No description available.

The activity of erythrocyte amino levulenic acid dehydratase (ALA-D) and liver and bone lead concentrations were measured in 141 wild rainbow trout from two highway-influenced and two pristine streams. A significant relationship between ALA-D activity and liver lead concentrations among streams (r = 0.157) was observed. However, this relationship was opposite of expected. Trout tissue lead and stream-water lead concentrations were lower than most concentrations observed for control laboratory trout. At these low tissue and water lead concentrations observed in the present study, ALA-D activity cannot be used to document exposure of fish to environmental lead. Other significant correlations with the activity of the enzyme included: trout length (r = -0.411); trout age (r = -0.385); and sediment lead (r = 0.093). Erythrocyte ALA-D activity significantly varied due to sampling period. However, reasons for this deviation cannot be explained from the present study. Multiple regression techniques revealed little concerning trout liver lead concentrations and ALA-D activity relationships. Like ALA-D activity, liver lead concentrations were deemed a poor indicator of organisms' exposure to environmental lead. Bone lead concentrations were the best indicator of environmental contamination. However, the best regression model, which regressed water lead on bone lead, explained only 20.6% of the variation in bone lead burden. In both roadside streams, water lead was positively correlated to turbidity and area precipitation. Water lead concentrations were also positively correlated to discharge in one roadside stream. / M.S.

Lead (Pb²⁺) is an environmental toxin that is known to cause lasting cognitive deficits following early life exposure. Previously, our laboratory demonstrated increased sensitivity to the psychostimulant effects of cocaine in animals with elevated blood Pb²⁺ levels (BLL). This effect was abolished following introduction of dopamine (DA) receptor antagonists, indicating that the dopaminergic (DAergic) system may be a target of Pb²⁺’s toxic effects. However, the biological mechanisms through which Pb²⁺ increased sensitization to cocaine’s psychostimulant effects have not been fully elucidated. There is some disagreement regarding the magnitude and direction of Pb²⁺’s effects on the DAergic system. Furthermore, many studies to date have measured the effects of Pb²⁺ in only one sex (usually male), one exposure, and one or two time-points, making it difficult to determine any potential sex-, age-, and exposure-dependent effects. In the present study, we used a well-validated animal model and Pb²⁺ exposure paradigm that uses chronic dietary exposure to 180ppm and 1500ppm Pb²⁺ acetate (PbAC) in the diet. These levels of Pb²+ in the diet resulted in low and moderate levels of BLLs that on average approximated 4.5 and 22.0µg/dl in young adult rats. These levels of Pb²⁺ exposure are relevant to contemporary levels of BLL in intoxicated children in many cities in the United States and in many parts of the world where Pb²⁺ exposure continues to be a major public health concern. It should be noted that at the low level of Pb²⁺ exposure, the resulting BLL of 4.5µg/dl is just below the current CDC level of action. Using this well-defined rat model of chronic Pb²⁺ exposure, in Aim 1, we measured DA concentration and turnover in the dorsal striatum (STR) of juvenile (PN14), adolescent (PN28), and young adult (PN50) male and female rats. Tyrosine hydroxylase (TH) protein, the rate-limiting step in the synthesis of DA, and phosphorylation of TH at serine 40 (pser40TH) were assessed as an indirect measure of TH activity. Thus, we measured the ratio of pser40TH to total TH protein. We also measured vesicular monoamine transporter-type 2 (VMAT2) levels in the STR, nucleus accumbens (NAC), and olfactory tubercle (OT) since this protein is critical for the sequestration of DA in presynaptic vesicles and has been used as a biomarker for DA terminal integrity. In Aim 2, we examine the effect of chronic Pb²⁺ exposure on D1 and D2 dopamine receptor (D1R and D2R) in the OT, NAC, and STR. Analysis of D1R and D2R is important since the downstream effects of DA are dependent on the DA receptor subtype it activates. In Aim 1, we observed significant increases in DA and its metabolites homovanillic acid (HVA) and 3,4-Dihydroxyphenylacetic acid (DOPAC) in the STR of adolescent and young adult male rats with BLL as low as 4.5µg/dl in the absence of phosphorylation at the serine 40 residue of TH or altered VMAT2 levels. In Aim 2, a significant increase in D2R was detected in the juvenile male rat STR. We also observed increases in D1R expression in adolescent male rats in the NAC, OT, STR, and in the OT of adolescent female rats. Together, these results demonstrate that chronic Pb²⁺ exposure alters DA receptor levels in a manner characteristic of a hyperactive DAergic state. The observations presented in this work suggest that a hyperactive DAergic system underlies the heightened sensitization to cocaine we previously observed in Pb²⁺-exposed animals. This work builds upon the current understanding of how Pb²⁺ modulates the DAergic system and provides some elucidation of the mechanisms underlying increased drug sensitization our laboratory has previously observed in rats exposed to Pb²⁺.

