RESUMEN
The morphogenesis of the head of vertebrates is a process that involves rapid growth and dynamic movements of various cell populations, including the neural crest cells (NCC). These pluripotent cells generated during neurulation have high proliferative and migratory capacity but xenobiotic agents can affect these migratory periods and cause congenital malformations. Lead (Pb) is the most common toxic metal in the environment and a potent teratogen that can affect growth and induce malformations. Despite the known toxic effects of Pb, there is a gap in knowledge about the impact of realistic concentrations of Pb at critical periods of early development. Here, we evaluated mortality, embryonic morphology, NCC migration, and the amount of Pb deposition in chicken embryos after 3 to 4 days of exposure. One of the most interesting observations in this study is that only about 34% of the injected Pb was present in the embryos after 4 days. We observed that exposure to Pb, even under low concentrations, increased mortality and the occurrence of malformations during embryonic development, especially in the cephalic region (CR). Although Pb was found widely distributed in the CR, no relation between its presence and the migration routes of cephalic NCC was observed. But the number of NCC and their migratory distance were reduced. These changes are consistent and explain the morphological anomalies described in this study, which also correlates with the morphofunctional abnormalities reported in the literature. Therefore, this study highlights the concern of exposure to low concentrations of this metal.
Asunto(s)
Intoxicación del Sistema Nervioso por Plomo/patología , Cresta Neural/patología , Anomalías Inducidas por Medicamentos/patología , Animales , Disponibilidad Biológica , Encéfalo/anomalías , Encéfalo/patología , Movimiento Celular , Embrión de Pollo , Desarrollo Embrionario/efectos de los fármacos , Plomo/metabolismo , Plomo/farmacocinética , Plomo/toxicidad , Intoxicación del Sistema Nervioso por Plomo/mortalidad , Morfogénesis , Nitratos/toxicidadRESUMEN
Developmentally-lead (Pb)-exposed rats showed an enhanced vulnerability to the stimulating and motivational effects of ethanol (EtOH). This is accompanied by differential activity of the brain EtOH-metabolizing enzymes catalase (CAT) and mitochondrial aldehyde dehydrogenase (ALDH2). Based on the theory that brain acetaldehyde accumulation is associated with the reinforcing properties of EtOH, this study sought to determine brain CAT and ALDH2 expression in limbic areas of control and Pb-exposed animals after voluntary EtOH intake. Thirty-five-day-old rats perinatally exposed to 220â¯ppm Pb were offered with water or increasing EtOH solutions (2-10% v/v) during 28 days until postnatal day (PND) 63. Once intake was stable, the animals were administered: 1) saline (SAL; test days 21-24 or 21-28, as corresponds), or 2) a CAT inhibitor: 3-amine 1, 2, 4-triazole (AT; 250â¯mg/kg intraperitoneally [i.p.], 5â¯h before the last eight EtOH intake sessions -test days 21-24 and 25-28), or 3) a CAT booster: 3-nitropropionic acid (3NPA; 20â¯mg/kg subcutaneously [s.c.], 45â¯min before the last four EtOH intake sessions -test days 25-28). Two additional groups were centrally-administered cyanamide (CY, an ALDH2 inhibitor, 0.3â¯mg i.c.v. immediately before the last four EtOH sessions, test days 25-28) or its corresponding vehicle (VEH). Lead exposure increased EtOH intake, an effect potentiated in both groups by 3NPA or CY pretreatments and reduced by AT, albeit selectivity in the Pb group. Catalase abundance in limbic areas parallels these observations in the Pb group, showing higher CAT expression in all areas after EtOH consumption respect to the controls, an effect prevented by AT administration. In contrast, ALDH2 expression was reduced in the Pb animals after EtOH intake, with CY potentiating this effect in all brain areas under study. Based on these results and on previous evidences, we suggest that Pb exposure promotes acetaldehyde accumulation in limbic regions, providing some insights into the mechanism of action that underlies the vulnerability to the excessive EtOH consumption reported in these animals.
Asunto(s)
Encéfalo/efectos de los fármacos , Etanol/farmacología , Intoxicación del Sistema Nervioso por Plomo/metabolismo , Consumo de Bebidas Alcohólicas/metabolismo , Consumo de Bebidas Alcohólicas/psicología , Aldehído Deshidrogenasa Mitocondrial/antagonistas & inhibidores , Aldehído Deshidrogenasa Mitocondrial/metabolismo , Animales , Encéfalo/enzimología , Encéfalo/metabolismo , Catalasa/metabolismo , Cianamida/farmacología , Femenino , Masculino , Nitrocompuestos/farmacología , Propionatos/farmacología , Ratas , Ratas WistarRESUMEN
Metals are a component of a variety of ecosystems and organisms. They can generally be divided into essential and nonessential metals. The essential metals are involved in physiological processes once the deficiency of these metals has been associated with diseases. Although iron, manganese, copper, and zinc are important for life, it has been evidenced that they are also involved in neuronal damage in many neurodegenerative disorders. Nonessential metals, which are metals without physiological functions, are present in trace or higher levels in living organisms. Occupational, environmental, or deliberate exposures to lead, mercury, aluminum, and cadmium are clearly correlated with the increase of toxicity and varied kinds of pathological situations. Actually, the field of neurotoxicology needs to satisfy two opposing demands: the testing of a growing list of chemicals and resource limitations and ethical concerns associated with testing using traditional mammalian species. Toxicological assays using alternative animal models may relieve some of this pressure by allowing testing of more compounds while reducing expenses and using fewer mammals. The nervous system is by far the more complex system in C. elegans. Almost a third of their cells are neurons (302 neurons versus 959 cells in adult hermaphrodite). It initially underwent extensive development as a model organism in order to study the nervous system, and its neuronal lineage and the complete wiring diagram of its nervous system are stereotyped and fully described. The neurotransmission systems are phylogenetically conserved from nematodes to vertebrates, which allows for findings from C. elegans to be extrapolated and further confirmed in vertebrate systems. Different strains of C. elegans offer a new perspective on neurodegenerative processes. Some genes have been found to be related to neurodegeneration induced by metals. Studying these interactions may be an effective tool to slow neuronal loss and deterioration.
