RESUMO
Lead (Pb) is a toxic metal that is widely used by metallurgical industries such as car battery recycling. Exposure to the metal may modify the redox status of the cells and consequently result in changes in activities of important enzymes such as delta-aminolevulinic acid dehydratase (ALAD) and glutathione peroxidase (GPx). Similarly, genetic polymorphisms may modulate the activities of enzymes related to detoxification processes of the metal and may modify Pb body burden. Therefore, the aims of the present study were (i) to evaluate the correlation between blood lead levels (BLL) and activities of the enzymes ALAD and GPx, and (ii) to determine whether activities of these enzymes may be influenced by polymorphisms in ALAD and GPx genes in Brazilian automotive battery workers chronically exposed to Pb, as well as the effects of these polymorphisms on BLL. Our study included 257 participants; BLL were determined by inductively couple plasma-mass spectrometry (ICP-MS), and the activities of the enzymes ALAD and GPx were quantified spectrophotometrically; and genotyping of ALAD (rs1800435) and GPx-1 (rs1800668) polymorphisms was performed by TaqMan assays (real-time polymerase chain reaction, RT-PCR). Significant negative correlations were found between BLL and ALAD activity. Subjects who carried at least one polymorphic allele for ALAD gene displayed markedly lower ALAD activities, while no significant effect was observed regarding GPx-1 polymorphism and activity of the same enzyme. Further, ALAD and GPx-1 polymorphisms exerted no marked influence on BLL. Taken together, our results showed that BLL affected ALAD but not GPx activities, and these were not modulated by polymorphisms in ALAD and GPx gene. Further, the rs1800435 SNP showed a tendency to modulate ALAD activity, while the rs1800668 SNP did not modulate GPx activity in Brazilian automotive battery workers exposed to Pb.
Assuntos
Glutationa Peroxidase/genética , Chumbo/toxicidade , Metalurgia , Exposição Ocupacional , Sintase do Porfobilinogênio/genética , Adolescente , Adulto , Idoso , Automóveis , Brasil , Estudos Transversais , Glutationa Peroxidase/sangue , Humanos , Chumbo/sangue , Espectrometria de Massas , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Sintase do Porfobilinogênio/sangue , Reação em Cadeia da Polimerase em Tempo Real , Reciclagem , Adulto Jovem , Glutationa Peroxidase GPX1RESUMO
Over the last decades, the presence of methylmercury (MeHg) in the Amazon region of Brazil and its adverse human health effects have given rise to much concern. The biotransformation of MeHg occurs mainly through glutathione (GSH) in the bile mediated by conjugation with glutathione S-transferases (GST). Epidemiological evidence has shown that genetic polymorphisms may affect the metabolism of MeHg. The aim of this study was to evaluate the association between GST polymorphisms, GSH, and Hg levels in blood (B-Hg) and in hair (H-Hg) of an Amazon population chronically exposed to the metal through fish consumption. Blood and hair samples were collected from 144 volunteers (71 men, 73 women). B-Hg and H-Hg levels were determined by inductively coupled plasma-mass spectrometry, and GSH levels were evaluated by a spectrophotometric method. GSTM1 and T1 genotyping evaluation were carried out by multiplex polymerase chain reaction (PCR). Mean levels of B-Hg and H-Hg were 37.7 ± 24.5 µg/L and 10.4 ± 7.4 µg/g, respectively; GSH concentrations ranged from 0.52 to 2.89 µM/ml of total blood. Distributions for GSTM1/T1, GSTM1/GSTT1*0, GSTM1*0/T1, and GSTM1*0/GSTT1*0 genotypes were 35.4, 22.2, 25.0, and 17.4%, respectively. GSTT1 genotype carriers presented lower levels of B-Hg and H-Hg when compared to other genotypes carriers. In addition, GSTM1*0/GSTT1*0 individuals presented higher Hg levels in blood and hair than subjects presenting any other genotypes. There appeared to be no evidence of an effect of polymorphisms on GSH levels. Therefore, our data suggest that GST polymorphisms may be associated with MeHg detoxification.
Assuntos
Glutationa Transferase/metabolismo , Compostos de Metilmercúrio/metabolismo , Poluentes Químicos da Água/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , DNA/genética , Feminino , Contaminação de Alimentos , Glutationa Transferase/sangue , Glutationa Transferase/genética , Cabelo/química , Humanos , Masculino , Compostos de Metilmercúrio/sangue , Compostos de Metilmercúrio/química , Pessoa de Meia-Idade , Polimorfismo Genético , Poluentes Químicos da Água/química , Adulto JovemRESUMO
The Miconia genus, a plant widely used for medicine, occurs in tropical America and its extracts and isolated compounds have demonstrated antibiotic, antitumoral, analgesic and antimalarial activities. However, no study concerning its genotoxicity has been conducted and it is necessary to determine its potential mutagenic effects to develop products and chemicals from these extracts. This study assessed the cytotoxicity, mutagenicity and the protective effects of methanolic extracts from Miconia species on Chinese hamster lung fibroblast cell cultures (V79). The cytotoxicity was evaluated using a clonogenic assay. Cultures exposed to the extract of Miconia albicans up to a concentration of 30 µg/mL, M. cabucu up to 40 µg/mL, M. albicans up to 40 µg/mL and M. stenostachya up to 60 µg/mL exhibited a cytotoxic effect on the cells. The clonogenic assay used three non-cytotoxic concentrations (5, 10 and 20 µg/mL) to evaluate mutagenicity and antimutagenicity of the extracts. Cultures were treated with these three extract concentrations (mutagenicity test) or the extract associated with doxorubicin (DXR) (antimutagenicity test) in three protocols (pre-, simultaneous and post-treatments). Distilled water and DXR were used as negative and positive controls, respectively. In the micronucleus (MN) test, a significant reduction was observed in MN frequency in cultures treated with DXR and extracts compared to those receiving only DXR; a significant reduction was also observed for the presence of mutagenicity in all treatments. This study confirmed the safe use of Miconia extracts at the concentrations tested and reinforced the therapeutic properties previously described for Miconia species by showing their protective effects on doxorubicin-induced mutagenicity.
Assuntos
Antimutagênicos/farmacologia , Dano ao DNA/efeitos dos fármacos , Doxorrubicina/toxicidade , Melastomataceae/química , Mutagênicos/toxicidade , Extratos Vegetais , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Testes para Micronúcleos , Componentes Aéreos da Planta/química , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidadeRESUMO
Propolis has been used in folk medicine since ancient times and is known for its antimicrobial, antiparasitic, antiviral, anti-inflammatory, antitumoral and antioxidant properties. In view of the great therapeutic interest in propolis and the small number of studies regarding its mechanism of action, the aim of the present study was to evaluate the mutagenic and antimutagenic effects of propolis using Chinese hamster ovary cells. Parameters such as the frequency of chromosome aberrations and mitotic index were analyzed. The results showed that, on one hand, the highest propolis tested concentration displayed a small but significant increase in the frequency of chromosome aberrations, and on the other hand, it was observed that the lowest tested concentration significantly reduced the chromosome damage induced by the chemotherapeutic agent doxorubicin. The present results indicate that propolis shows the characteristic of a "Janus" compound, i.e., propolis is genotoxic at higher concentrations, while at lower concentrations it display a chemopreventive effect on doxorubicin-induced mutagenicity. Flavonoids may be the components of propolis responsible for its both mutagenic and antimutagenic effects, once these compounds may act either as pro-oxidant or as free radicals scavenger, depending on its concentration.