Varios fatores contribuem para o desenvolvimento da anemia, que constitui um dos mais graves problemas de saude publica. A anemia hipocromica microcitica e a forma mais comum em criancas e adolescentes. Dentre as causas desta anemia estao: a) deficiencia de ferro, que resulta de um longo periodo do balanco negativo do micronutriente e causa retardo no crescimento e comprometimento do desempenho cognitivo de criancas; b) contaminacao por chumbo (plumbismo) que tambem afeta o desenvolvimento das criancas, podendo ser agravada nos portadores de polimorfismo da enzima ALAD; c) hemoglobinopatias (hemoglobinas variantes e talassemias), anemias herdadas que afetam 7% da populacao mundial. Devido a alta prevalencia destas patologias, o presente trabalho teve como objetivo estudar um grupo de criancas de escolas publicas, identificando os fatores que contribuem para o desenvolvimento de anemias hipocromicas microciticas e estabelecer relacoes entre as caracteristicas laboratoriais das doencas. Participaram do estudo 427 criancas, com idade entre 6 a 9 anos, sendo 235 do sexo feminino e 192 do sexo masculino, alunos de Escolas Municipais e Estaduais, da zona norte da cidade de Ribeirao Preto-SP. Foram analisados: a) numero global de eritrocitos e leucocitos, concentracao de hemoglobina, hematocrito, indices hematimetricos e distribuicao da amplitude das celulas vermelhas (contador automatico Micros 45 . Horiba ABXR) e calculo do indice matematico RDWI; b) niveis plasmaticos de chumbo (espectrometro de massa com plasma indutivamente acoplado VG Plasmaquad PQIIR) e estudo das delecoes dos polimorfismos da enzima ALAD, por PCR; c) status ferrico pelos niveis de ferritina serica (imunoquimioluminescencia utilizando kit Ferritin Immulite . DPCR e equipamento Immulite 1 - DPCR), receptor de transferrina soluvel (ensaio imunoenzimatico, utilizando o kit Quantikine soluble transferrin receptor da R&D SystemsR e o leitor de microplacas de ELISA READER 210, modelo Microwell System Organon TeknikaR) e calculo do indice sTfR/log ferritina; d) analise das hemoglobinas por eletroforese em acetato de celulose, pH alcalino, por HPLC (sistema automatizado Variant II Bio-RadR e kit gÀ-talassemia Short Program) e PCR para a principal delecao de ¿- talassemias. Com base no criterio recomendado pela OMS para definir anemia (Hb menor que 11,5 g/dL), verificou-se que 75 (17,6%) criancas eram anemicas, sendo 33 (44%) portadoras de algum tipo de hemoglobinopatia, 29 (38,6%) com anemias de causa desconhecida e 13 (17,4%) com anemia por deficiencia de ferro. Das anemias, apenas 14 eram anemias hipocromicas microciticas, sendo que 10 (71,4%) eram algum tipo de hemoglobinopatia, 2 (14,2%) ADF e 2 (14,2%) de causa desconhecida. Na populacao estudada, a prevalencia de hemoglobinopatias foi de 16,6% , a saber: 11,6% com ¿-talassemia; 4% com aumento de Hb F; 3,5% com Hb AS; 2,8% com À-talassemia; 0,96% com ¿/À-talassemia e 0,24% com Hb AC. Os niveis de chumbo plasmatico, em todos os participantes do estudo, estavam dentro do recomendado pelo Center for Disease Control and Prevention (< 10 Êg/dL), nao havendo interferencia do metal na patogenese das anemias. Nao houve associacao entre os polimorfismos da ALAD-1 (ALAD1-1 e ALAD1-2) e os niveis de chumbo plasmatico. Anemia por deficiencia de ferro foi diagnosticada em 3% das criancas e DF em 6,1%, utilizando um cut off de 30 ng/mL para ferritina serica. Houve concordancia na identificacao de hemoglobinopatias utilizando as metodologias eletroforese de hemoglobina em acetato de celulose e HPLC, sendo que estas metodologias nao sao uteis para diagnosticar ¿-talassemia. Para identificar os portadores da delecao de ¿-talassemia (.¿3,7) e necessaria a utilizacao da análise molecular (PCR). A suspeita de Hb S/-talassemia identificada por HPLC deve ser confirmada por análise dos pais e/ou irmãos. A ferritina foi um bom parâmetro para identificar DF precocemente e útil para diferenciar os portadores de hemoglobinopatias dos portadores de DF e ADF. O índice sTfR/log da ferritina foi mais sensível do que o sTfR, na diferenciação de DF e talassemia. No diagnóstico das anemias hipocrômicas microcíticas é necessário analisar um conjunto de determinações, incluindo exame hematológico, status férrico, perfil eletroforético, em alguns casos incluindo avaliação dos familiares, e análise molecular das hemoglobinopatias. / Several factors contribute to the development of anemia, which constitutes one of the most serious problems in public health. The hypochromic microcytic anemia is the most common type in children and adolescents. Among the causes for this type of anemia are: a) iron deficiency, which results from a long period of negative balance of the micronutrient, causing delay in growth and compromising the cognitive performance of the children; b) contamination by lead (lead poisoning), which also affects the development of children, and may be aggravated in carriers of polymorphism of the enzyme ALAD; c) hemoglobinopathies (variants hemoglobin and thalassemia), inherited anemia that affects 7% of the world population. Due to the high prevalence of these pathologies, the present study aimed at studying a group of children from public schools, identifying the factors that contribute to the development of hypochromic microcytic anemia and establishing relations between the laboratorial characteristics of the diseases. The study had the participation of 427 children, aged between 6 and 9 years old, being 235 female and 192 male students from Municipal and State Schools in the north area of Ribeirao Preto-SP. It analyzed: a) number of erythrocytes and leucocytes, hemoglobin concentration, hematocrit, red cell indices and red cell distribution width (automatic counter Micros 45 . Horiba ABXR) and calculation of the mathematical index RDWI; b) plasma lead levels (inductively coupled plasma mass spectrometer VG PlasmaQuad PQIIR) and study of the deletions of the polymorphisms of the enzyme ALAD, by PCR; c) iron status by serum ferritin levels (immunochemiluminescence using the kit Ferritin Immulite . DPCR and the equipment Immulite 1 - DPCR), soluble transferrin receptor (enzyme immune assay, using the kit Quantikine soluble transferrin receptor of R&D SystemsR and the microplate reader ELISA READER 210, model Microwell System Organon TeknikaR) and calculation of the sTfR/log ferritin index; d) hemoglobin analysis by electrophoresis on cellulose acetate at alkaline pH, HPLC (automated system Variant II Bio-RadR and the kit gÀ-thalassemia Short Program) and PCR for the main deletion of ¿-thalassemias. Based on the WHO criteria by to define anemia (Hb under 11.5 g/dL), it was verified that 75 (17.6%) children were anemic, being 33 (44%) with hemoglobinopathy, 29 (38.6%) with anemia of unknown causes and 13 (17.4%) with iron deficiency anemia. Among the anemias, only 14 were hypochromic microcytic, 10 (71.4%) being some sort of hemoglobinopathy, 2 (14.2%) due to iron deficiency and 2 (14.2%) due to unknown causes. In the studied population, the prevalence of hemoglobinopathies was 16.6%, namely: 11.6% with ¿-thalassemia; 4% with Hb F elevated; 3.5% with Hb AS; 2.8% with À- thalassemia; 0.96% with ¿/À-thalassemia and 0.24% with Hb AC. The plasma lead levels, in all participants of the study, were within the levels recommended by the Center for Disease Control and Prevention (< 10 Êg/dL), without the interference of the metal in the pathogenesis of the anemias. There was no significant association between the polymorphisms of the ALAD-1 (ALAD1-1 and ALAD1-2) and the plasma lead levels. Iron deficiency anemia was diagnosed in 3% of the children and ID in 6.1%, using a cutoff of 30 ng/mL for serum ferritin. There was agreement in the identification of hemoglobinopathies using the methodologies electrophoresis of hemoglobin in cellulose acetate and the HPLC, as these methodologies are not useful to diagnose ¿-thalassemia. In order to identify the carriers of ¿-thalassemia gene deletion (.¿3,7) it is necessary to use the molecular analysis (PCR). The suspicion of Hb S/À-thalassemia identified by HPLC must be confirmed through the analysis iv of the parents and/or siblings. The ferritin was a good parameter to identify ID early and useful to differ the carriers of hemoglobinopathies of the carriers of ID and IDA. The sTfR/log ferritin level was more sensitive than the sTfR, in the differentiation of ID and thalassemia. In the diagnosis of the hypochromic microcytic anemias, it is necessary to analyze a set of determinations, including hematological exam, iron status, electrophoretic profile, in some cases including relatives, and molecular analysis of the hemoglobinopathies.

