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1.
Toxicol Lett ; 319: 250-255, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31778774

RESUMO

The effect of thalidomide on mandibular development is unclear. In this study, thalidomide was delivered to pregnant rabbits from the 8th to 14th day of gestation. Then, embryos were harvested for examination on the 16th day (GD16), 20th day (GD20) and 24th day (GD24) of gestation. The results showed obvious hemorrhage and hematoma on one side of the craniofacial region in 50 % of the thalidomide-treated embryos and obvious hemorrhage and hematoma on both sides of the craniofacial region in 50 % of the thalidomide-treated embryos at GD16. Histological examination showed soft tissues and mandible defects on the affected side of the maxillofacial region. The expression of Vegf-α, Ki67 and Sox9 on the affected side was significantly down-regulated in comparison to their expression on the unaffected side at GD20. There was also an obvious defect in the affected mandible, and the density of the skull and mandible was decreased compared to the unaffected side or the control group at GD24. These findings demonstrated that thalidomide may lead to hemorrhage and hematoma in the craniofacial region by inhibiting angiogenesis, resulting in the abnormal development of cranial neural crest cells that are involved in the normal development of the mandible in rabbits.


Assuntos
Anormalidades Craniofaciais/induzido quimicamente , Anormalidades Craniofaciais/patologia , Hemorragia/induzido quimicamente , Hemorragia/patologia , Mandíbula/patologia , Neovascularização Fisiológica/efeitos dos fármacos , Teratogênios/toxicidade , Talidomida/toxicidade , Animais , Regulação para Baixo/efeitos dos fármacos , Feminino , Mandíbula/anormalidades , Anormalidades Maxilofaciais/induzido quimicamente , Anormalidades Maxilofaciais/patologia , Crista Neural/patologia , Gravidez , Coelhos , Crânio/anormalidades
2.
Odontology ; 108(1): 1-15, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31172336

RESUMO

The craniofacial complex develops mainly in the first trimester of pregnancy, but its final shaping and the development of the teeth extend into the second and third trimesters. It is intimately connected with the development of the brain because of the crucial role the cranial neural crest cells play and the fact that many signals which control craniofacial development originate in the brain and vice versa. As a result, malformations of one organ may affect the development of the other. Similarly, there are developmental connections between the craniofacial complex and the teeth. Craniofacial anomalies are either isolated, resulting from abnormal development of the first two embryonic pharyngeal arches, or part of multiple malformation syndromes affecting many other organs. They may stem from gene mutations, chromosomal aberrations or from environmental causes induced by teratogens. The craniofacial morphologic changes are generally cosmetic, but they often interfere with important functions such as chewing, swallowing and respiration. In addition, they may cause hearing or visual impairment. In this review we discussed only a small number of craniofacial malformations and barely touched upon related anomalies of dentition. Following a brief description of the craniofacial development, we discussed oral clefts, craniofacial microsomia, teratogens that may interfere with craniofacial development resulting in different malformations, the genetically determined craniosynostoses syndromes and few other relatively common syndromes that, in addition to the craniofacial complex, also affect other organs. The understanding of these malformations is important in dentistry as dentists play an integral role in their diagnosis and multidisciplinary treatment.


Assuntos
Encéfalo , Crista Neural , Feminino , Humanos , Gravidez , Síndrome , Teratogênios
3.
Chemosphere ; 240: 124969, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31726589

RESUMO

The objective of this work was to evaluate whether tetracycline (TC) in environmentally relevant concentrations was able to induce alterations to embryonic development and teratogenic effects in oocytes and embryos of Cyprinus carpio. For this purpose, an embryolethality study was conducted and the lethal concentration 50 (LC50) and effective concentration 50 of malformations (EC50) were calculated, and with these data the teratogenic index (TI) was determined. The main alterations to embryonic development and the teratogenic effects produced by TC on embryos of C. carpio were determined using the Kimmel and Hersem scale adapted for Cyprinus carpio. LC50 and EC50 were respectively 500.08 and 145.3 µg L-1.TC was shown to be teratogenic with teratogenic index of 3.44, and the main malformations identified in concentrations of 90-900 µg L-1 were malformation in tail, modified chorda structure, pericardical edema, scoliosis and malformations of the heart. A significant decrease in concentration-dependent in Kimmel and Hersem score was observed. The results allow us to conclude that TC at environmentally relevant concentrations is capable of inducing embryotoxic and teratogenic effects, generating risk in the integrity of the common carp C. Carpio.