Asunto(s)
Caenorhabditis elegans , Modelos Animales de Enfermedad , Intoxicación del Sistema Nervioso por Metales Pesados/etiología , Enfermedades Neurodegenerativas/inducido químicamente , Aluminio/envenenamiento , Animales , Intoxicación por Cadmio , Hierro/envenenamiento , Intoxicación del Sistema Nervioso por Plomo , Intoxicación por Manganeso , Intoxicación del Sistema Nervioso por Mercurio , Nanopartículas del Metal , Síndromes de Neurotoxicidad/etiología , Zinc/envenenamientoRESUMEN
This study investigated the toxicity of rats exposed to lead acetate (AcPb) during the second phase of brain development (8-12 days postnatal) in hematological and cerebral parameters. Moreover, the preventive effect of zinc chloride (ZnCl2) and N-acetylcysteine (NAC) was investigated. Pups were injected subcutaneously with saline (0.9% NaCl solution), ZnCl2 (27 mg/kg/day), NAC (5 mg/kg/day) or ZnCl2 plus NAC for 5 days (3rd-7th postnatal days), and with saline (0.9% NaCl solution) or AcPb (7 mg/kg/day) in the five subsequent days (8th-12th postnatal days). Animals were sacrificed 21 days after the last AcPb exposure. Pups exposed to AcPb presented inhibition of blood porphobilinogen-synthase (PBG-synthase) activity without changes in hemoglobin content. ZnCl2 pre-exposure partially prevented PBG-synthase inhibition. Regarding neurotoxicity biomarkers, animals exposed to AcPb presented a decrease in cerebrum acetylcholinesterase (AChE) activity and an increase in Pb accumulation in blood and cerebrum. These changes were prevented by pre-treatment with ZnCl2, NAC, and ZnCl2 plus NAC. AcPb exposure caused no alteration in behavioral tasks. In short, results show that AcPb inhibited the activity of two important enzymatic biomarkers up to 21 days after the end of the exposure. Moreover, ZnCl2 and NAC prevented the alterations induced by AcPb.
Asunto(s)
Acetilcisteína/uso terapéutico , Cerebro/efectos de los fármacos , Cloruros/uso terapéutico , Intoxicación del Sistema Nervioso por Plomo/prevención & control , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Compuestos de Zinc/uso terapéutico , Acetilcolinesterasa/metabolismo , Acetilcisteína/administración & dosificación , Animales , Animales Recién Nacidos , Biomarcadores/sangre , Biomarcadores/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Cerebro/enzimología , Cerebro/metabolismo , Cloruros/administración & dosificación , Cloruros/metabolismo , Cloruros/farmacocinética , Quimioterapia Combinada , Contaminantes Ambientales/sangre , Contaminantes Ambientales/metabolismo , Contaminantes Ambientales/toxicidad , Proteínas Ligadas a GPI/antagonistas & inhibidores , Proteínas Ligadas a GPI/metabolismo , Inyecciones Subcutáneas , Plomo/sangre , Plomo/metabolismo , Plomo/toxicidad , Intoxicación del Sistema Nervioso por Plomo/sangre , Intoxicación del Sistema Nervioso por Plomo/metabolismo , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Proteínas del Tejido Nervioso/metabolismo , Neuronas/enzimología , Neuronas/metabolismo , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/metabolismo , Fármacos Neuroprotectores/farmacocinética , Compuestos Organometálicos/administración & dosificación , Porfobilinógeno Sintasa/antagonistas & inhibidores , Porfobilinógeno Sintasa/sangre , Distribución Aleatoria , Ratas Wistar , Distribución Tisular/efectos de los fármacos , Toxicocinética , Compuestos de Zinc/administración & dosificación , Compuestos de Zinc/metabolismo , Compuestos de Zinc/farmacocinéticaRESUMEN
Lead (Pb) induces adverse effects when it chronically accumulates in the body, including effects on the nervous and cardiovascular systems. Wistar rats were exposed to lead acetate for 30 days (first dose 4 µg/100 g followed by 0.05 µg/100 g/day, i.m.) to investigate the cardiovascular system impact on the autonomic control. The femoral artery and vein were catheterised to perform hemodynamic evaluations in awake rats: heart rate variability (HRV), baroreflex sensitivity, cardiopulmonary reflex and hemodynamic responses to vagal and sympathetic pharmacological blockade. Rats exposed to Pb exhibited a higher blood pressure and reduced HRV in the time domain when compared to the saline-injected group. Spectral analysis of the HRV in the frequency-domain showed an augmented low-frequency component of the spectrum. Methylatropine and atenolol administration suggest increased sympathetic tone and reduced vagal tone on the control of heart rate. Chronic Pb exposure decreased the sensitivity of the baroreflex without significantly changing the cardiopulmonary reflex. This study demonstrated for the first time in an animal model of a controlled, low-dose chronic lead exposure that cardiovascular changes, such as arterial hypertension, are accompanied by impaired autonomic control of the cardiovascular system, as characterised by reduced baroreflex sensitivity and a sympathovagal imbalance.