A exposição ambiental ao chumbo é uma das questões mais sérias de contaminação de populações do ponto de vista de saúde pública. Mesmo em pequenas quantidades, o chumbo causa mudanças bioquímicas e neurológicas, convulsões e hiperatividade. No Brasil, não existe programa nacional para detecção de crianças contaminadas por este metal, as quais são mais sensíveis aos efeitos deletérios resultantes da exposição crônica a baixas concentrações de chumbo. A maioria dos trabalhos que comprovaram a associação entre exposição ambiental a chumbo no passado e problemas no desenvolvimento neurológico utilizou dentina de dentes decíduos como tecido marcador de exposição. Trabalhos do nosso grupo indicam que o esmalte superficial de dentes decíduos seria um bom marcador cumulativo da exposição passada ao chumbo, sendo que esse tecido apresenta consideráveis vantagens do ponto de vista de acesso e desenvolvimento de testes para monitoramento ambiental. Uma questão importante é verificar se as concentrações de chumbo encontradas no esmalte superficial decíduo variam ao longo do tempo em crianças de baixa exposição. Outra questão importante é verificar se há correlações entre as concentrações de chumbo no esmalte superficial e aquelas dos principais fluidos corporais a partir dos quais o chumbo seria acumulado no esmalte, que são sangue total, plasma e saliva. Assim, o objetivo deste trabalho foi verificar in vivo, por meio de testes em esmalte em dentes decíduos, se o chumbo acumulado nos primeiros micrometros do esmalte aumenta ao longo de três anos e se as concentrações de chumbo encontradas no esmalte apresentam correlação com aquelas encontradas no sangue total, plasma e saliva. A amostra inicial foi constituída por 50 crianças com idade de 2 a 3 anos procedentes de Ribeirão Preto que estavam recebendo atendimento odontológico na Clínica Infantil da Faculdade de Odontologia de Ribeirão Preto USP e alunos da Creche Carochinha (USPRibeirão Preto). Obtiveram-se as seguintes amostras: primeira etapa (2009): 01 amostra de sangue total e 01 amostra de esmalte de um incisivo central superior; segunda etapa (2010): 01 amostra de sangue total, 01 amostra de plasma sanguíneo, 01 amostra de saliva e 01 amostra de esmalte do dente contralateral. terceira etapa (2011): 01 amostra de sangue total, 01 amostra de plasma sanguíneo, 01 amostra de saliva e 02 amostras de amostra de esmalte dos incisivos laterais. O fósforo foi determinado colorimetricamente, para calcular a profundidade dos testes de esmalte. As concentrações de chumbo no plasma, saliva e esmalte dental foram determinadas por espectrometria de massas com plasma indutivamente acoplado (ICPMS) e no sangue total, por espectrometria de absorção atômica com forno de grafite. Muitas crianças ou seus responsáveis não permitiram a coleta de sangue em algum dos períodos, e assim ao longo dos 3 anos tivemos participação efetiva de 20 crianças. Em 2009, a concentração de chumbo no sangue total variou de 0,2 &mu;g/dL a 7,48 &mu;g/dL e teve como a mediana 0,26 &mu;g/dL. Apenas uma criança apresentou nível de chumbo no sangue 5 &mu;g/dL. Em 2010, a concentração de chumbo no sangue total variou de 0.2 &mu;g/dL a 3,8 &mu;g/dL e teve como a mediana 0,32 &mu;g/dL. Em 2011, a concentração de chumbo no sangue variou de 1,15 &mu;g/dL a 3,55 &mu;g/dL e teve como mediana 0,95 &mu;g/dL. Os dados de chumbo no sangue não apresentam diferenças estatisticamente significantes entre os grupos ao longo dos anos (p>0.05). Em 2010, valores de chumbo no plasma variaram de 0,29 3,20 &mu;g/L e a mediana foi 0,49. Em 2011, variaram de 0,38 1,60 &mu;g/L com mediana 0,52 &mu;g/L. A concentração de chumbo na saliva em 2010 variou de 0,02 3,00 &mu;g/L, com mediana de 0,34 &mu;g/L. Em 2011, esses valores variaram de 0,02 4,27 &mu;g/L e a mediana foi de 0,19 &mu;g/L. Para as concentrações de chumbo no plasma e na saliva, não houve diferenças estatisticamente significantes entre os grupos (Saliva 2010 x Saliva 2011; Plasma 2010 x Plasma 2011) (teste de Mann Whitney; p>0.05). No caso dos dados obtidos no esmalte dentário, os valores de chumbo foram recalculados para uma mesma profundidade, que foi de 3,4 &mu;m. Nenhum dos grupos (Esmalte 2009, Esmalte 2010 e Esmalte 2011) teve distribuição normal, e não houve diferença entre nas concentrações de chumbo encontradas ao longo dos anos, com medianas de 36, 35 e 38 &mu;g/g em 2009, 2010 e 2011, respectivamente (p=0,71, teste de Kruskal-Wallis). A análise de correlação foi feita após a transformação logarítmica (log10) de todos os valores. Mesmo após esta transformação, dois grupos ainda não apresentaram distribuição normal, o grupo Plasma 2011 e Esmalte 2010. As associações que envolviam estes grupos foram testadas utilizando-se a correlação de Spearman, enquanto todas as demais associações foram testadas utilizando-se o teste de correlação de Pearson. As correlações significativas positivas encontradas foram: entre Sangue Total 2009 e Sangue Total 2010 (rP = 0,64; p = 0,002) ; Sangue Total 2010 e Sangue Total 2011 (rP = 0,66; p = 0,002); Esmalte 2011 e Sangue Total 2009 (rP= 0,44; p=0,05) e entre Esmalte 2009 e Esmalte 2010 (rS = 0,45 e p=0,03). Houve uma associação inversa entre a Saliva 2010 e Esmalte 2011 (rP = - 0,55; p=0,013). Conclusão: Os valores de chumbo obtidos em todas as amostras ao longo de 3 anos caracterizam baixa exposição a chumbo no grupo estudado. As concentrações de chumbo no sangue, saliva, plasma e esmalte não variaram ao longo do tempo. Das 28 associações testadas, foram estatisticamente significantes e positivas aquelas entre o Sangue Total 2009 e o Esmalte 2011 e entre o Esmalte 2009 e Esmalte 2010. A associação entre Saliva 2010 e Esmalte 2011 foi inversa. Os resultados sugerem que o esmalte tenha associação com a exposição de chumbo passada, neste estudo caracterizado pelos valores de chumbo no sangue total. Os resultados sugerem que o esmalte possa ser um biomarcador fidedigno para avaliar o grau de exposição a chumbo em populações com