Assuntos
Carpas/embriologia , Desenvolvimento Embrionário/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Teratogênios/farmacologia , Tetraciclina/toxicidade , Animais , Dose Letal Mediana , Teratogênese
4.
Wei Sheng Yan Jiu ; 48(5): 799-806, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31601321

RESUMO

OBJECTIVE: To study the teratogenic effect caused by Xanthoceras sorbifolia Bunge seed on SD rats. METHODS: The experiments were performed in the groups of 2. 0, 4. 0 and 8. 0 g/kg, purified water negative control group and cyclophosphamide positive control group. On the 6 th to 15 th day of pregnancy, the SPF SD rats were exposed to Xanthoceras sorbifolia Bunge seed. All the rats were sacrificed on the day before delivery. Examination were performed on the bones stained by alizarin red and internal organs fixed with Bouins fluid. RESULTS: Maternal body weight, weight gain, uterine fetal weight, net weigh, bed number, corpus luteum number, absorbing births number, live births number, still birth number and percentage and the abnormal rate of appearance, bone, internal organs of each dose group of Xanthoceras sorbifolia, there was no statistical significant difference between Bunge seed groups and negative control group. CONCLUSION: Under the conditions of this experiment, the Xanthoceras sorbifolia Bunge seed had no maternal toxicity to pregnant SD rats, no teratogenic and developmental toxicity to fetal rats. No Observed Adverse Effect Level of maternal toxicity and the minimum teratogenic dose of fetal rats is >8. 0 g/kg.


Assuntos
Extratos Vegetais/toxicidade , Sapindaceae , Teratogênios/toxicidade , Animais , Ratos , Ratos Sprague-Dawley
5.
Int J Nanomedicine ; 14: 4529-4539, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417256

RESUMO

Purpose: Here, we fabricated two plasmonic 2D Ti3C2Tx-based nanocomposites (Au/MXene and Au/Fe3O4/MXene) with similarly high anti-cancer photothermal therapy (PTT) capabilities, but with less in vivo toxicity than a pure MXene. Methods: Au/MXene was synthesized by in situ reduction of tetrachloroauric acid using NaBH4 on Ti3C2Tx flakes. For targeted PTT, magnetic Au/Fe3O4/MXene was synthesized via a reaction between freshly prepared magnetite Fe3O4 NPs and MXene solution, followed by in situ integration of gold nanoparticles (AuNPs). Results: Morphological characterization by XRD, SEM, and TEM revealed the successful synthesis of Au/MXene and Au/Fe3O4/MXene. Both new composites exhibited a significant in vitro dose-dependent PTT effect against human breast cancer cells MCF7. Interestingly, in vivo acute toxicity assays using zebrafish embryos indicated that Au/MXene and Au/Fe3O4/MXene had less embryonic mortality (LC50 ≫ 1000 µg/mL) than pure MXene (LC50=257.46 µg/mL). Conclusion: Our new Au/MXene and Au/Fe3O4/MXene nanocomposites could be safer and more suitable than the pure MXene for biomedical applications, especially when targeted PTT is warranted.


Assuntos
Hipertermia Induzida , Nanocompostos/uso terapêutico , Fototerapia , Titânio/química , Testes de Toxicidade Aguda , Animais , Sobrevivência Celular/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Humanos , Células MCF-7 , Nanocompostos/ultraestrutura , Teratogênios/toxicidade , Difração de Raios X , Peixe-Zebra
6.
Environ Pollut ; 252(Pt B): 1841-1853, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31325757

