RESUMO
The Funil Reservoir receives a large amount of xenobiotics from the Paraíba do Sul River (PSR) from large number of industries and municipalities in the watershed. This study aimed to assess environmental quality along the longitudinal profile of the Paraíba do Sul River-Funil Reservoir system, by using biomarkers and bioindicators in a selected fish species. The raised hypothesis is that Funil Reservoir acts as a filter for the xenobiotics of the PSR waters, improving river water quality downstream the dam. Two biomarkers, the ethoxyresorufin-O-deethylase activity (EROD), measured as fluorimetricly in S9 hepatic fraction, and the micronuclei frequency (MN), observed in erythrocytes of the cytoplasm, and three bioindicators, the hepatosomatic index (HSI), gonadosomatic index (GSI) and condition factor (CF) were used in Pimelodus maculatus, a fish species widely distributed in the system. Four zones were searched through a longitudinal gradient: 1, river upstream from the reservoir; 2, upper reservoir; 3, lower reservoir; 4, river downstream of the reservoir. EROD activity and HSI and GSI had significant differences among the zones (P<0.05). The upper reservoir had the lowest EROD activity and HSI, whereas the river downstream of the reservoir had the highest EROD and lowest GSI. The river upstream from the reservoir showed the highest HSI and GSI. It is suggested that the lowest environmental condition occur at the river downstream of the reservoir, where it seems to occur more influence of xenobiotics, which could be associated with hydroelectric plant operation. The hypothesis that Funil reservoir acts as a filter decanting pollution from the Paraíba do Sul River waters was rejected. These results are novel information on this subject for a native fish species and could be useful for future comparisons with other environments.(AU)
O reservatório do Funil recebe uma grande quantidade de contaminantes xenobióticos do Rio Paraíba do Sul (RPS) provenientes de grandes indústrias e municípios situados na bacia hidrográfica. O objetivo deste estudo é avaliar a qualidade ambiental ao longo de um perfil longitudinal do sistema rio Paraíba do Sul-reservatório do Funil, através de biomarcadores e bioindicadores em uma espécie de peixe selecionada. A hipótese a ser testada é de que o reservatório do Funil funciona como filtro para poluentes xenobioticos de águas do rio Paraíba do Sul, melhorando a qualidade da água à jusante da represa. Foram usados dois biomarcadores: a atividade de etoxiresorufina-O-desetilase (EROD), medida fluorimetricamente na fração S9 hepática, e a Freqüência de Micronúcleos (MN), observada no citoplasma dos eritrócitos; e também três bioindicadores: índice hepato-somático (IHS), índice gonado-somático (IGS) e Fator de Condição (FC) em Pimelodus maculatus, uma espécie de peixe amplamente distribuída no sistema. Quatro zonas foram amostrados ao longo do gradiente longitudinal: 1, rio a montante do reservatório; 2, parte superior do reservatório; 3, parte inferior do reservatório; 4, rio à jusante do reservatório. A atividade de EROD, o IHS e o IGS apresentaram diferenças significativas (P<0.05) entre as zonas. A atividade EROD e o IHS foram mais baixos na parte superior do reservatório, enquanto que no rio à jusante do reservatório, a atividade de EROD foi mais alta e o IGS foi mais baixo. O rio acima do reservatório apresentou maiores IHS e IGS. É sugerido que a pior condição ambiental ocorreu no rio abaixo do reservatório, o que poderia ser associado às influências das operações da usina hidroelétrica. A hipótese de que o reservatório do Funil atue como filtro decantando a poluição do rio Paraíba do Sul foi rejeitada. Estes dados são novas informações sobre este tema para uma espécie nativa e podem ser úteis para futuras comparações outros ambientes.(AU)
Assuntos