baixa exposição a este metal, uma vez que o esmalte superficial de dentes decíduos não incorporou chumbo em quantidades significativas entre 2 e 5 anos de idade em crianças com baixa exposição e baixa atividade de cárie. / Environmental exposure to lead is one of the most serious contamination problems that affect public health. Even in small amounts, lead can cause neurological and biochemical changes, such as mental problems and hyperactivity. In Brazil, there is no program for the detection of children contaminated by this metal. Children are more sensitive to the deleterious effects of chronic lead exposure. Studies that proved association between environmental exposure to lead and neurological developmental problems used dentine of primary teeth as a marker of lead exposure. Studies by our group suggest that superficial enamel of deciduous teeth would be a good cumulative marker of past exposure to lead, and this tissue has considerable advantages regarding access and the perspective of development of tests for environmental monitoring of children. An important question is whether the concentrations of lead found in deciduous enamel surface vary over time in children with low exposure and if there are correlations between the concentrations of lead in the enamel surface and those of the main body fluids from which the lead was accumulated in the enamel, which are whole blood, plasma and saliva. The aims of this study was to investigate in vivo, by testing lead concentration in deciduous enamel of primary teeth, if the lead accumulated in the first micrometers of enamel increases along three years and if the concentrations of lead found in enamel surface were correlated with those found in whole blood, plasma and saliva. The initial sample consisted of 50 children aged 2 to 3 years from Ribeirão Preto, who were receiving dental care at Children\'s Clinic of the Faculty of Dentistry of Ribeirão Preto - USP and students of Nursery Carochinha (USP-Ribeirão Preto). The following samples were obtained: first stage (2009): 01 sample of whole blood and 01 sample of enamel of a central upper incisor, second stage (2010): 01 sample of whole blood, 01 sample of blood plasma, 01 sample of saliva and 01 sample of enamel from the contralateral tooth; third stage (2011): 01 sample of whole blood, 01 sample of blood plasma, 01 sample of saliva and 02 enamel samples of lateral upper incisors. Phosphorus was determined by a colorimetric method, in order to calculate the depth of enamel tests. Lead concentrations in plasma, saliva and enamel were determined by inductively coupled plasma mass spectrometry (ICPMS) and whole blood by atomic absorption spectrometer with graphite furnace. Many children or their guardians did not allow the collection of blood in any of the periods, and thus, over the three years, we had the enrollment of only 20 children. In 2009, the concentration of lead in whole blood varied from 0.2 &mu;g / dL to 7.48 &mu;g /dL and the median was 0.26 &mu;g/dL. Only one child had a blood lead level 5 &mu;g/ dL. In 2010, the concentration of lead in whole blood ranged from 0.2 &mu;g/dL to 3.8 &mu;g/dL and the median was 0.32 &mu;g/dL. In 2011, the concentration of lead in blood ranged from 1.15 &mu;g/dL to 3.55 &mu;g/dL and the median was 0.95 &mu;g/dL. The blood lead data do not show statistically significant differences over the years (p> 0.05). In 2010, values of lead in plasma ranged from 0.29 to 3.20 &mu;g/L and the median was 0.49 &mu;g/L. In 2011, lead levels in plasma ranged from 0.38 to 1.60 &mu;g/L with median 0.52 &mu;g/L. The lead concentration in Saliva 2010 ranged from 0.02 to 3.00&mu; g/L, median 0.34 &mu;g/L. In 2011, these values ranged from 0.02 to 4.27 &mu;g/L and the median was 0.19 &mu;g/L. For lead concentrations in plasma and saliva, there were no statistically significant differences between groups (Saliva 2010 x Saliva 2011; Plasma 2010 x Plasma 2011)(Mann-Whitney test, p> 0.05). To analyze enamel samples, the values of lead were recalculated so they would reflect the lead found in one same depth, which was 3.4 micrometers. None of the groups (enamel from 2009, enamel from 2010 and enamel from 2011) presented normal distribution. There was no statistically significant difference between these three groups (p=0.71, Kruskal-Wallis). A correlation analysis was performed after logarithmic transformation (log10) of all values. Even after this transformation, two groups still did not exhibit normal distribution, which were Plasma 2011 & Enamel 2010. The associations that involved these two groups were tested using the Spearman correlation test, while all other associations were tested using the Pearson correlation test. The significant positive correlations found were: Whole Blood 2009 and Whole Blood 2010 (rP = 0,64; p = 0,002) ; Whole Blood 2010 and Whole Blood 2011 (rP = 0,66; p = 0,002); between Enamel 2011 and Whole Blood 2009 (rP= 0.44, p = 0.05) and between Enamel 2009 and Enamel 2010 (rS= 0.45, p= 0.03). There was an inverse association between Saliva 2010 and Enamel 2011 (rP= - 0,55; p = 0,013). Conclusion: The lead values obtained in all samples over three years characterized low exposure to lead by the group studied. Lead concentrations in blood, saliva, plasma and enamel did not vary over time. Of the 28 associations tested, the ones between Whole Blood 2009 and 2011 and between Enamel 2009 and 2010 were positive and significant. The association between Saliva 2010 and Enamel 2011 was negative and significant. The results suggest that the lead found in the enamel is correlated with past exposure to lead characterized in this study by the yearly whole blood lead data. The results further suggest that the dental enamel can be a reliable marker to assess the degree of exposure to lead of populations, since the primary teeth´s enamel surface did not incorporate lead in substantial quantities between 2 and 5 years in children with low exposure to this metal and low caries activity.

