RESUMO
Este estudo investigou a toxicidade pré-natal do inseticida piriproxifeno em ratos Wistar, de forma a detectar possíveis alterações no desenvolvimento fetal da progênie exposta durante o período organogênico. Três doses de piriproxifeno (100, 300 e 500mg.kg-1) foram administradas por via oral às progenitoras, do sexto ao 15º dia de gestação. Os fetos foram submetidos à técnica de diafanização modificada descrita por Taylor e Van Dyke, para avaliação de malformações e alterações esqueléticas. Os resultados não demonstraram a ocorrência de toxicidade materna sistêmica ou alterações nos índices reprodutivos avaliados. Malformações ou alterações teratogênicas não foram detectadas, no entanto alterações esqueléticas sugestivas de retardo no desenvolvimento foram observadas especialmente nas doses mais altas testadas (300mg.kg-1 e 500mg.kg-1). Considerando-se a situação complexa de risco para a saúde humana, mostra-se importante a execução de investigações adicionais, de modo a contribuir para a adequada avaliação de risco do piriproxifeno em água potável.(AU)
This study investigated the prenatal toxicity of the insecticide pyriproxyfen in Wistar rats to detect the possible changes in the fetal development of the progeny exposed during the organogenic period. Three doses of pyriproxyfen (100, 300, and 500mg.kg-1) were administered orally to the progenitors, from day 6 to 15 of gestation. The fetuses were processed using the Taylor and Van Dyke modified diaphanization technique to evaluate malformations and skeletal changes. The results did not demonstrate the occurrence of systemic maternal toxicity or changes in the reproductive indexes evaluated. Malformations or teratogenic changes were not detected, however, skeletal changes suggestive of developmental delay were observed, especially in the highest doses tested (300 mg.kg-1 and 500 mg.kg-1). Owing to the potentially complex situation regarding its risk to human health, it is important that further studies be performed to contribute to the risk assessment of the addition of pyriproxyfen in drinking water.(AU)
Assuntos
Animais , Ratos , Praguicidas/efeitos adversos , Piridinas , Teratogênicos/análise , Desenvolvimento Fetal/efeitos dos fármacos , Ratos Wistar/embriologia , Zika virus , Microcefalia/veterináriaRESUMO
Este estudo investigou a toxicidade pré-natal do inseticida piriproxifeno em ratos Wistar, de forma a detectar possíveis alterações no desenvolvimento fetal da progênie exposta durante o período organogênico. Três doses de piriproxifeno (100, 300 e 500mg.kg-1) foram administradas por via oral às progenitoras, do sexto ao 15º dia de gestação. Os fetos foram submetidos à técnica de diafanização modificada descrita por Taylor e Van Dyke, para avaliação de malformações e alterações esqueléticas. Os resultados não demonstraram a ocorrência de toxicidade materna sistêmica ou alterações nos índices reprodutivos avaliados. Malformações ou alterações teratogênicas não foram detectadas, no entanto alterações esqueléticas sugestivas de retardo no desenvolvimento foram observadas especialmente nas doses mais altas testadas (300mg.kg-1 e 500mg.kg-1). Considerando-se a situação complexa de risco para a saúde humana, mostra-se importante a execução de investigações adicionais, de modo a contribuir para a adequada avaliação de risco do piriproxifeno em água potável.(AU)
This study investigated the prenatal toxicity of the insecticide pyriproxyfen in Wistar rats to detect the possible changes in the fetal development of the progeny exposed during the organogenic period. Three doses of pyriproxyfen (100, 300, and 500mg.kg-1) were administered orally to the progenitors, from day 6 to 15 of gestation. The fetuses were processed using the Taylor and Van Dyke modified diaphanization technique to evaluate malformations and skeletal changes. The results did not demonstrate the occurrence of systemic maternal toxicity or changes in the reproductive indexes evaluated. Malformations or teratogenic changes were not detected, however, skeletal changes suggestive of developmental delay were observed, especially in the highest doses tested (300 mg.kg-1 and 500 mg.kg-1). Owing to the potentially complex situation regarding its risk to human health, it is important that further studies be performed to contribute to the risk assessment of the addition of pyriproxyfen in drinking water.(AU)
Assuntos
Animais , Ratos , Praguicidas/efeitos adversos , Piridinas , Teratogênicos/análise , Desenvolvimento Fetal/efeitos dos fármacos , Ratos Wistar/embriologia , Zika virus , Microcefalia/veterináriaRESUMO
