 and 292 microg/l, respectively). Sequential analysis of 13 cm hair strands showed significant variations over time: Se concentrations at the DWS were significantly lower compared with the rising water season (medians: 0.7 and 0.9 microg/g; ranges: 0.2-4.3 microg/g and 0.2-5.4 microg/g, respectively). At both seasons, the relationships between B-Se and H-Se were linear and highly significant (r(2)=67.9 and 63.6, respectively), while the relationship between B-Se and U-Se was best described by a sigmoid curve. Gender, age, education and smoking did not influence Se status or biomarker relationships. Variations in H-Se suggest that there may be seasonal availability of Se sources in local food. For populations presenting a large range and/or elevated Se exposure, sequential analyses of H-Se may provide a good reflection of variations in Se status.

Mercury exposure increases circulating net matrix metalloproteinase (MMP)-2 and MMP-9 activities.

Mercury (Hg) exposure causes health problems that may result from increased oxidative stress and matrix metalloproteinase (MMP) levels. We investigated whether there is an association between the circulating levels of MMP-2, MMP-9, their endogenous inhibitors (the tissue inhibitors of metalloproteinases; TIMPs) and the circulating Hg levels in 159 subjects environmentally exposed to Hg. Blood and plasma Hg were determined by inductively coupled plasma-mass spectrometry (ICP-MS). MMP and TIMP concentrations were measured in plasma samples by gelatin zymography and ELISA respectively. Thiobarbituric acid-reactive species (TBARS) were measured in plasma to assess oxidative stress. Selenium (Se) levels were determined by ICP-MS because it is an antioxidant. The relations between bioindicators of Hg and the metalloproteinases levels were examined using multivariate regression models. While we found no relation between blood or plasma Hg and MMP-9, plasma Hg levels were negatively associated with TIMP-1 and TIMP-2 levels, and thereby with increasing MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios, thus indicating a positive association between plasma Hg and circulating net MMP-9 and MMP-2 activities. These findings provide a new insight into the possible biological mechanisms of Hg toxicity, particularly in cardiovascular diseases.

Human mercury exposure and adverse health effects in the Amazon: a review.

This paper examines issues of human mercury (Hg) exposure and adverse health effects throughout the Amazon region. An extensive review was conducted using bibliographic indexes as well as secondary sources. There are several sources of Hg (mining, deforestation, reservoirs), and exposure takes place through inhalation or from fish consumption. There is a wide range of exposure, with mean hair-Hg levels above 15 microg/g in several Amazonian communities, placing them among the highest reported levels in the world today. Dietary Hg intake has been estimated in the vicinity of 1-2 microg/kg/day, considerably higher than the USEPA RfD of 0.1 microg/kg/day or the World Health Organization recommendation of 0.23 microg/kg/day. Neurobehavioral deficits and, in some cases, clinical signs have been reported both for adults and children in relation to Hg exposure in several Amazonian countries. There is also some evidence of cytogenetic damage, immune alterations, and cardiovascular toxicity. Since fish provide a highly nutritious food source, there is an urgent need to find realistic and feasible solutions that will reduce exposure and toxic risk, while maintaining healthy traditional dietary habits and preserving this unique biodiversity.

Human mercury exposure and adverse health effects in the Amazon: a review / Exposição humana ao mercúrio e efeitos adversos à saúde na Amazônia: uma revisão

This paper examines issues of human mercury (Hg) exposure and adverse health effects throughout the Amazon region. An extensive review was conducted using bibliographic indexes as well as secondary sources. There are several sources of Hg (mining, deforestation, reservoirs), and exposure takes place through inhalation or from fish consumption. There is a wide range of exposure, with mean hair-Hg levels above 15µg/g in several Amazonian communities, placing them among the highest reported levels in the world today. Dietary Hg intake has been estimated in the vicinity of 1-2µg/kg/day, considerably higher than the USEPA RfD of 0.1µg/kg/day or the World Health Organization recommendation of 0.23µg/kg/day. Neurobehavioral deficits and, in some cases, clinical signs have been reported both for adults and children in relation to Hg exposure in several Amazonian countries. There is also some evidence of cytogenetic damage, immune alterations, and cardiovascular toxicity. Since fish provide a highly nutritious food source, there is an urgent need to find realistic and feasible solutions that will reduce exposure and toxic risk, while maintaining healthy traditional dietary habits and preserving this unique biodiversity.

Este artigo examina questões sobre exposição humana ao mercúrio (Hg) e seus efeitos adversos à saúde na Amazônia, com base em extensa revisão da literatura. Diferentes bioindicadores revelam uma ampla faixa de exposição, com teores médios de Hg em cabelo acima de 15µg/g em diversas comunidades amazônicas, situando-as dentre as mais expostas no mundo atualmente. Taxas de ingestão diária de Hg foram estimadas em alguns estudos e situam-se entre 1-2µg/kg/dia, consideravelmente acima das doses de referência estabelecidas pela USEPA (0,1µg/kg/dia) ou pela OMS (0,23µg/kg/dia). Déficits neurocomportamentais e, em alguns casos, sinais clínicos relacionados à exposição mercurial têm sido relatados tanto em adultos quanto em crianças de diversos países amazônicos. Há também evidências de dano citogenético, mudanças imunológicas e toxicidade cardiovascular. Visto que peixe é altamente nutritivo e há diversas fontes de Hg nesta região, existe uma necessidade urgente de encontrar soluções realistas e viáveis capazes de reduzir os níveis de exposição e de risco tóxico, ao mesmo tempo mantendo os hábitos alimentares tradicionais, preservando a biodiversidade píscea e frutífera e melhorando a saúde das populações desfavorecidas e afetadas.