Includes bibliographies. / xiv, 233, [102] leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / This thesis examines the relationship between environmental lead exposure and later emotional and behavioural problems experienced by 11-13 year old children enrolled in the Port Pirie Cohort Study (PPCS). The PPCS is the first study to monitor prospectively the association between lifetime blood lead exposure and children's behaviour. Prenatal and postnatal measures of lead exposure are collected from birth along with a large number of biomedical, socio-environmental and familial factors that might confound the relationship between lead exposure and children's behaviour. / Thesis (Ph.D.)--University of Adelaide, Dept. of Psychiatry, 1997

A exposição ambiental ao chumbo é uma das questões mais sérias de contaminação de populações do ponto de vista de saúde pública. Mesmo em pequenas quantidades, o chumbo causa mudanças bioquímicas e neurológicas, convulsões e hiperatividade. No Brasil, não existe programa nacional para detecção de crianças contaminadas por este metal, as quais são mais sensíveis aos efeitos deletérios resultantes da exposição crônica a baixas concentrações de chumbo. A maioria dos trabalhos que comprovaram a associação entre exposição ambiental a chumbo no passado e problemas no desenvolvimento neurológico utilizou dentina de dentes decíduos como tecido marcador de exposição. Trabalhos do nosso grupo indicam que o esmalte superficial de dentes decíduos seria um bom marcador cumulativo da exposição passada ao chumbo, sendo que esse tecido apresenta consideráveis vantagens do ponto de vista de acesso e desenvolvimento de testes para monitoramento ambiental. Uma questão importante é verificar se as concentrações de chumbo encontradas no esmalte superficial decíduo variam ao longo do tempo em crianças de baixa exposição. Outra questão importante é verificar se há correlações entre as concentrações de chumbo no esmalte superficial e aquelas dos principais fluidos corporais a partir dos quais o chumbo seria acumulado no esmalte, que são sangue total, plasma e saliva. Assim, o objetivo deste trabalho foi verificar in vivo, por meio de testes em esmalte em dentes decíduos, se o chumbo acumulado nos primeiros micrometros do esmalte aumenta ao longo de três anos e se as concentrações de chumbo encontradas no esmalte apresentam correlação com aquelas encontradas no sangue total, plasma e saliva. A amostra inicial foi constituída por 50 crianças com idade de 2 a 3 anos procedentes de Ribeirão Preto que estavam recebendo atendimento odontológico na Clínica Infantil da Faculdade de Odontologia de Ribeirão Preto USP e alunos da Creche Carochinha (USPRibeirão Preto). Obtiveram-se as seguintes amostras: primeira etapa (2009): 01 amostra de sangue total e 01 amostra de esmalte de um incisivo central superior; segunda etapa (2010): 01 amostra de sangue total, 01 amostra de plasma sanguíneo, 01 amostra de saliva e 01 amostra de esmalte do dente contralateral. terceira etapa (2011): 01 amostra de sangue total, 01 amostra de plasma sanguíneo, 01 amostra de saliva e 02 amostras de amostra de esmalte dos incisivos laterais. O fósforo foi determinado colorimetricamente, para calcular a profundidade dos testes de esmalte. As concentrações de chumbo no plasma, saliva e esmalte dental foram determinadas por espectrometria de massas com plasma indutivamente acoplado (ICPMS) e no sangue total, por espectrometria de absorção atômica com forno de grafite. Muitas crianças ou seus responsáveis não permitiram a coleta de sangue em algum dos períodos, e assim ao longo dos 3 anos tivemos participação efetiva de 20 crianças. Em 2009, a concentração de chumbo no sangue total variou de 0,2 &mu;g/dL a 7,48 &mu;g/dL e teve como a mediana 0,26 &mu;g/dL. Apenas uma criança apresentou nível de chumbo no sangue 5 &mu;g/dL. Em 2010, a concentração de chumbo no sangue total variou de 0.2 &mu;g/dL a 3,8 &mu;g/dL e teve como a mediana 0,32 &mu;g/dL. Em 2011, a concentração de chumbo no sangue variou de 1,15 &mu;g/dL a 3,55 &mu;g/dL e teve como mediana 0,95 &mu;g/dL. Os dados de chumbo no sangue não apresentam diferenças estatisticamente significantes entre os grupos ao longo dos anos (p>0.05). Em 2010, valores de chumbo no plasma variaram de 0,29 3,20 &mu;g/L e a mediana foi 0,49. Em 2011, variaram de 0,38 1,60 &mu;g/L com mediana 0,52 &mu;g/L. A concentração de chumbo na saliva em 2010 variou de 0,02 3,00 &mu;g/L, com mediana de 0,34 &mu;g/L. Em 2011, esses valores variaram de 0,02 4,27 &mu;g/L e a mediana foi de 0,19 &mu;g/L. Para as concentrações de chumbo no plasma e na saliva, não houve diferenças estatisticamente significantes entre os grupos (Saliva 2010 x Saliva 2011; Plasma 2010 x Plasma 2011) (teste de Mann Whitney; p>0.05). No caso dos dados obtidos no esmalte dentário, os valores de chumbo foram recalculados para uma mesma profundidade, que foi de 3,4 &mu;m. Nenhum dos grupos (Esmalte 2009, Esmalte 2010 e Esmalte 2011) teve distribuição normal, e não houve diferença entre nas concentrações de chumbo encontradas ao longo dos anos, com medianas de 36, 35 e 38 &mu;g/g em 2009, 2010 e 2011, respectivamente (p=0,71, teste de Kruskal-Wallis). A análise de correlação foi feita após a transformação logarítmica (log10) de todos os valores. Mesmo após esta transformação, dois grupos ainda não apresentaram distribuição normal, o grupo Plasma 2011 e Esmalte 2010. As associações que envolviam estes grupos foram testadas utilizando-se a correlação de Spearman, enquanto todas as demais associações foram testadas utilizando-se o teste de correlação de Pearson. As correlações significativas positivas encontradas foram: entre Sangue Total 2009 e Sangue Total 2010 (rP = 0,64; p = 0,002) ; Sangue Total 2010 e Sangue Total 2011 (rP = 0,66; p = 0,002); Esmalte 2011 e Sangue Total 2009 (rP= 0,44; p=0,05) e entre Esmalte 2009 e Esmalte 2010 (rS = 0,45 e p=0,03). Houve uma associação inversa entre a Saliva 2010 e Esmalte 2011 (rP = - 0,55; p=0,013). Conclusão: Os valores de chumbo obtidos em todas as amostras ao longo de 3 anos caracterizam baixa exposição a chumbo no grupo estudado. As concentrações de chumbo no sangue, saliva, plasma e esmalte não variaram ao longo do tempo. Das 28 associações testadas, foram estatisticamente significantes e positivas aquelas entre o Sangue Total 2009 e o Esmalte 2011 e entre o Esmalte 2009 e Esmalte 2010. A associação entre Saliva 2010 e Esmalte 2011 foi inversa. Os resultados sugerem que o esmalte tenha associação com a exposição de chumbo passada, neste estudo caracterizado pelos valores de chumbo no sangue total. Os resultados sugerem que o esmalte possa ser um biomarcador fidedigno para avaliar o grau de exposição a chumbo em populações com baixa exposição a este metal, uma vez que o esmalte superficial de dentes decíduos não incorporou chumbo em quantidades significativas entre 2 e 5 anos de idade em crianças com baixa exposição e baixa atividade de cárie. / Environmental exposure to lead is one of the most serious contamination problems that affect public health. Even in small amounts, lead can cause neurological and biochemical