Animais , Peixes-Gato , Biomarcadores , Biomarcadores Ambientais , Monitoramento Ambiental , BrasilRESUMO
Abstract The Funil Reservoir receives a large amount of xenobiotics from the Paraíba do Sul River (PSR) from large number of industries and municipalities in the watershed. This study aimed to assess environmental quality along the longitudinal profile of the Paraíba do Sul River-Funil Reservoir system, by using biomarkers and bioindicators in a selected fish species. The raised hypothesis is that Funil Reservoir acts as a filter for the xenobiotics of the PSR waters, improving river water quality downstream the dam. Two biomarkers, the ethoxyresorufin-O-deethylase activity (EROD), measured as fluorimetricly in S9 hepatic fraction, and the micronuclei frequency (MN), observed in erythrocytes of the cytoplasm, and three bioindicators, the hepatosomatic index (HSI), gonadosomatic index (GSI) and condition factor (CF) were used in Pimelodus maculatus, a fish species widely distributed in the system. Four zones were searched through a longitudinal gradient: 1, river upstream from the reservoir; 2, upper reservoir; 3, lower reservoir; 4, river downstream of the reservoir. EROD activity and HSI and GSI had significant differences among the zones (P<0.05). The upper reservoir had the lowest EROD activity and HSI, whereas the river downstream of the reservoir had the highest EROD and lowest GSI. The river upstream from the reservoir showed the highest HSI and GSI. It is suggested that the lowest environmental condition occur at the river downstream of the reservoir, where it seems to occur more influence of xenobiotics, which could be associated with hydroelectric plant operation. The hypothesis that Funil reservoir acts as a filter decanting pollution from the Paraíba do Sul River waters was rejected. These results are novel information on this subject for a native fish species and could be useful for future comparisons with other environments.
Resumo O reservatório do Funil recebe uma grande quantidade de contaminantes xenobióticos do Rio Paraíba do Sul (RPS) provenientes de grandes indústrias e municípios situados na bacia hidrográfica. O objetivo deste estudo é avaliar a qualidade ambiental ao longo de um perfil longitudinal do sistema rio Paraíba do Sul-reservatório do Funil, através de biomarcadores e bioindicadores em uma espécie de peixe selecionada. A hipótese a ser testada é de que o reservatório do Funil funciona como filtro para poluentes xenobioticos de águas do rio Paraíba do Sul, melhorando a qualidade da água à jusante da represa. Foram usados dois biomarcadores: a atividade de etoxiresorufina-O-desetilase (EROD), medida fluorimetricamente na fração S9 hepática, e a Freqüência de Micronúcleos (MN), observada no citoplasma dos eritrócitos; e também três bioindicadores: Índice hepato-somático (IHS), Índice gonado-somático (IGS) e Fator de Condição (FC) em Pimelodus maculatus, uma espécie de peixe amplamente distribuída no sistema. Quatro zonas foram amostrados ao longo do gradiente longitudinal: 1, rio a montante do reservatório; 2, parte superior do reservatório; 3, parte inferior do reservatório; 4, rio à jusante do reservatório. A atividade de EROD, o IHS e o IGS apresentaram diferenças significativas (P<0.05) entre as zonas. A atividade EROD e o IHS foram mais baixos na parte superior do reservatório, enquanto que no rio à jusante do reservatório, a atividade de EROD foi mais alta e o IGS foi mais baixo. O rio acima do reservatório apresentou maiores IHS e IGS. É sugerido que a pior condição ambiental ocorreu no rio abaixo do reservatório, o que poderia ser associado às influências das operações da usina hidroelétrica. A hipótese de que o reservatório do Funil atue como filtro decantando a poluição do rio Paraíba do Sul foi rejeitada. Estes dados são novas informações sobre este tema para uma espécie nativa e podem ser úteis para futuras comparações outros ambientes.