Asunto(s)
Barorreflejo , Presión Sanguínea , Sistema Cardiovascular/inervación , Frecuencia Cardíaca , Intoxicación del Sistema Nervioso por Plomo/fisiopatología , Compuestos Organometálicos , Sistema Nervioso Simpático/fisiopatología , Nervio Vago/fisiopatología , Animales , Modelos Animales de Enfermedad , Intoxicación del Sistema Nervioso por Plomo/etiología , Ratas Wistar , Factores de TiempoRESUMEN
OBJECTIVES: Lead exposure remains a significant environmental problem; lead is neurotoxic, especially in developing humans. In Mexico, lead in human blood is still a concern. Historically, much of the lead exposure is attributed to the use of handcrafted clay pottery for cooking, storing and serving food. However, experimental cause-and-effect demonstration is lacking. The present study explores this issue with a prospective experimental approach. METHODS: We used handcrafted clay containers to prepare and store lemonade, which was supplied as drinking water to pregnant rats throughout the gestational period. RESULTS AND DISCUSSION: We found that clay pots, jars, and mugs leached on average 200â µg/l lead, and exposure to the lemonade resulted in 2.5â µg/dl of lead in the pregnant rats' blood. Neonates also showed increased lead content in the hippocampus and cerebellum. Caspase-3 activity was found to be statistically increased in the hippocampus in prenatally exposed neonates, suggesting increased apoptosis in that brain region. Glazed ceramics are still an important source of lead exposure in Mexico, and our results confirm that pregnancy is a vulnerable period for brain development.
Asunto(s)
Silicatos de Aluminio/química , Utensilios de Comida y Culinaria , Exposición Dietética/efectos adversos , Contaminación de Alimentos , Almacenamiento de Alimentos/instrumentación , Intoxicación del Sistema Nervioso por Plomo/etiología , Plomo/toxicidad , Animales , Animales Recién Nacidos , Conducta Animal/efectos de los fármacos , Cerebelo/efectos de los fármacos , Cerebelo/metabolismo , Citrus/química , Arcilla , Femenino , Jugos de Frutas y Vegetales/efectos adversos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Humanos , Plomo/sangre , Plomo/metabolismo , Intoxicación del Sistema Nervioso por Plomo/sangre , Masculino , Exposición Materna/efectos adversos , México , Embarazo , Distribución Aleatoria , Ratas Wistar , Distribución Tisular , ToxicocinéticaRESUMEN
O chumbo é um metal utilizado amplamente na indústria automotiva, bem como na produção de soldas, tintas, cerâmicas e na manufatura de baterias. Pode ser absorvido pelo corpo humano, principalmente por via respiratória, através de vapores. Quando em contato com hemácias, liga-se avidamente e se distribui por todo organismo, causando a doença ocupacional, chamada saturnismo. O principal sistema afetado é o sistema nervoso central, com sintomas de encefalopatia de variados graus. Assim, trabalhadores que manipulam essa substância devem utilizar proteção adequada. No presente trabalho, são relatados dois casos de intoxicação aguda pelo chumbo, associadas à exposição ocupacional.
Lead is a metal that is widely used in the automotive industry as well as in the production of solders, paints, ceramics and in the manufacturing of batteries. It can be absorbed by the human body, mainly by the respiratory route, through vapors. When in contact with red blood cells, lead binds avidly and is distributed throughout the body, causing the occupational disease called lead poisoning. The main system affected is the central nervous system with symptoms of encephalopathy, in varying degrees. Thus, workers who handle this substance should use adequate protection. In this paper we report two cases of acute poisoning by lead associated with occupational exposure.
Asunto(s)
Humanos , Exposición Profesional , Intoxicación del Sistema Nervioso por PlomoRESUMEN
O chumbo (Pb) é um metal pesado que pode ocasionar alterações nos sistemas nervoso central (SNC) e auditivo. Faltam estudos que demonstrem tais alterações clínicas, em conjunto com as alterações bioquímicas e morfológicas em cérebro de ratos expostos ao Pb. Tem sido relatado que o ferro (Fe) tem um efeito protetor na toxicidade cerebral causada pelo Pb. O objetivo deste estudo foi avaliar a atividade elétrica cerebral, analisar a concentração de Pb no sangue e tecido cerebral, e observar o aspecto morfológico do cérebro de ratos intoxicados por Pb, submetidos à suplementação com Fe ou não. Foi realizado um projeto piloto utilizando 20 ratos machos recém-desmamados (Rattus norvegicus, variedade Wistar), que foram divididos em 5 grupos, sendo um controle e 4 experimentais (n=4/grupo). Nos grupos experimentais, os animais receberam por 6 semanas acetato de chumbo em água de beber nas concentrações de 100 mg/L e 400 mg/L de Pb, e em dois destes grupos houve administração simultânea de 20 mg/Kg de FeSO4 a cada 2 dias, por gavagem gástrica, e no outro não. O grupo controle recebeu, água deionizada. Após estabelecida a relação entre o Pb administrado e a dosagem deste no sangue (10 μgPb/dL e 30 μgPb/dL para as dosagens 100 e 400 mg/L de Pb, respectivamente), o experimento foi realizado com 30 ratos recém-desmamados divididos em 6 grupos (n=5/grupo). Os cinco primeiros foram idênticos aos empregados no estudo piloto, incluindo um grupo no qual os animais receberam água deionizada e 20 mg/Kg FeSO4 por gavagem gástrica a cada 2 dias, por 6 semanas. Após o período experimental, foi realizado o Potencial Evocado Auditivo Cortical (PEAC) com a análise da latência dos componentes P1, N1 e P2. Após a eutanásia, o cérebro dos animais foi removido, submetido ao processamento histológico (hematoxilina e eosina) e analisado ao microscópio óptico. Os dados foram analisados por ANOVA/Tukey, Kruskal-Wallis/Dunn e regressão linear (p<0,05). Foi observada uma dose-resposta...