changes, such as mental problems and hyperactivity. In Brazil, there is no program for the detection of children contaminated by this metal. Children are more sensitive to the deleterious effects of chronic lead exposure. Studies that proved association between environmental exposure to lead and neurological developmental problems used dentine of primary teeth as a marker of lead exposure. Studies by our group suggest that superficial enamel of deciduous teeth would be a good cumulative marker of past exposure to lead, and this tissue has considerable advantages regarding access and the perspective of development of tests for environmental monitoring of children. An important question is whether the concentrations of lead found in deciduous enamel surface vary over time in children with low exposure and if there are correlations between the concentrations of lead in the enamel surface and those of the main body fluids from which the lead was accumulated in the enamel, which are whole blood, plasma and saliva. The aims of this study was to investigate in vivo, by testing lead concentration in deciduous enamel of primary teeth, if the lead accumulated in the first micrometers of enamel increases along three years and if the concentrations of lead found in enamel surface were correlated with those found in whole blood, plasma and saliva. The initial sample consisted of 50 children aged 2 to 3 years from Ribeirão Preto, who were receiving dental care at Children\'s Clinic of the Faculty of Dentistry of Ribeirão Preto - USP and students of Nursery Carochinha (USP-Ribeirão Preto). The following samples were obtained: first stage (2009): 01 sample of whole blood and 01 sample of enamel of a central upper incisor, second stage (2010): 01 sample of whole blood, 01 sample of blood plasma, 01 sample of saliva and 01 sample of enamel from the contralateral tooth; third stage (2011): 01 sample of whole blood, 01 sample of blood plasma, 01 sample of saliva and 02 enamel samples of lateral upper incisors. Phosphorus was determined by a colorimetric method, in order to calculate the depth of enamel tests. Lead concentrations in plasma, saliva and enamel were determined by inductively coupled plasma mass spectrometry (ICPMS) and whole blood by atomic absorption spectrometer with graphite furnace. Many children or their guardians did not allow the collection of blood in any of the periods, and thus, over the three years, we had the enrollment of only 20 children. In 2009, the concentration of lead in whole blood varied from 0.2 &mu;g / dL to 7.48 &mu;g /dL and the median was 0.26 &mu;g/dL. Only one child had a blood lead level 5 &mu;g/ dL. In 2010, the concentration of lead in whole blood ranged from 0.2 &mu;g/dL to 3.8 &mu;g/dL and the median was 0.32 &mu;g/dL. In 2011, the concentration of lead in blood ranged from 1.15 &mu;g/dL to 3.55 &mu;g/dL and the median was 0.95 &mu;g/dL. The blood lead data do not show statistically significant differences over the years (p> 0.05). In 2010, values of lead in plasma ranged from 0.29 to 3.20 &mu;g/L and the median was 0.49 &mu;g/L. In 2011, lead levels in plasma ranged from 0.38 to 1.60 &mu;g/L with median 0.52 &mu;g/L. The lead concentration in Saliva 2010 ranged from 0.02 to 3.00&mu; g/L, median 0.34 &mu;g/L. In 2011, these values ranged from 0.02 to 4.27 &mu;g/L and the median was 0.19 &mu;g/L. For lead concentrations in plasma and saliva, there were no statistically significant differences between groups (Saliva 2010 x Saliva 2011; Plasma 2010 x Plasma 2011)(Mann-Whitney test, p> 0.05). To analyze enamel samples, the values of lead were recalculated so they would reflect the lead found in one same depth, which was 3.4 micrometers. None of the groups (enamel from 2009, enamel from 2010 and enamel from 2011) presented normal distribution. There was no statistically significant difference between these three groups (p=0.71, Kruskal-Wallis). A correlation analysis was performed after logarithmic transformation (log10) of all values. Even after this transformation, two groups still did not exhibit normal distribution, which were Plasma 2011 & Enamel 2010. The associations that involved these two groups were tested using the Spearman correlation test, while all other associations were tested using the Pearson correlation test. The significant positive correlations found were: Whole Blood 2009 and Whole Blood 2010 (rP = 0,64; p = 0,002) ; Whole Blood 2010 and Whole Blood 2011 (rP = 0,66; p = 0,002); between Enamel 2011 and Whole Blood 2009 (rP= 0.44, p = 0.05) and between Enamel 2009 and Enamel 2010 (rS= 0.45, p= 0.03). There was an inverse association between Saliva 2010 and Enamel 2011 (rP= - 0,55; p = 0,013). Conclusion: The lead values obtained in all samples over three years characterized low exposure to lead by the group studied. Lead concentrations in blood, saliva, plasma and enamel did not vary over time. Of the 28 associations tested, the ones between Whole Blood 2009 and 2011 and between Enamel 2009 and 2010 were positive and significant. The association between Saliva 2010 and Enamel 2011 was negative and significant. The results suggest that the lead found in the enamel is correlated with past exposure to lead characterized in this study by the yearly whole blood lead data. The results further suggest that the dental enamel can be a reliable marker to assess the degree of exposure to lead of populations, since the primary teeth´s enamel surface did not incorporate lead in substantial quantities between 2 and 5 years in children with low exposure to this metal and low caries activity.

Varios fatores contribuem para o desenvolvimento da anemia, que constitui um dos mais graves problemas de saude publica. A anemia hipocromica microcitica e a forma mais comum em criancas e adolescentes. Dentre as causas desta anemia estao: a) deficiencia de ferro, que resulta de um longo periodo do balanco negativo do micronutriente e causa retardo no crescimento e comprometimento do desempenho cognitivo de criancas; b) contaminacao por chumbo (plumbismo) que tambem afeta o desenvolvimento das criancas, podendo ser agravada nos portadores de polimorfismo da enzima ALAD; c) hemoglobinopatias (hemoglobinas variantes e talassemias), anemias herdadas que afetam 7% da populacao mundial. Devido a alta prevalencia destas patologias, o presente trabalho teve como objetivo estudar um grupo de criancas de escolas publicas, identificando os fatores que contribuem para o desenvolvimento de anemias hipocromicas microciticas e estabelecer relacoes entre as caracteristicas laboratoriais das doencas. Participaram do estudo 427 criancas, com idade entre 6 a 9 anos, sendo 235 do sexo feminino e 192 do sexo masculino, alunos de Escolas Municipais e Estaduais, da zona norte da cidade de Ribeirao Preto-SP. Foram analisados: a) numero global de eritrocitos e leucocitos, concentracao de hemoglobina, hematocrito, indices hematimetricos e distribuicao da amplitude das celulas vermelhas (contador automatico Micros 45 . Horiba ABXR) e calculo do indice matematico RDWI; b) niveis plasmaticos de chumbo (espectrometro de massa com plasma indutivamente