Assuntos
Animais , Peixes-Gato/fisiologia , Peixes-Gato/genética , Biomarcadores/análise , Biomarcadores/metabolismo , Monitoramento Ambiental/métodos , Brasil , RiosRESUMO
The Funil Reservoir receives a large amount of xenobiotics from the Paraíba do Sul River (PSR) from large number of industries and municipalities in the watershed. This study aimed to assess environmental quality along the longitudinal profile of the Paraíba do Sul River-Funil Reservoir system, by using biomarkers and bioindicators in a selected fish species. The raised hypothesis is that Funil Reservoir acts as a filter for the xenobiotics of the PSR waters, improving river water quality downstream the dam. Two biomarkers, the ethoxyresorufin-O-deethylase activity (EROD), measured as fluorimetricly in S9 hepatic fraction, and the micronuclei frequency (MN), observed in erythrocytes of the cytoplasm, and three bioindicators, the hepatosomatic index (HSI), gonadosomatic index (GSI) and condition factor (CF) were used in Pimelodus maculatus, a fish species widely distributed in the system. Four zones were searched through a longitudinal gradient: 1, river upstream from the reservoir; 2, upper reservoir; 3, lower reservoir; 4, river downstream of the reservoir. EROD activity and HSI and GSI had significant differences among the zones (P<0.05). The upper reservoir had the lowest EROD activity and HSI, whereas the river downstream of the reservoir had the highest EROD and lowest GSI. The river upstream from the reservoir showed the highest HSI and GSI. It is suggested that the lowest environmental condition occur at the river downstream of the reservoir, where it seems to occur more influence of xenobiotics, which could be associated with hydroelectric plant operation. The hypothesis that Funil reservoir acts as a filter decanting pollution from the Paraíba do Sul River waters was rejected. These results are novel information on this subject for a native fish species and could be useful for future comparisons with other environments.
Assuntos
Biomarcadores , Peixes-Gato , Monitoramento Ambiental/métodos , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Brasil , Peixes-Gato/genética , Peixes-Gato/fisiologia , RiosRESUMO
The crude latex of "Crown-of-Thorns" (Euphorbia milii var hislopii, syn E.splendens) is a potent plant molluscicide. For this reason, toxicological studies have been performed to evaluate the health risks posed by its use in schistosomiasis control programs. The present study is part of a more comprehensive immunotoxicological evaluation of this molluscicide. Here, we investigated the effects of E. milii latex on the proliferation of human lymphocytes in vitro. Lyophilized latex of E. milii (0, 0.5, 5, 25 and 50 µg/ml) was incubated with whole blood in the presence of proliferation stimulators, i.e. lectins (phytohemagglutinin, concanavalin A and pokeweed mitogen), as well as with human monoclonal antibody against CD3 and tetanus toxoid. Cell proliferation was measured by ³H-thymidine incorporation, and the effects of latex on mitogen-induced cell proliferation were compared to the effects of 10 ng/ml of 12-O-tetradecanoylphorbol-13-acetate (TPA). Results showed that mitogen-induced cell proliferation was markedly enhanced by E. milii latex. This synergistic effect of latex on mitogen-induced lymphocyte proliferation may be due to the presence of TPA-like phorbol esters and/or to mitogenic plant lectins.
O látexbrutoda "Coroa de Cristo" (Euphorbia miliivarhislopii, syn E.splendens) é um potente moluscicidavegetal. Neste sentido, são necessários estudos toxicológicosque visemavaliar possíveis riscos à saúdeassociados ao uso em larga escala desta espécie em áreas endêmicas para esquistossomose. O presente estudo é parte deuma avaliação mais abrangentesobre o potencial tóxico destemoluscicida. Foram investigados in vitro osefeitos dolátex da E.miliisobre a proliferação delinfócitoshumanos. O látexliofilizado (0; 0,5;5;25 e 50 µg/ml)foi incubado comsangue totalna presençade agentes mitogênicos, tais como lectinas(fitohemaglutinina, concanavalina Ae pokeweed), anticorpomonoclonalhumano anti-CD3etoxóide tetânico. A proliferação celularfoi quantificada atravésincorporaçãode ³H-timidina eos efeitos do látexnaproliferação celular induzida por agentes mitogênicosforam comparados comos efeitos de10 ng/mlde12-O-tetradecanoilforbol-13-acetato (TPA). Os resultados demonstram quea proliferação celular induzida poragentes mitogênicosfoimarcadamenteaumentada na presença do látex daE.milii.Oefeito sinérgico observado pode ser devidoà presença deésteres de forbol, como o TPA, e/oude lectinas com ação mitogênica presentes nesta espécie vegetal.