Lead (Pb) is a heavy metal that may cause alterations in the central nervous system (CNS) and auditory system. There is lack of studies demonstrating these clinical alterations, combined to the biochemical and morphological alterations in the brain of rats exposed to Pb. It has been reported that iron (Fe) has a protective effect on the brain toxicity caused by Pb. This study evaluated the electrical brain activity, analyzed the Pb concentration in blood and brain tissue, and observed the morphological aspect of the brain in rats intoxicated by Pb, submitted or not to Fe supplementation. A pilot study was conducted on 20 recently weaned male rats (Rattus norvegicus, Wistar type) divided in 5 groups, being one control and 4 experimental (n=4/group). In the experimental groups, the animals received lead acetate in drinking water for 6 weeks at concentrations of 100 mg/L and 400 mg/L of Pb, and in two of these groups there was simultaneous administration of 20 mg/Kg of FeSO4 at every 2 days, by gastric gavage. The control group received deionized water. After establishing the relationship between the administered Pb and its concentration in blood (10 μgPb/dL and 30 μgPb/dL for concentrations of 100 and 400 mg/L of Pb, respectively), the study was conducted on 30 recently weaned rats divided in 6 groups (n=5/group). The five first groups were identical to those used in the pilot study, including one group in which the animals received deionized water and 20 mg/Kg FeSO4 by gastric gavage at every 2 days, for 6 weeks. After the study period, the Cortical Auditory Evoked Potential (CAEC) was applied for analysis of latency of the components P1, N1 and P2. The animals were killed, their brains were removed and submitted to histological processing (hematoxylin and eosin) for light microscopy analysis. Data were analyzed by the ANOVA/Tukey, Kruskal-Wallis/Dunn and linear regression tests (p<0.05). A dose- response relationship was observed in the Pb concentration...
Asunto(s)
Animales , Masculino , Ratas , Cerebro , Potenciales Evocados Auditivos del Tronco Encefálico , Hierro de la Dieta/uso terapéutico , Intoxicación del Sistema Nervioso por Plomo/terapia , Plomo/sangre , Ratas Wistar , Reproducibilidad de los Resultados , Resultado del TratamientoRESUMEN
O chumbo (Pb) é um metal pesado que pode ocasionar alterações nos sistemas nervoso central (SNC) e auditivo. Faltam estudos que demonstrem tais alterações clínicas, em conjunto com as alterações bioquímicas e morfológicas em cérebro de ratos expostos ao Pb. Tem sido relatado que o ferro (Fe) tem um efeito protetor na toxicidade cerebral causada pelo Pb. O objetivo deste estudo foi avaliar a atividade elétrica cerebral, analisar a concentração de Pb no sangue e tecido cerebral, e observar o aspecto morfológico do cérebro de ratos intoxicados por Pb, submetidos à suplementação com Fe ou não. Foi realizado um projeto piloto utilizando 20 ratos machos recém-desmamados (Rattus norvegicus, variedade Wistar), que foram divididos em 5 grupos, sendo um controle e 4 experimentais (n=4/grupo). Nos grupos experimentais, os animais receberam por 6 semanas acetato de chumbo em água de beber nas concentrações de 100 mg/L e 400 mg/L de Pb, e em dois destes grupos houve administração simultânea de 20 mg/Kg de FeSO4 a cada 2 dias, por gavagem gástrica, e no outro não. O grupo controle recebeu, água deionizada. Após estabelecida a relação entre o Pb administrado e a dosagem deste no sangue (10 μgPb/dL e 30 μgPb/dL para as dosagens 100 e 400 mg/L de Pb, respectivamente), o experimento foi realizado com 30 ratos recém-desmamados divididos em 6 grupos (n=5/grupo). Os cinco primeiros foram idênticos aos empregados no estudo piloto, incluindo um grupo no qual os animais receberam água deionizada e 20 mg/Kg FeSO4 por gavagem gástrica a cada 2 dias, por 6 semanas. Após o período experimental, foi realizado o Potencial Evocado Auditivo Cortical (PEAC) com a análise da latência dos componentes P1, N1 e P2. Após a eutanásia, o cérebro dos animais foi removido, submetido ao processamento histológico (hematoxilina e eosina) e analisado ao microscópio óptico. Os dados foram analisados por ANOVA/Tukey, Kruskal-Wallis/Dunn e regressão linear (p<0,05). Foi observada uma dose-resposta...
Lead (Pb) is a heavy metal that may cause alterations in the central nervous system (CNS) and auditory system. There is lack of studies demonstrating these clinical alterations, combined to the biochemical and morphological alterations in the brain of rats exposed to Pb. It has been reported that iron (Fe) has a protective effect on the brain toxicity caused by Pb. This study evaluated the electrical brain activity, analyzed the Pb concentration in blood and brain tissue, and observed the morphological aspect of the brain in rats intoxicated by Pb, submitted or not to Fe supplementation. A pilot study was conducted on 20 recently weaned male rats (Rattus norvegicus, Wistar type) divided in 5 groups, being one control and 4 experimental (n=4/group). In the experimental groups, the animals received lead acetate in drinking water for 6 weeks at concentrations of 100 mg/L and 400 mg/L of Pb, and in two of these groups there was simultaneous administration of 20 mg/Kg of FeSO4 at every 2 days, by gastric gavage. The control group received deionized water. After establishing the relationship between the administered Pb and its concentration in blood (10 μgPb/dL and 30 μgPb/dL for concentrations of 100 and 400 mg/L of Pb, respectively), the study was conducted on 30 recently weaned rats divided in 6 groups (n=5/group). The five first groups were identical to those used in the pilot study, including one group in which the animals received deionized water and 20 mg/Kg FeSO4 by gastric gavage at every 2 days, for 6 weeks. After the study period, the Cortical Auditory Evoked Potential (CAEC) was applied for analysis of latency of the components P1, N1 and P2. The animals were killed, their brains were removed and submitted to histological processing (hematoxylin and eosin) for light microscopy analysis. Data were analyzed by the ANOVA/Tukey, Kruskal-Wallis/Dunn and linear regression tests (p<0.05). A dose- response relationship was observed in the Pb concentration...