acoplado VG Plasmaquad PQIIR) e estudo das delecoes dos polimorfismos da enzima ALAD, por PCR; c) status ferrico pelos niveis de ferritina serica (imunoquimioluminescencia utilizando kit Ferritin Immulite . DPCR e equipamento Immulite 1 - DPCR), receptor de transferrina soluvel (ensaio imunoenzimatico, utilizando o kit Quantikine soluble transferrin receptor da R&D SystemsR e o leitor de microplacas de ELISA READER 210, modelo Microwell System Organon TeknikaR) e calculo do indice sTfR/log ferritina; d) analise das hemoglobinas por eletroforese em acetato de celulose, pH alcalino, por HPLC (sistema automatizado Variant II Bio-RadR e kit gÀ-talassemia Short Program) e PCR para a principal delecao de ¿- talassemias. Com base no criterio recomendado pela OMS para definir anemia (Hb menor que 11,5 g/dL), verificou-se que 75 (17,6%) criancas eram anemicas, sendo 33 (44%) portadoras de algum tipo de hemoglobinopatia, 29 (38,6%) com anemias de causa desconhecida e 13 (17,4%) com anemia por deficiencia de ferro. Das anemias, apenas 14 eram anemias hipocromicas microciticas, sendo que 10 (71,4%) eram algum tipo de hemoglobinopatia, 2 (14,2%) ADF e 2 (14,2%) de causa desconhecida. Na populacao estudada, a prevalencia de hemoglobinopatias foi de 16,6% , a saber: 11,6% com ¿-talassemia; 4% com aumento de Hb F; 3,5% com Hb AS; 2,8% com À-talassemia; 0,96% com ¿/À-talassemia e 0,24% com Hb AC. Os niveis de chumbo plasmatico, em todos os participantes do estudo, estavam dentro do recomendado pelo Center for Disease Control and Prevention (< 10 Êg/dL), nao havendo interferencia do metal na patogenese das anemias. Nao houve associacao entre os polimorfismos da ALAD-1 (ALAD1-1 e ALAD1-2) e os niveis de chumbo plasmatico. Anemia por deficiencia de ferro foi diagnosticada em 3% das criancas e DF em 6,1%, utilizando um cut off de 30 ng/mL para ferritina serica. Houve concordancia na identificacao de hemoglobinopatias utilizando as metodologias eletroforese de hemoglobina em acetato de celulose e HPLC, sendo que estas metodologias nao sao uteis para diagnosticar ¿-talassemia. Para identificar os portadores da delecao de ¿-talassemia (.¿3,7) e necessaria a utilizacao da análise molecular (PCR). A suspeita de Hb S/-talassemia identificada por HPLC deve ser confirmada por análise dos pais e/ou irmãos. A ferritina foi um bom parâmetro para identificar DF precocemente e útil para diferenciar os portadores de hemoglobinopatias dos portadores de DF e ADF. O índice sTfR/log da ferritina foi mais sensível do que o sTfR, na diferenciação de DF e talassemia. No diagnóstico das anemias hipocrômicas microcíticas é necessário analisar um conjunto de determinações, incluindo exame hematológico, status férrico, perfil eletroforético, em alguns casos incluindo avaliação dos familiares, e análise molecular das hemoglobinopatias. / Several factors contribute to the development of anemia, which constitutes one of the most serious problems in public health. The hypochromic microcytic anemia is the most common type in children and adolescents. Among the causes for this type of anemia are: a) iron deficiency, which results from a long period of negative balance of the micronutrient, causing delay in growth and compromising the cognitive performance of the children; b) contamination by lead (lead poisoning), which also affects the development of children, and may be aggravated in carriers of polymorphism of the enzyme ALAD; c) hemoglobinopathies (variants hemoglobin and thalassemia), inherited anemia that affects 7% of the world population. Due to the high prevalence of these pathologies, the present study aimed at studying a group of children from public schools, identifying the factors that contribute to the development of hypochromic microcytic anemia and establishing relations between the laboratorial characteristics of the diseases. The study had the participation of 427 children, aged between 6 and 9 years old, being 235 female and 192 male students from Municipal and State Schools in the north area of Ribeirao Preto-SP. It analyzed: a) number of erythrocytes and leucocytes, hemoglobin concentration, hematocrit, red cell indices and red cell distribution width (automatic counter Micros 45 . Horiba ABXR) and calculation of the mathematical index RDWI; b) plasma lead levels (inductively coupled plasma mass spectrometer VG PlasmaQuad PQIIR) and study of the deletions of the polymorphisms of the enzyme ALAD, by PCR; c) iron status by serum ferritin levels (immunochemiluminescence using the kit Ferritin Immulite . DPCR and the equipment Immulite 1 - DPCR), soluble transferrin receptor (enzyme immune assay, using the kit Quantikine soluble transferrin receptor of R&D SystemsR and the microplate reader ELISA READER 210, model Microwell System Organon TeknikaR) and calculation of the sTfR/log ferritin index; d) hemoglobin analysis by electrophoresis on cellulose acetate at alkaline pH, HPLC (automated system Variant II Bio-RadR and the kit gÀ-thalassemia Short Program) and PCR for the main deletion of ¿-thalassemias. Based on the WHO criteria by to define anemia (Hb under 11.5 g/dL), it was verified that 75 (17.6%) children were anemic, being 33 (44%) with hemoglobinopathy, 29 (38.6%) with anemia of unknown causes and 13 (17.4%) with iron deficiency anemia. Among the anemias, only 14 were hypochromic microcytic, 10 (71.4%) being some sort of hemoglobinopathy, 2 (14.2%) due to iron deficiency and 2 (14.2%) due to unknown causes. In the studied population, the prevalence of hemoglobinopathies was 16.6%, namely: 11.6% with ¿-thalassemia; 4% with Hb F elevated; 3.5% with Hb AS; 2.8% with À- thalassemia; 0.96% with ¿/À-thalassemia and 0.24% with Hb AC. The plasma lead levels, in all participants of the study, were within the levels recommended by the Center for Disease Control and Prevention (< 10 Êg/dL), without the interference of the metal in the pathogenesis of the anemias. There was no significant association between the polymorphisms of the ALAD-1 (ALAD1-1 and ALAD1-2) and the plasma lead levels. Iron deficiency anemia was diagnosed in 3% of the children and ID in 6.1%, using a cutoff of 30 ng/mL for serum ferritin. There was agreement in the identification of hemoglobinopathies using the methodologies electrophoresis of hemoglobin in cellulose acetate and the HPLC, as these methodologies are not useful to diagnose ¿-thalassemia. In order to identify the carriers of ¿-thalassemia gene deletion (.¿3,7) it is necessary to use the molecular analysis (PCR). The suspicion of Hb S/À-thalassemia identified by HPLC must be confirmed through the analysis iv of the parents and/or siblings. The ferritin was a good parameter to identify ID early and useful to differ the carriers of hemoglobinopathies of the carriers of ID and IDA. The sTfR/log ferritin level was more sensitive than the sTfR, in the differentiation of ID and thalassemia. In the diagnosis of the hypochromic microcytic anemias, it is necessary to analyze a set of determinations, including hematological exam, iron status, electrophoretic profile, in some cases including relatives, and molecular analysis of the hemoglobinopathies.