The teratogenic mechanisms triggered by ZIKV are still obscure due to the lack of a suitable animal model. Here we present a mouse model of developmental disruption induced by ZIKV hematogenic infection. The model utilizes immunocompetent animals from wild-type FVB/NJ and C57BL/6J strains, providing a better analogy to the human condition than approaches involving immunodeficient, genetically modified animals, or direct ZIKV injection into the brain. When injected via the jugular vein into the blood of pregnant females harboring conceptuses from early gastrulation to organogenesis stages, akin to the human second and fifth week of pregnancy, ZIKV infects maternal tissues, placentas and embryos/fetuses. Early exposure to ZIKV at developmental day 5 (second week in humans) produced complex manifestations of anterior and posterior dysraphia and hydrocephalus, as well as severe malformations and delayed development in 10.5 days post-coitum (dpc) embryos. Exposure to the virus at 7.5-9.5 dpc induces intra-amniotic hemorrhage, widespread edema, and vascular rarefaction, often prominent in the cephalic region. At these stages, most affected embryos/fetuses displayed gross malformations and/or intrauterine growth restriction (IUGR), rather than isolated microcephaly. Disrupted conceptuses failed to achieve normal developmental landmarks and died in utero. Importantly, this is the only model so far to display dysraphia and hydrocephalus, the harbinger of microcephaly in humans, as well as arthrogryposis, a set of abnormal joint postures observed in the human setting. Late exposure to ZIKV at 12.5 dpc failed to produce noticeable malformations. We have thus characterized a developmental window of opportunity for ZIKV-induced teratogenesis encompassing early gastrulation, neurulation and early organogenesis stages. This should not, however, be interpreted as evidence for any safe developmental windows for ZIKV exposure. Late developmental abnormalities correlated with damage to the placenta, particularly to the labyrinthine layer, suggesting that circulatory changes are integral to the altered phenotypes.
Assuntos
Artrogripose/virologia , Modelos Animais de Doenças , Hidrocefalia/virologia , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/virologia , Zika virus/fisiologia , Animais , Artrogripose/embriologia , Artrogripose/imunologia , Artrogripose/patologia , Feminino , Humanos , Hidrocefalia/embriologia , Hidrocefalia/imunologia , Hidrocefalia/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Placenta/anormalidades , Placenta/imunologia , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/patologia , Teratogênicos/análise , Infecção por Zika virus/embriologia , Infecção por Zika virus/imunologia , Infecção por Zika virus/patologiaRESUMO
The biosafety of innovative procedures that utilize stem cells in regenerative medicine has been addressed in several studies. Previous work has showed no tumour formation following the use of feline and human amniotic membrane-derived stem cells (AMSCs). In contrast, tumour formation was observed when canine AMSCs were utilized. These findings suggested that feline and human, but not canine, AMSCs are suitable for cell transplantation trials. This study aimed to further evaluate the feasibility of utilizing canine AMSCs for transplantation purposes as well as for felines. We tested teratoma formation following cell injection into BALB/c nude mice and then assessed expression of haematopoietic, mesenchymal, tumorigenic, pluripotency and cellular regulation markers using flow cytometry and qPCR. The use of canine AMSCs did not result in macroscopic tumour formation as determined 60 days after transplantation. The immunophenotypic characterization by flow cytometry revealed expression of mesenchymal markers (CD73 and CD90) and expression of the pluripotent marker OCT4 and SOX2. Quantitative PCR analysis revealed that there were no differences in the patterns of gene expression (CD34, CD73, OCT4, CD30 and P53) between canine and feline AMSCs, with the exception of the expression of SOX2 and CD90.
Assuntos
Âmnio/citologia , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Teratogênicos/análise , Teratoma/patologia , Animais , Biomarcadores , Gatos , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Cães , Citometria de Fluxo , Expressão Gênica , Células-Tronco Mesenquimais/patologia , Camundongos , Camundongos NusRESUMO
El etanol y el isopropanol son, de los alcoholes alifáticos de cadena corta, los más frecuentemente asociados a la actividad humana tanto a nivel industrial como en el entorno doméstico. En este trabajo se presentan los principales hallazgos reportados en la literatura para ensayos de genotoxicidad y teratogénesis en modelos experimentales de distinto nivel de complejidad, con especial énfasis en Drosophila melanogaster. El metabolismo de estos alcoholes es semejante en Drosophila y en humanos por lo cual la mosca es un buen modelo in vivo para la evaluación de sus potenciales efectos tóxicos, genotóxicos y teratogénicos.