RESUMO

Nanotechnology and use of nanomaterials (NMs) improve life quality, economic growth and environmental health. However, the increasing production and use of NMs in commercial products has led to concerns about their potential toxicity on human and environment health, as well as its toxicological classification and regulation. In this context, there is an urgent need to standardize and validate procedures for nanotoxicity testing. Since the zebrafish embryotoxicity test (ZET) has been indicated as a suitable approach for the toxicity assessment of traditional and emergent pollutants, the aim of this review is to summarize the existing literature on embryotoxic and teratogenic effects of NMs on zebrafish. In addition, morphological changes in zebrafish embryos induced by NMs were classified in four reaction models, allowing classification of the mode of action and toxicity of different types of NM. Revised data showed that the interaction and bioaccumulation of NMs on zebrafish embryos were associated to several toxic effects, while the detoxification process was limited. In general, NMs induced delayed hatching, circulatory changes, pigmentation and tegumentary alterations, musculoskeletal disorders and yolk sac alterations on zebrafish embryos. Recommendations for nanotoxicological tests are given, including guidance for future research. This review reinforces the use of the ZET as a suitable approach to assess the health risks of NM exposure.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Teratogênios/toxicidade , Testes de Toxicidade/métodos , Peixe-Zebra/embriologia , Animais , Humanos , Projetos de Pesquisa , Peixe-Zebra/crescimento & desenvolvimento
7.
Seizure ; 70: 71-76, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31302303

RESUMO

PURPOSE: After a huge campaign of information on the teratogenic risk of sodium valproate (VPA) having taken place in France we aimed to evaluate the trend of its prescriptions in young epileptic girls. METHOD: Using the French National Health Insurance Database we searched for patients aged 0-14 years being supplied an antiepileptic drug (AED) between 2010 and 2016. RESULTS: 113,362 children received at least one AED, 61,259 boys and 52,103 girls. Compared to 2010-2014 years, VPA was less prescribed in 2016 as first AED (29% vs 37.3% respectively). The difference between the two periods was greater for girls (-41%) than for boys (-12%). CONCLUSION: The changing trend of VPA as first AED prescribed, particularly in girls, reflects published evidence in terms of safety.


Assuntos
Anticonvulsivantes/uso terapêutico , Ácido Valproico/uso terapêutico , Adolescente , Criança , Pré-Escolar , Prescrições de Medicamentos , Feminino , França/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Programas Nacionais de Saúde , Padrões de Prática Médica/tendências , Teratogênios
8.
Food Chem Toxicol ; 131: 110552, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31163220

RESUMO

[OBJECTIVE]: Di(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, may act as an endocrine disruptor and cause developmental toxicity. Differentiated human embryonic stem cells (hESCs) were used to investigate the underlying mechanism of the embryotoxicity induced by DEHP. [Materials and Methods] H9-hESCs were treated with DEHP at different concentrations for 10 days, and the cytotoxicity of DEHP on cell proliferation was determined using a cell-microelectronic sensing technique (Real-Time Cellular Analysis: RTCA). Based on the 50% inhibitory proliferation concentration (IC50), differentiated H9-hESCs were treated with DEHP at 0, 50, 100, and 200 µg/ml for 120 h, followed by measurement of its toxic effects on the transcriptome by mRNA microarray and QuantiGene Plex (QGP). Proteins were detected by the iTRAQ-based proteomics method and the proteins related to the PPARγ/PTEN/Akt pathways were measured by western blotting. The progression of the cell cycle and apoptosis were characterized using flow cytometry (FCM). In other experiments, hESCs were pre-treated with GW9662 (20 µM), a specific PPARγ inhibitor, for 30 min, followed by exposure to GW9662 (20 µM) and DEHP (200 µg/ml) for 120 h to observe the underlying mechanism of DEHP's embryotoxicity. [RESULTS]: DEHP inhibited H9-hESC cell proliferation in a dose-dependent manner, with an IC50 of 165.78 µg/ml. FCM results showed that DEHP could markedly induce cell cycle arrest and increase apoptosis. Gene microarray and QPG array analyses indicated that the peroxisome proliferator-activated receptor γ (PPARγ) was an apparent target for DEHP. We further demonstrated that DEHP could activate the PPARγ and upregulate the expression of PTEN downstream genes, and then play a negative role in the AKT signaling pathway. Cells pretreated with PPARγ inhibitor, GW9662, were shown to restore the effect of DEHP on the PPARγ/PTEN/AKT signaling pathway, and induce the recovery of cell cycle arrest and apoptosis. [CONCLUSION]: DEHP inhibited cell proliferation, promoted cell cycle arrest, and induced apoptosis through the PPARγ/PTEN/AKT signaling pathway in differentiated human embryonic stem cells. It suggested that DEHP exposure possibly cause reproductive or developmental toxicity in humans through the PPARγ signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Dietilexilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Células-Tronco Embrionárias Humanas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Bovinos , Proliferação de Células/efeitos dos fármacos , Emulsões/síntese química , Emulsões/química , Humanos , PPAR gama/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Plastificantes/toxicidade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Soroalbumina Bovina/química , Teratogênios/toxicidade
9.
Biomed Pharmacother ; 117: 109059, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31207578