Assuntos
Humanos , Masculino , Feminino , Euphorbia/metabolismo , Látex/análise , Plantas Medicinais/classificação , Ésteres de Forbol/classificação , Linfócitos/metabolismoRESUMO
This study compared the efficacies of two N-methylglucomine antimoniate (MA) dose regimens for treating macaques with Leishmania braziliensis-induced chronic skin disease. Whereas all animals treated with the full dose (20 mg MA/kg/day) were cured, 50% of the monkeys receiving a low-dose regimen (5 mg MA/kg/day) relapsed. The antimony concentrations in macaque plasma and tissue samples were greater in the full-dose group than in that receiving a subtherapeutic MA regimen. Our data also suggest the presence of drug-induced hepatic pathology.
Assuntos
Antiprotozoários/uso terapêutico , Leishmaniose Cutânea/tratamento farmacológico , Meglumina/uso terapêutico , Compostos Organometálicos/uso terapêutico , Animais , Antimônio/sangue , Antiprotozoários/administração & dosagem , Rim/parasitologia , Rim/patologia , Leishmania braziliensis , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/patologia , Fígado/parasitologia , Fígado/patologia , Macaca mulatta , Meglumina/administração & dosagem , Antimoniato de Meglumina , Compostos Organometálicos/administração & dosagem , Baço/parasitologia , Baço/patologiaRESUMO
We investigated the presence and inducibility of CYP1A in suckermouth catfish (Hypostomus affinis and Hypostomus auroguttatus, Loricariidae), tilapia (Oreochromis niloticus, Cichlidae) and mice (Mus musculus, Muridae). Alkoxyresorufin-O-dealkylases (EROD, MROD, PROD and BROD) were detected and proved to be inducible (beta-naphthoflavone, BNF or dimethylbenz[a]anthracene, DMBA, 50 mg/kg bw ip) in liver microsomes from tilapia and mice. In loricariids, alkoxyresorufin-O-dealkylases were either undetectable (MROD/EROD) or very low (PROD/BROD), and so they remained after treatment with BNF or DMBA. Ethoxycoumarin-O-deethylase (ECOD) was recorded in all species and proved not to be inducible by BNF or DMBA. In loricariids and tilapia, ECOD was not depressed by a concentration of alpha-naphthoflavone (CYP1A-inhibitor) that markedly depressed EROD in tilapia. A CYP1A-like protein was detected by a monoclonal antibody in rats, mice and tilapia, but not in loricariids. A polyclonal antibody, however, detected a CYP1A-like protein in liver microsomes of loricariids. Suckermouth catfish, rats, mice and tilapia express a protein reactive with a polyclonal antibody against trout CYP3A. Loricariids and tilapia exhibited marked genotoxic responses (enhanced incidence of micronucleated erythrocytes) following treatment DMBA (50 mg/kg bw ip), a promutagen activated by CYP1A/1B. Therefore, although not exhibiting EROD, a CYP1A-mediated activity, loricariids converted DMBA into its genotoxic metabolites. Our findings suggest that the CYP1A-like protein of locariid catfish recognizes DMBA, but not ethoxyresorufin, as a substrate.