Ethanol and isopropanol are two of the short chain aliphatic alcohols more frequently associated to the human environment, both in the industrial and domestic conditions. The aim of this work was to present the main findings reported in the literature about their genotoxicity and teratogenicity in experimental models of different level of complexity, with special emphasis in Drosophila melanogaster. Taking into account that the metabolism of both alcohols in Drosophila and humans is similar, the fly is a good model for the evaluation of their potentially toxic, genotoxic and teratogenic effects.
Assuntos
Animais , 2-Propanol/metabolismo , 2-Propanol/toxicidade , Etanol/metabolismo , Etanol/toxicidade , Drosophila melanogaster/efeitos dos fármacos , Genotoxicidade/análise , Teratogênicos/análise , Toxicogenética/métodosRESUMO
A high-performance liquid chromatography-fluorescence (HPLC-FD) method for aflatoxin quantification in brazil nuts was developed. Samples of brazil nuts collected in Brazilian markets were extracted with methanol:water and cleaned using an immunoaffinity column. Aflatoxins were eluted with methanol and a post-column derivatisation was performed with bromine, using a Kobra Cell system. The optimised method for total aflatoxins was sensitive, with detection and quantification limits of 0.05 and 0.25 µg kg⻹, respectively. The method was accurate, with recovery values of 87.6%; 85.3% and 85.0% for 0.5, 5.0 and 14.6 µg kg⻹ spiked levels, respectively. It was shown that the method was applicable to brazil nuts. From a total of 95 brazil nut samples analysed from 21 São Paulo supermarket samples and 51 Manaus and 23 Belém street markets samples, 37.9% showed detectable levels of aflatoxins and three exceeded the recommended Codex Alimentarius limit of 10 µg kg⻹ for ready-to-eat brazil nuts.
Assuntos
Aflatoxinas/análise , Bertholletia/química , Fast Foods/análise , Contaminação de Alimentos , Inspeção de Alimentos/métodos , Nozes/química , Venenos/análise , Métodos Analíticos de Preparação de Amostras , Brasil , Carcinógenos/análise , Cromatografia de Afinidade , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , União Europeia , Fast Foods/economia , Fast Foods/normas , Manipulação de Alimentos , Fidelidade a Diretrizes , Limite de Detecção , Nozes/economia , Nozes/normas , Reprodutibilidade dos Testes , Espectrometria de Fluorescência , Teratogênicos/análiseRESUMO
The occurrence of ochratoxin A (OTA) in wine from 2002 to 2008 harvest, traded in Rio de Janeiro State, was evaluated by analysing 43 national and 37 imported wines from Argentina (32) and Chile (5), adding up to 80 samples in total. OTA determination was performed using immunoaffinity columns and high-performance liquid chromatography. In 80 wine samples analysed, 25 (31.3%) were positive, presenting levels greater than 0.020 ng OTA mL⻹. It was not detected in imported wines. Within national wines, 58.1% of the samples were contaminated, with levels ranging from 0.020 to 0.050 ng mL⻹. The toxin was detected in 18 (69.2%) of 26 samples analysed of red table wine. Wines from 2008 harvest presented 84.6% of samples contaminated in 13 samples analysed. Despite the levels found in this study, they are below Brazilian tolerance limits. Nevertheless, the presence of OTA as found contributes to the human exposure to this toxin.