RESUMO

Jervine is a natural teratogenic compound isolated from Veratrum californicum. In this study, for the first time, we revealed a novel activity of jervine in sensitizing the anti-proliferation effect of doxorubicin (DOX). We demonstrated that the synergistic mechanism was related to the intracellular accumulation of DOX via modulating ABCB1 transportation. Jervine did not affect the expression of ABCB1 in mRNA nor protein levels. However, jervine increased the ATPase activity of ABCB1 and possibly served as a substrate of ABCB1. The molecular docking results indicated that jervine was bound to a closed ABCB1 conformation and blocked drug entrance to the central binding site at the transmembrane domain. The present study identifies jervine acts as a substrate of ABCB1, and has potential to be developed as a novel and potent chemotherapy sensitizer used for patients developing multidrug resistance.


Assuntos
Doxorrubicina/farmacologia , Teratogênios/toxicidade , Alcaloides de Veratrum/toxicidade , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/química , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Células MCF-7 , Estrutura Secundária de Proteína , Especificidade por Substrato/efeitos dos fármacos , Teratogênios/química , Alcaloides de Veratrum/química , Alcaloides de Veratrum/farmacologia
10.
IET Nanobiotechnol ; 13(3): 275-281, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31053690

RESUMO

A facile synthesis of hollow selenium nanoparticles (hSeNPs) was prepared using potato starch as a reducing and capping agent. The morphological and structural characters of the hSeNPs were characterised by ultraviolet-visible spectroscopy (UV), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectroscopy (EDX) and zeta potential analyser. The optical characteristics of hSeNPs were confirmed by UV. The presence of various functional groups in the hSeNPs suspension was confirmed by FTIR. The SEM results suggested that the synthesised hSeNPs were uniformly distributed and circular in shape with a hollow. The average size of the hSeNPs was found to be around 115 nm. The EDX analysis also confirmed the presence of hSeNPs in the sample. The zebrafish embryos were treated with hSeNPs of various concentrations ranging from 10 to 50 µg/ml. Abnormalities such as improper heartbeat, embryo sac oedema, ocular oedema and head oedema were noted at higher concentrations (30-50 µg/ml). A concentration-dependent antioxidant activity of hSeNPs was observed. The hSeNPs showed good antibacterial activity against gram-positive Bacillus subtilis and gram-negative Escherichia coli. The results of this study indicate that potato extract reduces the toxicity of hSeNPs and lower concentrations of hSeNPs could be used for various biomedical applications in near future.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Extratos Vegetais/toxicidade , Selênio/química , Solanum tuberosum/química , Teratogênios/toxicidade , Peixe-Zebra/embriologia , Animais , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Análise Espectral/métodos
11.
Methods Mol Biol ; 1965: 73-91, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31069669

RESUMO

There is widespread interest today in the use of in vitro methods to study normal and abnormal development. The limb is attractive in this context since much is known about pattern formation during limb development. The murine limb bud culture technique described in this chapter was developed and refined in the 1970s. In this culture system, limb development mimics the in vivo process, although at a slower rate, where growth and cartilage differentiation lead to the formation of proximal and distal structures with an "in vivo-like" 3D shape. Uniform developmental stages are selected for assessment, exposures are controlled precisely, and the confounding influences of maternal metabolism and transport are avoided. The existence of transgenic mice with fluorescent markers for the different stages of endochondral ossification adds a further dimension to the technique by allowing striking time course observations of the developing limb. Today, limb bud cultures are used to study the roles of genes during embryogenesis and the mechanisms by which chemicals interfere with critical signalling pathways.