Asunto(s)
Animales , Masculino , Ratas , Cerebro , Potenciales Evocados Auditivos del Tronco Encefálico , Hierro de la Dieta/uso terapéutico , Intoxicación del Sistema Nervioso por Plomo/terapia , Plomo/sangre , Ratas Wistar , Reproducibilidad de los Resultados , Resultado del TratamientoRESUMEN
Esta publicação reúne estudos abrangentes sobre as fontes e distribuição do chumbo no ambiente, desafios ao controle da exposição humana, e resultados das investigações realizadas nas principais áreas contaminadas por chumbo no Brasil. Reúne textos de pesquisadores do Brasil, Uruguai e Portugal, abordando também aspectos sobre efeitos do chumbo no organismo humano, como danos ao sistema nervoso central e outros agravos à saúde
Asunto(s)
Humanos , Plomo/efectos adversos , Plomo/toxicidad , Ambiente , Ambiente , Intoxicación por Plomo/prevención & control , Intoxicación del Sistema Nervioso por Plomo , Contaminación Costera/efectos adversos , Sistemas de Información Geográfica/estadística & datos numéricosRESUMEN
We investigated the antioxidant potential of gallic acid (GA), a natural compound found in vegetal sources, on the motor and oxidative damages induced by lead. Rats exposed to lead (50 mg/kg, i.p., once a day, 5 days) were treated with GA (13.5mg/kg, p.o.) or EDTA (110 mg/kg, i.p.) daily, for 3 days. Lead exposure decreased the locomotor and exploratory activities, reduced blood ALA-D activity, and increased brain catalase (CAT) activity without altering other antioxidant defenses. Brain oxidative stress (OS) estimated by lipid peroxidation (TBARS) and protein carbonyl were increased by lead. GA reversed the motor behavior parameters, the ALA-D activity, as well as the markers of OS changed by lead exposure. CAT activity remained high, possibly as a compensatory mechanism to eliminate hydroperoxides during lead poisoning. EDTA, a conventional chelating agent, was not beneficial on the lead-induced motor behavior and oxidative damages. Both GA (less) and EDTA (more) reduced the lead accumulation in brain tissue. Negative correlations were observed between the behavioral parameters and lipid peroxidation and the lead levels in brain tissue. In conclusion, GA may be an adjuvant in lead exposure, mainly by its antioxidant properties against the motor and oxidative damages resulting from such poisoning.
Asunto(s)
Antioxidantes/farmacología , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Ácido Gálico/farmacología , Intoxicación del Sistema Nervioso por Plomo/prevención & control , Actividad Motora/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Encéfalo/metabolismo , Catalasa/metabolismo , Quelantes/farmacología , Modelos Animales de Enfermedad , Ácido Edético/farmacología , Conducta Exploratoria/efectos de los fármacos , Plomo , Intoxicación del Sistema Nervioso por Plomo/metabolismo , Intoxicación del Sistema Nervioso por Plomo/fisiopatología , Intoxicación del Sistema Nervioso por Plomo/psicología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Nitratos , Porfobilinógeno Sintasa/metabolismo , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
Lead poisoning has been reportedly linked to a high risk of learning disabilities, aggression and criminal offenses. To study the association between lead exposure and antisocial/delinquent behavior, a cross-sectional study was conducted with 173 Brazilian youths aged 14-18 and their parents (n=93), living in impoverished neighborhoods of Bauru-SP, with high criminality indices. Self-Reported Delinquency (SRD) and Child Behavior Checklist (CBCL) questionnaires were used to evaluate delinquent/antisocial behavior. Body lead burdens were evaluated in surface dental enamel acid microbiopsies. The dental enamel lead levels (DELL) were quantified by graphite furnace atomic absorption spectrometry (GFAAS) and phosphorus content was measured using inductively coupled plasma optical emission spectrometry (ICP-OES). Logistic regression was used to identify associations between DELL and each scale defined by CBCL and SRD scores. Odd ratios adjusted for familial and social covariates, considering a group of youths exposed to high lead levels (>or=75 percentile), indicated that high DELL is associated with increased risk of exceeding the clinical score for somatic complaints, social problems, rule-breaking behavior and externalizing problems (CI 95%). High DELL was not found to be associated with elevated SRD scores. In conclusion, our data support the hypothesis that high-level lead exposure can trigger antisocial behavior, which calls for public policies to prevent lead poisoning.