Lead is a toxic heavy metal that has been extensively used in modern society, causing widespread environmental contamination, even in isolated parts of the world. There is now overwhelming evidence associating lead exposure with wideranging health effects, including reductions in intelligence scores, hyperactivity, shortened concentration spans, poor school performance, violent/aggressive behaviour, hearing loss, delayed onset of puberty, anaemia, and in severe cases, coma and death. In recent years consensus has been reached in respect of the absence of a threshold of safety for key health effects associated with lead exposure, and the permanent and irreversible nature of many of the health and social consequences of exposure to lead. The public health problem of environmental lead exposure has been widely investigated in developed countries such as the United States of America where, since the 1970s, policies and interventions have been followed by significant reductions in blood lead levels amongst children. In developing countries, and in African countries in particular, there is a relative dearth of information on the sources, mechanisms of exposure and blood lead distributions in children, and little action has been taken to protect children against lead poisoning. This study was undertaken to determine the current distribution of blood lead concentrations, and associated risk factors, amongst selected groups of first grade school children in the South African urban settings of Cape Town, Johannesburg 7 and Kimberley, a lead mining town (Aggeneys) and two rural towns in the Northern Cape province. A further objective of the study was to compare blood lead distributions determined in the current study with the findings of similar studies undertaken prior to the introduction in 1996 of unleaded petrol in South Africa. The results show that over the past decade, blood lead concentrations amongst first grade school children have declined considerably, but that large proportions of children, especially those living or attending school in impoverished areas, continue to have intolerably high blood lead concentrations, within a range that puts them at risk of detrimental health and social outcomes. The major sources of exposure to lead in the samples studied were leaded petrol, lead-based paint used to decorate homes and schools, lead solder used in “cottage industries” and other home-based lead-related activities, as well as the transfer of lead particles from lead-related work settings into homes. Recommendations for policy and relevant interventions for the South African context are discussed.

A falta de consenso na literatura acerca dos efeitos tóxicos do chumbo no sistema auditivo é notória, tanto em estudos clínicos quanto experimentais. Em adição, tem sido relatado que o ferro apresenta um efeito protetor na toxicidade cerebral causada pelo chumbo. Assim, estudos clínicos e bioquímicos têm sido realizados no intuito de compreender a relação entre o chumbo e o sistema auditivo, bem como identificar possíveis substâncias protetoras para a toxicidade deste metal. Neste sentido, no presente estudo verificou-se o processo maturacional do nervo auditivo e tronco encefálico, associado à análise proteômica da porção auditiva do tronco encefálico de ratos expostos a acetato de chumbo e suplementados com sulfato ferroso. O experimento foi realizado por seis semanas com 30 ratos (Rattus norvergicus, variedade Wistar) machos, recém-desmamados, divididos em seis grupos de cinco animais cada, sendo um controle, que recebeu água deionizada; dois grupos experimentais que receberam 100 mg/L de Pb(CH3COO)2 na água de beber, sendo administrado simultaneamente para um deles 20 mg/kg de FeSO4 a cada dois dias; dois grupos que receberam a dose de 400 mg/L de Pb (CH3COO)2 na água de beber, onde para um deles foi administrado simultaneamente 20 mg/kg de FeSO4 a cada dois dias e um grupo experimental que recebeu água deionizada e uma solução de 20 mg/kg de FeSO4 a cada dois dias. O processo maturacional do sistema auditivo foi verificado por meio da análise do Potencial Evocado Auditivo de Tronco Encefálico (PEATE) em dois momentos distintos, antes e depois da exposição ao chumbo. Os animais foram então sacrificados, coletado sangue e removido o tronco encefálico. A concentração de chumbo no sangue e tronco encefálico, apresentou um efeito dose-resposta, confirmado pela alta correlação entre a concentração nos dois compartimentos (r2=0,905, p<0,0001), tendo o sulfato ferroso reduzido a concentração de chumbo no sangue e no tecido, embora a diferença só tenha sido significativa para o sangue grupo que recebeu 100 mg/L de Pb(CH3COO)2). Com relação ao PEATE observou-se diferença estatisticamente significativa para o interpico I-II (p=0,049) nos grupos experimentais 100 mg/L Pb(CH3COO)2 e 400 mg/L Pb(CH3COO)2 e interpico I-IV, quando comparados os grupos 100 mg/L Pb(CH3COO)2 e 100 mg/L Pb(CH3COO)2 + FeSO4 (p=0,033). A análise proteômica apontou uma diminuição considerável no número de spots proteicos detectados em todos os grupos experimentais em relação ao controle, bem como uma redução na expressão do padrão proteico. Assim, o presente estudo reforça a hipótese do papel deletério do chumbo nas dosagens de 100 e 400 mg/L de Pb (CH3COO)2 na maturação do nervo auditivo e região do núcleo coclear, com possível efeito protetor do ferro. A análise proteômica do tronco encefálico de ratos demonstrou que o acetato de chumbo altera a expressão proteica desta estrutura, contudo o efeito protetor do sulfato ferroso não foi confirmado nas proteínas identificadas. / There is a lack of consensus in the literature about the toxic effects of lead in the auditory system, both in clinical and experimental studies. In addition to that, it has been reported that iron has a protective effect on brain toxicity caused by lead. Therefore, clinical and biochemical studies have been carried out to understand the relationship between Pb and the auditory function, as well as if the ferreous sulfate as an otoprotectant. In this study the maturational process of the auditory nerve and brainstem and the proteomic profile of the auditory portion of the brainstem of rats exposed to lead and supplemented with iron were evaluated. The experiment was carried out for six weeks with 30 wealing rats (Rattus norvegicus, Wistar), divided into six groups of five animals each: a control group that received deionized water; two experimental groups receiving 100 mg/L Pb(CH3COO)2 in drinking water, being given 20 mg/kg FeSO4 simultaneously to one of them every two days; two groups received 400 mg/LPb(CH3COO)2 in drinking water, where to one of them was given 20 mg/kg FeSO4 simultaneously every two days; and an experimental group that received deionized water and a solution of 20 mg/kg FeSO4 every two days. The maturational process of the auditory system was verified by analyzing the Brainstem Auditory-Evoked Potential (BAEP) at two different times, before and after lead exposure. The animals were sacrificed, their blood collected and brainstem removed. The concentration of lead in blood and brain stem showed a dose-response, confirmed by correlation between the concentration in the two compartments (rr2 = 0.905, p <0.0001). Ferreous sulfate reduced the levels of lead in blood and tissue, although the difference was only significant for blood (group receiving 100 mg/L Pb(CH3COO)2). Concerning to BEAP we observed a statistically significant difference for the interpeak I-II (p = 0.049) in the experimental groups 100 and 400 mg/L Pb(CH3COO)2 and for the interpeak I-IV, when groups 100 and 100 mg/L Pb(CH3COO)2 + FeSO4 were compared (p = 0.033). The proteomic analysis showed a considerable decrease in the number of protein spots detected in all experimental groups compared to control, as well as a reduction in the expression pattern of the proteins. Thus, the present study reinforces the hypothesis of deleterious role of Pb in dosages of 100 and 400 mg/L Pb(CH3COO)2 in the maturation of the auditory nerve and cochlear nucleus region, with a possible protective effect of ferreous sulfate. The proteomic analysis of the brainstem of rats showed that lead acetate alters protein expression of this structure. However, the protective effect of ferreous sulfate was not confirmed for the identified proteins.