Assuntos
Botões de Extremidades/citologia , Técnicas de Cultura de Órgãos/métodos , Osteogênese , Teratogênios/toxicidade , Animais , Biomarcadores/metabolismo , Diferenciação Celular , Condrogênese , Genes Reporter , Botões de Extremidades/efeitos dos fármacos , Botões de Extremidades/metabolismo , Camundongos , Camundongos Transgênicos , Modelos Biológicos
12.
Methods Mol Biol ; 1965: 155-171, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31069674

RESUMO

The chicken embryo is a versatile and effective model for studying the effects of teratogenic compounds during early development. Easy access to the embryo allows for exposure and analysis of toxicant effects during embryogenesis. This chapter will provide detailed protocols for embryonic collection and toxicant exposure techniques, including EC culture and Cornish Pasty methods, LysoTracker staining, glutathione redox potential analysis, and 2',7'-dichlorodihydrofluorescein diacetate.


Assuntos
Técnicas de Cultura Embrionária/métodos , Desenvolvimento Embrionário/efeitos dos fármacos , Teratogênios/toxicidade , Animais , Embrião de Galinha , Embrião não Mamífero/citologia , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Espécies Reativas de Oxigênio/metabolismo
13.
Methods Mol Biol ; 1965: 187-194, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31069676

RESUMO

The embryotoxicity associated with exposure to exogenous compounds such as drugs and environmental chemicals can be assessed using the mouse whole embryo culture technique. This method has several advantages over traditional in vivo studies including the exclusion of any confounding maternal and placental effects, the selection of embryos that are at similar stages of development, and the control of exposure concentrations of exogenous agents and modifiers of interest. This chapter will detail the steps involved in using this technique to assess embryotoxicity following exposure to a toxicant. Briefly, embryos are explanted from murine dams on gestational day 9.0 (vaginal plug, day 1) and cultured in CO2 saturated male rat serum for up to 24 h at 37 °C in the presence or absence of a specific toxicant. Embryonic morphological and developmental parameters (e.g., anterior neuropore closure) are then evaluated using a dissecting microscope 24 h later. Potential biochemical analyses are also listed and limitations discussed.


Assuntos
Técnicas de Cultura Embrionária/métodos , Desenvolvimento Embrionário/efeitos dos fármacos , Teratogênios/toxicidade , Animais , Meios de Cultura/química , Embrião de Mamíferos/efeitos dos fármacos , Feminino , Masculino , Camundongos , Gravidez , Ratos
14.
Methods Mol Biol ; 1965: 195-217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31069677

RESUMO

The direct effects of chemical exposures, environmental extremes, and nutrient quality/quantity have been very difficult to study in mammalian embryos due to their anatomical inaccessibility, paucity of tissue, and other factors that make human studies unethical. Many acute and chronic developmental anomalies can trace their origins to postimplantation phases of gestation, where the organs are first being established and growth and differentiation are in highly active states of flux. Most chemical insults and conditions that produce birth defects are believed to act during this period of organogenesis. The evolution of rodent whole embryo culture (WEC) techniques has provided a valuable experimental model where physiological conditions and exposures can be carefully controlled and manipulated to test hypotheses and explore biochemical and molecular mechanisms of action that would otherwise be extremely difficult. Exposure to chemicals can be controlled through their direct addition to the culture medium. Optimal in vitro culture conditions support the growth of intact, viable conceptuses (embryo and associated extraembryonic membranes) from early egg cylinder stages through the establishment of the neural plate, gastrulation, neural tube closure, onset of active heartbeat and circulation, and the initial formation of all major organ systems that occur prior to the establishment of a functional placenta. Detailed comparisons of in vivo and in vitro growth show that conceptuses grown in WEC are nearly identical, structurally and functionally, to conceptuses of the same developmental stage that are allowed to develop normally in utero during a comparable developmental period. Culture conditions and mechanical apparatuses can be modified to suit a large number of different experimental approaches and paradigms.