Asunto(s)
Trastorno de Personalidad Antisocial/inducido químicamente , Trastorno de Personalidad Antisocial/epidemiología , Esmalte Dental/metabolismo , Exposición a Riesgos Ambientales/efectos adversos , Intoxicación del Sistema Nervioso por Plomo/epidemiología , Plomo/metabolismo , Adolescente , Trastorno de Personalidad Antisocial/fisiopatología , Biomarcadores/análisis , Biomarcadores/metabolismo , Brasil/epidemiología , Comorbilidad , Psicología Criminal , Estudios Transversales , Esmalte Dental/química , Femenino , Humanos , Plomo/análisis , Intoxicación del Sistema Nervioso por Plomo/diagnóstico , Intoxicación del Sistema Nervioso por Plomo/fisiopatología , Masculino , Fósforo/análisis , Fósforo/metabolismo , Áreas de Pobreza , Factores Socioeconómicos , Espectrofotometría Atómica , Encuestas y CuestionariosRESUMEN
Lead intoxication is a serious occupational disease that constitutes a major public health problem. Lead, a heavy metal, has been used by humans for many technological purposes, which is the main reason for its widespread distribution. The toxic mechanisms of lead on the molecular machinery of living organisms include metal transport, energy metabolism, diverse enzymatic processes, genetic regulation, and membrane ionic channels and signaling molecules. Since lead is able to cross the blood-brain barrier it may cause neurotoxicity. Creatine kinase and pyruvate kinase are two thiol-containing enzymes that exert a key role for cellular energy homeostasis in brain. Our main objective was to investigate the in vitro effect of lead on pyruvate kinase and creatine kinase activities of extracts and subcellular fractions from the brain cortex of rats in the presence or not of thiol-protecting substances such as glutathione and cysteamine. The results showed that lead inhibited the two enzyme activities and the thiol-protecting substances prevented their inhibition. These results suggest that lead inhibits creatine kinase and pyruvate kinase activity by interaction with their thiol groups. Therefore, lead may disrupt energy homeostasis and this effect may contribute to the neurological dysfunction found in lead exposed individuals.
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Corteza Cerebral/enzimología , Creatina Quinasa/antagonistas & inhibidores , Inhibidores Enzimáticos , Intoxicación del Sistema Nervioso por Plomo/enzimología , Plomo/toxicidad , Piruvato Quinasa/antagonistas & inhibidores , Animales , Corteza Cerebral/efectos de los fármacos , Cisteamina/farmacología , Citosol/efectos de los fármacos , Citosol/enzimología , Relación Dosis-Respuesta a Droga , Glutatión/farmacología , Masculino , Mitocondrias/efectos de los fármacos , Mitocondrias/enzimología , Sustancias Protectoras/farmacología , Ratas , Ratas Wistar , Fracciones Subcelulares/efectos de los fármacos , Fracciones Subcelulares/enzimología , Compuestos de Sulfhidrilo/metabolismoRESUMEN
Em praticamente todo tipo de exposição a chumbo, considerando a duração a curto ou longo prazos, em altas ou baixas concentrações, o órgão crítico alvo é sempre o cérebro, promovendo sinais e sintomas tais como, cefaléia, perda de memória, perda da concentração e atenção em tarefas corriqueiras, alterações de humor, com irritabilidade, depressão, insônia (ou sonolência excessiva). Alguns estudos têm demonstrado evidências de que, mesmo em níveis de exposição relativamente baixos, o Chumbo(Pb) detectável foi associado com déficit nas funções cognitivas, intelectuais e funcionamento executivo, comportamentos antissociais, e transtorno de déficit de atenção e hiperatividade déficit. Outros estudos foram capazes de demonstrar que a redução dos níveis de exposição ao Pb pode ser responsável pela redução dos níveis de impulsividade, agressividade e criminalidade em adolescentes. Por fim evidências suportam a hipótese de que as exposições ao Pb podem perturbar o desenvolvimento do SNC, e estão associadas com esquizofrenia e transtornos de psicoses relacionados. Alguns estudos que relatam uma relação estrutura-função e psicopatologia são abordados nesta revisão.
In virtually every type of exposure to lead, considering the short term or long term in high or low concentrations, the critical target organ is always the brain, encouraging signs and symptoms such as headache, memory loss, loss of concentration and attention in tasks occurring, changes in mood, with irritability, depression, insomnia (or excessive sleepiness). Several studies have shown evidence that, evenat relatively low exposure levels, lead (Pb) was detected associated with deficits in cognitive functions, intellectual and executive functioning, personality disorder like antisocial behavior and attention-deficithy peractivity deficit disorder. Other studies were able to demonstrate that reducing the levels of exposureto Pb can be responsible for reducing levels of impulsivity, aggression and crime among adolescents. Finally evidence supporting the hypothesis that exposure to Pb can disrupt the development of the central nervous system and are associated with schizophrenia and related psychotic disorders. Some studies that reported a relationship between structure-function and psychopathology are are also discussed in this review.
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Humanos , Plomo/toxicidad , Intoxicación del Sistema Nervioso por Plomo , Manifestaciones Neuroconductuales , Psicopatología , Grado de Concentración de Radionúclido , Trastornos MentalesRESUMEN
O presente trabalho consiste em uma revisão bibliográfica a respeito da exposição ao chumbo em baixas concentrações e seus efeitos em crianças. Apesar do limite tolerado de chumbo no sangue, fixado pela OMS em 10mg/dl, diversos estudos transversais e longitudinais têm apontado que doses abaixo desse limite também geram consequências negativas no desenvolvimento infantil. Na primeira infância, observa-se correlação entre exposição pré-natal ao chumbo e déficits cognitivos; e correlação inversa entre níveis correntes de chumbo no sangue e desempenho cognitivo. A exposição a baixos níveis de chumbo na primeira infância também foi associada a prejuízo no desempenho cognitivo e escolar anos depois. Exposição ao chumbo na fase escolar tem sido associada a problemas no desempenho acadêmico, na atenção e em funções neuropsicológicas diversas. Estudos recentes detectaram ligação entre baixa exposição ao chumbo e problemas de comportamento na criança. A evidência acumulada indica risco de prejuízo neuropsicológico e adaptativo em crianças expostas abaixos níveis de chumbo. Os danos são maiores em concentrações muito baixas, inferiores ao nível tolerado pela OMS, indicando a necessidade de trabalhos de prevenção.
