Continuous exercise training and curcumin attenuate changes in brain-derived neurotrophic factor and oxidative stress induced by lead acetate in the hippocampus of male rats.

CONTEXT: For many years it has been known that lead is life-threatening, not only as an air pollutant but also because of it has been associated with several conditions including neurodegenerative disease. Curcumin (the principal curcuminoid found in turmeric) has demonstrated potent antioxidant properties. OBJECTIVE: We investigated neuroprotective effects of endurance exercise and/or curcumin on lead acetate-induced neurotoxicity in the rat hippocampus. MATERIALS AND METHODS: Forty male Wistar rats were randomly divided into five groups: 1) lead acetate, 2) curcumin, 3) training, 4) training + curcumin, and 5) control. The rats in the training groups performed treadmill running five times a week for 8 weeks (15-22 m/min, 25-64 min). All groups except control received lead acetate (20 mg/kg), whereas the control group received curcumin solution (ethyl oleate). In addition, the curcumin and training + curcumin groups received curcumin solution (30 mg/kg) intraperioneally. RESULTS: Lead acetate resulted in a significantly increase in the malondialdehyde (MDA) in plasma (72%), but not significant in hippocampus (59%). In addition, it led to significantly decreased brain-derived neurotrophic factor in hippocampus (17%) and total antioxidant capacity (27%), as compared to control group. Treadmill running, curcumin supplementation or both resulted in a significant decrease in hippocampus MDA (17, 20, 31%, respectively) and plasma MDA (60, 22, 71%) and also, significantly increased brain-derived neurotrophic factor (76, 45, 94%) and total antioxidant capacity (47.13, 47.11, 61%) levels, as compared to lead acetate group. DISCUSSION AND CONCLUSION: These results provide a rationale for an inhibitory role of curcumin and regular exercise in the attenuation of lead-induced neurotoxicity.

Potencial evocado auditivo cortical, análise bioquímica e morfológica em cérebro de ratos submetidos a tratamento subcrônico com chumbo: efeito protetor da suplementação com ferro / Cortical auditory evoked potential, biochemical and morphological analysis in brain of rats treated with subchronic lead: protective effect of supplementation with iron

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...

Potencial evocado auditivo cortical, análise bioquímica e morfológica em cérebro de ratos submetidos a tratamento subcrônico com chumbo: efeito protetor da suplementação com ferro / Cortical Auditory Evoked Potential, biochemical and morphological analysis in brain of rats treated with subchronic lead: protective effect of supplementation with iron

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...

Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure.

Long-term deficits in cognitive function are the principal effects of lead (Pb2+) exposure in children and can be modeled in experimental animals. Current therapeutic approaches in the treatment of childhood Pb2+ intoxication are not effective in reversing learning deficits once they have occurred. We report that environmental enrichment reverses long-term deficits in spatial learning produced by developmental Pb2+ exposure in rats. Enhanced learning performance of Pb2+-exposed animals reared in an enriched environment was associated with recovery of deficits in N-methyl-D-aspartate receptor subunit 1 (NR1) mRNA and induction of brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. The effect of environmental enrichment on NR1 and BDNF gene expression was specific to Pb2+-exposed animals and was present in the absence of changes in the NR2B subunit of the N-methyl-D-aspartate receptor, GluR1, alpha CamKII, or PSD-95 gene expression measured in the same animals. Our findings demonstrate that the learning impairments and NR1 subunit mRNA deficits resulting from developmental Pb2+ exposure are reversible if the animals are provided with an enriched environment even after the exposure has occurred. We propose environmental enrichment as a basis for the treatment of childhood Pb2+ intoxication.