Assuntos
Técnicas de Cultura Embrionária/métodos , Organogênese/efeitos dos fármacos , Teratogênios/toxicidade , Animais , Meios de Cultura/química , Embrião de Mamíferos/efeitos dos fármacos , Feminino , Masculino , Gravidez , Ratos , Testes de Toxicidade
15.
Methods Mol Biol ; 1965: 235-250, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31069679

RESUMO

Environment-gene interactions have a powerful impact on embryo development. The ability to precisely edit the genome makes it possible to address questions concerning the specific roles that genes or variants play in modulating the response to environmental challenges. In this chapter, we provide a simplified protocol using CRISPR-Cas9 ribonucleoproteins for genome editing in the zebrafish model organism. The genetic manipulation can then be coupled with chemical screens to identify and understand the mechanism behind toxicants or compounds that modulate development.


Assuntos
Edição de Genes/métodos , Peixe-Zebra/genética , Animais , Sistemas CRISPR-Cas , Desenvolvimento Embrionário/efeitos dos fármacos , Interação Gene-Ambiente , Teratogênios/toxicidade , Peixe-Zebra/embriologia
16.
Methods Mol Biol ; 1965: 405-420, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31069689

RESUMO

Congenital heart defects (CHD) are the most prevalent anomaly both clinically and in laboratory animal species. Historically, it was difficult to assess the longitudinal progression or repair of such anomalies because assessment methodologies were too invasive (gross exams and/or histology). Recently, technological advances in the field of diagnostic imaging have led to the manufacture of high-resolution ultrasound (HRUS), capable of characterizing both embryonic and maternal cardiovascular structure and function in small animals (rat and mouse). HRUS is relatively noninvasive, facilitating the longitudinal assessment of heart development throughout gestation and postnatally, providing a comprehensive evaluation of changes in cardiovascular performance following toxicant exposure.Described herein is a brief overview of important theoretical and practical considerations when applying HRUS to understand the impact of perturbations on the fetal heart. Examples are given from our own work to help the reader interpret their own HRUS images and more readily identify anomalies in utero. In addition to embryonic assessment, maternal pathologies may adversely affect the cardiovascular performance of the conceptus indirectly. Umbilical blood flow is particularly vulnerable to such effects and procedures to assess this endpoint are described. Neonatal rats, born with CHD, may respond pathologically to cardiovascular challenges as they mature, and we outline the use of HRUS to evaluate cardiac performance over the lifetime of the animal. Some of the caveats related to HRUS are discussed, particularly with the emphasis on how this may impact experimental design.


Assuntos
Ecocardiografia/métodos , Cardiopatias Congênitas/diagnóstico por imagem , Coração/crescimento & desenvolvimento , Teratogênios/toxicidade , Animais , Modelos Animais de Doenças , Feminino , Idade Gestacional , Coração/diagnóstico por imagem , Coração/efeitos dos fármacos , Cardiopatias Congênitas/induzido quimicamente , Camundongos , Gravidez , Ratos , Ultrassonografia
17.
Methods Mol Biol ; 1965: 421-434, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31069690

RESUMO

Teratology is the study of anatomical and physiological abnormalities, commonly known as birth defects. If an embryo is exposed to a harmful substance, or teratogen, during the critical period of development, an ensuing malformation may occur. These malformations and their associated mechanisms are studied and analyzed in laboratory animals in order to prevent them from occurring in humans. Rodents such as rats and mice have commonly been used in such studies because of their similarity to humans. In 1959, James G. Wilson designed, developed, and tested a protocol on how to observe and analyze structural malformations in rodent fetuses, which included: external examination, skeletal evaluation, soft tissue analysis, and data collection/analysis. For standardization purposes, i.e., to normalize findings from one lab to another, it is important that this protocol be followed with precision. Although many years have passed since Wilson initially created this protocol, it is still widely used to this day, and only minor changes have been made to his instructions such as the chemical reagents used in the experiments and methods of analysis of the experimental data. Such testing has resulted in major advances in the dissemination of teratology information, including the identification of an increasing number of teratogens and the understanding of the pathogenesis of birth defects. While mechanistically birth defect prevention will include the understanding of individual genomes and pharmacogenomics, overall, morphological assessment will still be required as an integral part of birth defects research. As the interaction between teratogenic and genetic factors is better understood, it is anticipated that the incidence of most types of defects will substantially be reduced.