This is a literature review about low-level lead exposure and its effects on children. Although the current World Health Organization blood level of concern stands at 10 mg/dL, numerous prospective and cross sectional studies have extended the association of blood lead and developmental impairment to lower levels of lead exposure. During early childhood, there is a positive association between prenatal low-level-lead exposure and cognitive deficits. There is also a negative correlation between current blood lead level and cognitive performance. Low-level lead exposure in early childhood predicts cognitive and academic under achievement years later. During the school years, low-level lead exposure is concurrently associated to impairments in academic achievement, attention, and several neuropsychological functions. Recent investigations have detected a relationship between lead exposure and behavior problems in children. The evidence points to the neuropsychological and adaptive risks of low-level lead exposure during early and middle childhood and suggests that there is no safety margin at existing exposures. Harm is greater in very small concentrations, below the current WHO level of concern, thus indicating the need for prevention efforts.
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Humanos , Masculino , Femenino , Niño , Rendimiento Escolar Bajo , Plomo/efectos adversos , Plomo/toxicidad , Intoxicación del Sistema Nervioso por Plomo , Manifestaciones Neuroconductuales , NeuropsicologíaRESUMEN
This study was designed to assess the utility of two psychometric tests with putative minimal cultural bias for use in field screening of lead (Pb)-exposed Ecuadorian Andean workers. Specifically, the study evaluated the effectiveness in Pb-exposed adolescents and young adults of a nonverbal reasoning test standardized for younger children, and compared the findings with performance on a test of auditory memory. The Raven Coloured Progressive Matrices (RCPM) was used as a test of nonverbal intelligence, and the Digit Span subtest of the Wechsler IV intelligence scale was used to assess auditory memory/attention. The participants were 35 chronically Pb-exposed Pb-glazing workers, aged 12-21 yr. Blood lead (PbB) levels for the study group ranged from 3 to 86 microg/dl, with 65.7% of the group at and above 10 microg/dl. Zinc protoporphyrin heme ratios (ZPP/heme) ranged from 38 to 380 micromol/mol, with 57.1% of the participants showing abnormal ZPP/heme (>69 micromol/mol). ZPP/heme was significantly correlated with PbB levels, suggesting chronic Pb exposure. Performance on the RCPM was less than average on the U.S., British, and Puerto Rican norms, but average on the Peruvian norms. Significant inverse associations between PbB/ZPP concentrations and RCPM standard scores using the U.S., Puerto Rican, and Peruvian norms were observed, indicating decreasing RCPM test performance with increasing PbB and ZPP levels. RCPM scores were significantly correlated with performance on the Digit Span test for auditory memory. Mean Digit Span scale score was less than average, suggesting auditory memory/attention deficits. In conclusion, both the RCPM and Digit Span tests were found to be effective instruments for field screening of visual-spatial reasoning and auditory memory abilities, respectively, in Pb-exposed Andean adolescents and young adults.
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Cognición/efectos de los fármacos , Intoxicación del Sistema Nervioso por Plomo/psicología , Pruebas Neuropsicológicas , Adolescente , Atención/efectos de los fármacos , Niño , Ecuador , Femenino , Hemo/metabolismo , Humanos , Plomo/sangre , Intoxicación del Sistema Nervioso por Plomo/diagnóstico , Masculino , Memoria/efectos de los fármacos , Exposición Profesional , Protoporfirinas/sangre , Psicometría , Percepción Espacial/efectos de los fármacos , Percepción Visual/efectos de los fármacos , Escalas de Wechsler , Adulto JovenRESUMEN
A exposição ao chumbo ainda permanece como um sério problema de saúde pública, especialmente nos países em desenvolvimento como o Brasil. Apesar do número crescente de estudos mostrando déficits neurocomportamentais em indivíduos expostos ocupacionalmente ao chumbo, os mecanismos envolvidos com a manifestação destes transtornos permanecem pouco conhecidos. Desta forma, o uso de modelos animais abre grandes possibilidades, não somente de investigação dos mecanismos biológicos envolvidos com a toxicidade do chumbo, mas também na elaboração de estratégias para proteção e/ou reversão dos seus efeitos. Portanto, o objetivo central deste trabalho foi avaliar o potencial do comportamento rotacional, medido em testes de nado livre, como um modelo em roedores para estudo dos efeitos neurocomportamentais da exposição ao chumbo durante a vida adulta. Para tanto, foram realizados três estudos. No primeiro, avaliamos os efeitos da exposição subcrônica (60-90 dias) ao chumbo sobre a atividade locomotora no teste de nado livre e em um teste tradicionalmente utilizado para avaliar a ação de substâncias neurotóxicas sobre a locomoção, o campo aberto. Enquanto no campo aberto não foram encontradas diferenças significativas entre o grupo exposto e o grupo controle, no teste de nado livre, os animais expostos ao chumbo apresentaram maior atividade natatória e menor quantidade de alternâncias espontâneas no sentido de natação que o grupo controle. No segundo estudo, observamos que a magnitude dos efeitos do chumbo no teste de nado livre variou em função da consistência da lateralidade, sendo os resultados mais pronunciados no grupo de animais não consistentes (com menor lateralidade). Nos dois estudos, os efeitos do chumbo foram independentes do nível de chumbo em sangue (PbS) dos animais expostos. No terceiro estudo, mostramos um aumento dos níveis de glutationa oxidada no cérebro somente no grupo de animais com PbS acima de 60 ug/dL...