Assuntos
Hidrocarboneto de Aril Hidroxilases/metabolismo , Peixes-Gato/metabolismo , Proteínas de Peixes/metabolismo , Fígado/enzimologia , Tilápia/metabolismo , O-Dealquilase 7-Alcoxicumarina/metabolismo , 9,10-Dimetil-1,2-benzantraceno/metabolismo , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Hidrocarboneto de Aril Hidroxilases/antagonistas & inibidores , Hidrocarboneto de Aril Hidroxilases/biossíntese , Benzoflavonas/farmacologia , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP2B1/metabolismo , Citocromo P-450 CYP3A/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Indução Enzimática , Inibidores Enzimáticos/farmacologia , Proteínas de Peixes/biossíntese , Cinética , Fígado/efeitos dos fármacos , Camundongos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Microssomos Hepáticos/enzimologia , Mutagênicos/metabolismo , Mutagênicos/toxicidade , Oxazinas/metabolismo , Receptores de Hidrocarboneto Arílico/agonistas , Especificidade por Substrato , beta-Naftoflavona/farmacologiaRESUMO
The effects of schistosomiasis on microsomal enzymes were studied on post-infection day 90 when accumulated damage and fibrosis are most intense but granulomatous reaction around the eggs harbored in the liver is smaller than during the earlier phases. Swiss Webster (SW) and DBA/2 mice of either sex (N = 12 per sex per group) were infected with 100 Schistosoma mansoni cercariae on postnatal day 10 and killed on post-infection day 90. Cytochrome P-450 (CYP) concentration and alkoxyresorufin-O-dealkylases (EROD, MROD, BROD, and PROD), p-nitrophenol-hydroxylase (PNPH), coumarin-7-hydroxylase (COH), and UDP-glucuronosyltransferase (UGT) activities were measured in hepatic microsomes. Age-matched mice of the same sex and strain were used as controls. In S. mansoni-infected mice, CYP1A- and 2B-mediated activities (control = 100 percent) were reduced in SW (EROD: male (M) 36 percent, female (F) 38 percent; MROD: M 38 percent, F 39 percent; BROD: M 46 percent, F 19 percent; PROD: M 50 percent, F 28 percent) and DBA/2 mice (EROD: M 64 percent, F 58 percent; MROD: M 60 percent; BROD: F 49 percent; PROD: M 73 percent) while PNPH (CYP2E1) was decreased in SW (M 31 percent, F 38 percent) but not in DBA/2 mice. COH did not differ between infected and control DBA/2 and UGT, a phase-2 enzyme, was not altered by infection. In conclusion, chronic S. mansoni infection reduced total CYP content and all CYP-mediated activities evaluated in SW mice, including those catalyzed by CYP2E1 (PNPH), CYP1A (EROD, MROD) and 2B (BROD, PROD). In DBA/2 mice, however, CYP2A5- and 2E1-mediated activities remained unchanged while total CYP content and activities mediated by other CYP isoforms were depressed during chronic schistosomiasis.
Assuntos
Animais , Feminino , Masculino , Camundongos , /metabolismo , Hepatopatias Parasitárias/enzimologia , Microssomos Hepáticos/enzimologia , Esquistossomose mansoni/enzimologia , Doença Crônica , Camundongos Endogâmicos DBA , Microssomos Hepáticos/parasitologia , Fatores de TempoRESUMO
The effects of schistosomiasis on microsomal enzymes were studied on post-infection day 90 when accumulated damage and fibrosis are most intense but granulomatous reaction around the eggs harbored in the liver is smaller than during the earlier phases. Swiss Webster (SW) and DBA/2 mice of either sex (N = 12 per sex per group) were infected with 100 Schistosoma mansoni cercariae on postnatal day 10 and killed on post-infection day 90. Cytochrome P-450 (CYP) concentration and alkoxyresorufin-O-dealkylases (EROD, MROD, BROD, and PROD), p-nitrophenol-hydroxylase (PNPH), coumarin-7-hydroxylase (COH), and UDP-glucuronosyltransferase (UGT) activities were measured in hepatic microsomes. Age-matched mice of the same sex and strain were used as controls. In S. mansoni-infected mice, CYP1A- and 2B-mediated activities (control = 100%) were reduced in SW (EROD: male (M) 36%, female (F) 38%; MROD: M 38%, F 39%; BROD: M 46%, F 19%; PROD: M 50%, F 28%) and DBA/2 mice (EROD: M 64%, F 58%; MROD: M 60%; BROD: F 49%; PROD: M 73%) while PNPH (CYP2E1) was decreased in SW (M 31%, F 38%) but not in DBA/2 mice. COH did not differ between infected and control DBA/2 and UGT, a phase-2 enzyme, was not altered by infection. In conclusion, chronic S. mansoni infection reduced total CYP content and all CYP-mediated activities evaluated in SW mice, including those catalyzed by CYP2E1 (PNPH), CYP1A (EROD, MROD) and 2B (BROD, PROD). In DBA/2 mice, however, CYP2A5- and 2E1-mediated activities remained unchanged while total CYP content and activities mediated by other CYP isoforms were depressed during chronic schistosomiasis.
Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Hepatopatias Parasitárias/enzimologia , Microssomos Hepáticos/enzimologia , Esquistossomose mansoni/enzimologia , Animais , Doença Crônica , Feminino , Masculino , Camundongos , Camundongos Endogâmicos DBA , Microssomos Hepáticos/parasitologia , Fatores de TempoRESUMO
We investigated the relationship between fetal body weight at term (pregnancy day 21) and the extent of ossification of sternum, metacarpus, metatarsus, phalanges (proximal, medial and distal) of fore- and hindlimbs and cervical and coccygeal vertebrae in Wistar rats. The relationships between fetal body weight and sex, intrauterine position, uterine horn, horn size, and litter size were determined using historical control data (7594 fetuses; 769 litters) of untreated rats. Relationships between body weight and degree of ossification were examined in a subset of 1484 historical control fetuses (154 litters) which were subsequently cleared and stained with alizarin red S. Fetal weight was independent of horn size, uterine horn side (left or right) or intrauterine position. Males were heavier than females and fetal weight decreased with increasing litter size. Evaluation of the skeleton showed that ossification of sternum, metacarpus and metatarsus was extensively complete and independent of fetal weight on pregnancy day 21. In contrast, the extent of ossification of fore- and hindlimb phalanges and of cervical and sacrococcygeal vertebrae was dependent on fetal body weight. The strongest correlation between body weight and degree of ossification was found for hindlimb, medial and proximal phalanges. Our data therefore suggest that, in full-term rat fetuses (day 21), reduced ossification of sternum, metacarpus and metatarsus results from a localized impairment of bone calcification (i.e., a malformation or variation) rather than from general growth retardation and that ossification of hindlimb (medial and proximal) phalanges is a good indicator of treatment-induced fetal growth retardation.
Assuntos
Desenvolvimento Fetal/fisiologia , Peso Fetal , Osteogênese/fisiologia , Animais , Feminino , Retardo do Crescimento Fetal/diagnóstico , Idade Gestacional , Tamanho da Ninhada de Vivíparos , Masculino , Gravidez , Ratos , Ratos WistarRESUMO
We investigated the relationship between fetal body weight at term (pregnancy day 21) and the extent of ossification of sternum, metacarpus, metatarsus, phalanges (proximal, medial and distal) of fore- and hindlimbs and cervical and coccygeal vertebrae in Wistar rats. The relationships between fetal body weight and sex, intrauterine position, uterine horn, horn size, and litter size were determined using historical control data (7594 fetuses; 769 litters) of untreated rats. Relationships between body weight and degree of ossification were examined in a subset of 1484 historical control fetuses (154 litters) which were subsequently cleared and stained with alizarin red S. Fetal weight was independent of horn size, uterine horn side (left or right) or intrauterine position. Males were heavier than females and fetal weight decreased with increasing litter size. Evaluation of the skeleton showed that ossification of sternum, metacarpus and metatarsus was extensively complete and independent of fetal weight on pregnancy day 21. In contrast, the extent of ossification of fore- and hindlimb phalanges and of cervical and sacrococcygeal vertebrae was dependent on fetal body weight. The strongest correlation between body weight and degree of ossification was found for hindlimb, medial and proximal phalanges. Our data therefore suggest that, in full-term rat fetuses (day 21), reduced ossification of sternum, metacarpus and metatarsus results from a localized impairment of bone calcification (i.e., a malformation or variation) rather than from general growth retardation and that ossification of hindlimb (medial and proximal) phalanges is a good indicator of treatment-induced fetal growth retardation.