Assuntos
Contaminação de Alimentos , Ocratoxinas/análise , Teratogênicos/análise , Vinho/análise , Brasil , Cromatografia de Afinidade , Cromatografia Líquida de Alta Pressão , Dieta/etnologia , Inspeção de Alimentos , Humanos , Imunossupressores/análise , Limite de Detecção , Reprodutibilidade dos Testes , Análise Espaço-Temporal , Espectrometria de Fluorescência , Vinho/economiaRESUMO
Although it is a frequent accident in a few countries, scorpion envenomation during pregnancy remains scarcely studied. In the present study, the effects of repetitive maternal exposure to Buthus occitanus tunetanus venom are investigated and its possible embryotoxic consequences on rats. Primigravid rats received a daily intraperitoneal dose of 1 mL/kg of saline solution or 300 µg/kg of crude scorpion venom, from the 7th to the 13th day of gestation. On the 21st day, the animals were deeply anesthetized using diethyl-ether. Then, blood was collected for chemical parameter analysis. Following euthanasia, morphometric measurements were carried out. The results showed a significant increase in maternal heart and lung absolute weights following venom treatment. However, the mean placental weight per rat was significantly diminished. Furthermore, blood urea concentration was higher in exposed rats (6.97 ± 0.62 mmol/L) than in those receiving saline solution (4.94 ± 0.90 mmol/L). Many organs of venom-treated rat fetuses (brain, liver, kidney and spleen) were smaller than those of controls. On the contrary, fetal lungs were significantly heavier in fetuses exposed to venom (3.2 ± 0.4 g) than in the others (3.0 ± 0.2 g). Subcutaneous blood clots, microphthalmia and total body and tail shortening were also observed in venom-treated fetuses. It is concluded that scorpion envenomation during pregnancy potentially causes intrauterine fetal alterations and growth impairment.(AU)
Assuntos
Animais , Venenos de Escorpião , Teratogênicos/análise , Buthus occitanus , Exposição Materna , Picadas de EscorpiãoRESUMO
In Mexico, maize tortillas are consumed on a daily basis, leading to possible aflatoxin exposure. In a survey of 396 2-kg samples, taken over four sampling days in 2006 and 2007 from tortilla shops and supermarkets in Mexico City, aflatoxin levels were quantified by HPLC. In Mexico, the regulatory limit is 12 µg kg⻹ total aflatoxins for maize tortillas. In this survey, 17% of tortillas contained aflatoxins at levels of 3-385 µg kg⻹ or values below the limit of quantification (
Assuntos
Aflatoxinas/análise , Pão/análise , Carcinógenos/análise , Contaminação de Alimentos , Inspeção de Alimentos/métodos , Sementes/química , Zea mays/química , Pão/economia , Pão/normas , Dieta/etnologia , Manipulação de Alimentos , Fidelidade a Diretrizes , Política de Saúde , Promoção da Saúde , Humanos , Limite de Detecção , México , Mutagênicos/análise , Reprodutibilidade dos Testes , Teratogênicos/análiseRESUMO
This paper is focused in some aspects of maternal exposure to misoprostol during perinatal period, and the abortive and teratogenesis effects on the fetus. The causes of malformations were revised, taking into account chemical, physical and environmental factors as well as the interaction between them. There are evidences that the practice of abortion tripled in Southern and Northeastern Brazil in 15 years, and one of the most frequent forms of abortion is through the use of misoprostol. In Brazil, 1991, 288,700 women were hospitalized as a consequence of complications induced by abortion attempt with this medicine. This fact resulted in the ban of misoprostol across our country, by Decree 344/98 determined by the Health Ministry. The use of misoprostol requires special control and it is allowed only in hospitals, with supervision of the municipal health surveillance. Among the more severe problems affecting the non-aborted child is the injury on the central nervous system, which frequently results in the Moebius syndrome. This is a congenital and non-progressive paralysis of the VI and VII cranial nerves, frequently bilateral, which produces a unexpressive facial appearance and convergent Strabismus. Even banned in our country, abortion is illegally practiced, being deprived of proper knowledge about misoprostol teratogenic effects on the fetus as well as the risks involving mothers.
Este trabalho enfoca aspectos relativos à exposição ao misoprostol no período perinatal como abortificante e agente teratogênico, assim como as causas das malformações, considerando-se fatores químicos, físicos e ambientais. A prática do aborto triplicou nas regiões Sul e Nordeste em 15 anos, sendo que entre os métodos mais freqüentes está o uso do medicamento com o princípio ativo do misoprostol. Em 1991 no Brasil, 288.700 mulheres foram socorridas em hospitais devido a complicações por indução de aborto com este medicamento. Isso resultou na proibição do misoprostol em todo país por determinação da portaria 344/98 do Ministério da Saúde, que exige um controle especial, onde sua utilização é permitida apenas em hospitais e com supervisão da vigilância sanitária municipal. Um dos problemas mais graves que a criança não abortada apresenta é uma injúria em seu sistema nervoso central desenvolvendo a Síndrome de Moebius. Esta é uma paralisia congênita e não progressiva do VI e do VII nervos cranianos, freqüentemente bilateral, que produz uma aparência facial pouco expressiva e estrabismo divergente. Neste sentido, mesmo sendo proibido em nosso país, o aborto induzido por misoprostol é praticado ilegalmente e sem uma verdadeira instrução da paciente sobre os efeitos teratogênicos do mesmo para ela e para seu bebê.