Lead exposure continues to be a serious public health problem, particularly in developing countries such as Brazil. Despite the increasing number of studies showing neurobehavioral deficits in people occupationally exposed to lead, the mechanisms involved in the manifestation of these problems remain largely unknown. In this sense, the use of animal models opens up the possibility of not only investigating the biological mechanisms associated with lead toxicity but also of elaborating strategies aiming at protecting individuals against its ill effects or even reversing those that already present. Therefore, the main objective of the present work was to assess the potential of the rotatory behavior in the free-swimming test as a rodent model for studying of the neurobehavioral effects adult life lead exposure. In the first study, we analyzed the effect of subchronic lead exposure on motor activity in the free-swimming test and in open-field test, which has been traditionally used to assess the effects of toxic substances on locomotion. While no significant differences were observed between the exposed and control groups in the open-field, in the free-swimming test, lead exposed animals displayed increased natatory activity and fewer spontaneous alterations in the direction of locomotion in comparison with the control group. In the second study, we observed that the magnitude of the effects of lead exposure varied as a function of the consistency of the lateralization, being the results more pronounced in inconsistent animals (lesser degree of lateralization). In both studies, the effects of lead were not dependent on blood levels of lead exposed animals. In the third study, we demonstrated a significant increase in the levels of oxidized glutathione in the brain (indicative of oxidative stress) only in the group of animals that had lead levels above 60 ug/dL. Based in these results, we can conclude that: 1) Rotatory behavior in the free-swimming test...
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Animales , Adulto , Ratones , Actividad Motora , Conducta Animal , Plomo/efectos adversos , Plomo/toxicidad , Glutatión/farmacología , Intoxicación del Sistema Nervioso por Plomo , Lateralidad Funcional , Lateralidad Funcional/fisiología , Manifestaciones Neuroconductuales , Natación/fisiologíaRESUMEN
Introdução- A intoxicação por chumbo é um conhecido problema de saúde pública e o envenenamento por este metal pode causar danos a vários órgãos, especialmente ao Sistema Nervoso Central de crianças em desenvolvimento. Objetivo geral- estudar a associação entre exposição a chumbo e comportamento anti-social (CAS) em adolescentes brasileiros. Objetivos específicos: a) analisar a associação entre exposição a chumbo e CAS / cometimento de atos infracionais (CAI); b) estudar potenciais fontes de exposição domiciliar a chumbo que mais estão associadas a altas concentrações de chumbo no esmalte dentário (CCED) e; c) avaliar o impacto de alterações metodológicas na técnica de microbiópsia ácida de esmalte dentário superficial (MAEDS) sobre CCED e profundidade da bíópsia. Métodos- Um estudo transversal foi conduzido com 173 jovens (Bauru, SP). MAEDS foram realizadas nestes jovens por dois diferentes protocolos metodológicos. Além disso, questionários sobre comportamento dos adolescentes e exposição a possíveis fontes de contaminação por chumbo foram aplicados a pais e adolescentes. Análises de regressão logística, testes de Wilcoxon e testes pareados foram aplicados aos dados. Resultados- Odd ratios ajustados para covariáveis indicaram que alta CCED está associada a risco aumentado de exceder o escore clínico para queixas somáticas, problemas sociais, comportamento de quebrar regras e problemas externalizantes (IC 95 por cento). Alta CCED não foi associado com escores elevados de CAI. Os fatores de risco mais associados com alta CCED foram residir em área contaminada ou até 2 km da área contaminada e trabalhar na fabricação de tintas, pigmentos, cerâmicas ou baterias. A profundidade da biópsia, calculada pela fórmula da altura do cilindro, para um dos protocolos, levou a resultados errôneos de profundidade da biópsia, confirmados por testes de perfilometria. Conclusões- A exposição a altos níveis de chumbo parece disparar o estabelecimento de CAS, o que alerta para...
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Biopsia/instrumentación , Trastorno de la Conducta , Esmalte Dental , Salud Ambiental , Intoxicación del Sistema Nervioso por Plomo , Biomarcadores , Oportunidad Relativa , Factores de Riesgo , Trastorno de la Conducta Social , ViolenciaRESUMEN
Lead intoxication affects the central nervous system and produces structural disorders and behavioral deficits in several animal species. Although lead neurotoxicity is a well-reported phenomenon, studies on the developmental neurotoxicity induced by this metal in avian are scarce. The aim of this study was to evaluate how a single dose of 28 mug lead acetate administered into the yolk sac on the fifth incubation day of Gallus domesticus can affect the behavior and the brain tissue in the first postnatal week. Several behavioral tests, mainly those related to the motor and exploratory functions were evaluated at fifth and sixth postnatal days (PN). The lead deposition into mesencephalon and cerebellum was investigated by autometallography (AMG) method. Congenital anomalies, as failure on closure of body's ventral midline and leg dysfunction, were observed in treated chicks. During the first postnatal week, inactivity and anomalous movements were significantly high in lead treated chicks in comparison to control animals. Lead impregnation was observed in both mesencephalon and cerebellum and the cerebellar molecular layer presented higher lead deposition in comparison to granular layer and Purkinje cells. Our results indicate that the in ovo exposure to lead induces important deficits on motor behavior of chicks during the first postnatal week and such phenomena are related to lead deposition in the cerebellar tissue during embryonic development. The proposed exposure schedule represents an interesting experimental approach for studding behavioral and cellular mechanisms related to lead-induced developmental neurotoxicity.