Assuntos
Anormalidades Induzidas por Medicamentos/diagnóstico , Anormalidades Congênitas/diagnóstico , Teratogênios/toxicidade , Anormalidades Induzidas por Medicamentos/genética , Animais , Osso e Ossos/anormalidades , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/embriologia , Anormalidades Congênitas/genética , Feminino , Feto/anormalidades , Feto/efeitos dos fármacos , Humanos , Camundongos , Gravidez , Ratos
18.
Environ Sci Pollut Res Int ; 26(19): 19560-19574, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31079296

RESUMO

The current study checks the effect of various concentrations of dietary graphene oxide (GO) nano-sheets on the development of Drosophila melanogaster. GO was synthesized and characterized by XRD, FTIR, FESEM, and TEM analytical techniques. Various concentrations of GO were mixed with the fly food and flies were transferred to the vial. Various behavioral and morphological as well as genetic defects were checked on the different developmental stages of the offspring. In the larval stage of development, the crawling speed and trailing path change significantly than the control. GO induces the generation of oxygen radicals within the larval hemolymph as evidenced by nitroblue tetrazolium assay. GO induces DNA damage within the gut cell, which was detected by Hoechst staining and within hemolymph by comet assay. Adult flies hatched after GO treatment show defective phototaxis and geotaxis behavior. Besides behavior, phenotypic defects were observed in the wing, eye, thorax bristles, and mouth parts. At 300 mg/L concentration, wing spots were observed. Altogether, the current study finds oral administration of GO which acts as a mutagen and causes various behavioral and developmental defects in the offspring. Here for the first time, we are reporting GO, which acts as a teratogen in Drosophila, besides its extensive medical applications.


Assuntos
Drosophila melanogaster/efeitos dos fármacos , Grafite/toxicidade , Mutagênicos/toxicidade , Nanoestruturas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Teratogênios/toxicidade , Administração Oral , Animais , Comportamento Animal/efeitos dos fármacos , Dano ao DNA , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Larva/efeitos dos fármacos , Larva/genética , Larva/crescimento & desenvolvimento
19.
Eur J Med Chem ; 176: 456-475, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31128448

RESUMO

H2S donors are substitutes of H2S with various biological activities like inhibiting the inflammatory response and protecting myocardial cells from injury. In order to confirm whether the H2S donors have drug-like properties, two series thiophosphamide H2S donors were evaluated including toxicity, bioactivity and pharmacokinetic properties in vivo and in vitro. The following results were obtained. Firstly, all the compounds released H2S under measuring condition; with the increase of pH value, the H2S release rate of all the compounds decreased and the amount reduced, but pH value had little effect on the maximum release of H2S. Secondly, in the organs and tissues of rats, the compounds released H2S in the same way as in PBS. In plasma, compound 1 reached the Cmax after administration 55 min, and no compound 1 was detected after 12 h; for compound 18, the Cmax reached only after administration 100 min, and after 6 h, compound 18 was not detected; in organs and tissues, the H2S-release rates were different from those in PBS, but the mechanism of H2S release was the same. Thirdly, in the test of toxicity, all the compounds displayed low toxicities to 5 cancer cells and W138 cell lines; compounds 1 and 18 had slight effect on the physiological tissue and function of rat liver at low concentration; the compounds had almost no effect on the hatching rate, survival rate of zebrafish embryos, and the spontaneous movement of zebrafish embryos at below 0.5 µM, but when they were over 1 µM, the compounds displayed inhibitory effect in the manner of concentration dependence. Fourthly, in the course of anti-inflammatory test, all the tested compounds significantly reduced the level of TNF-α and increased the level of IL-10; when they were 100 µM, the levels of IL-10 were three times as high as those in the control group. Among them, compounds 10 and 18 displayed stronger activities than the others. In addition, the compounds protected H9c2 cells from injure and improved myocardial injury through anti-oxidation pathway. In summary, the compounds have druglike properties due to low toxicity, better activity and good pharmacokinetic property. Therefore, they have potential to be as candidates to investigate further.


Assuntos
Anti-Inflamatórios/farmacocinética , Cardiotônicos/farmacocinética , Sulfeto de Hidrogênio/metabolismo , Compostos Organotiofosforados/farmacocinética , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/toxicidade , Cardiotônicos/síntese química , Cardiotônicos/química , Cardiotônicos/toxicidade , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Feminino , Humanos , Sulfeto de Hidrogênio/sangue , Sulfeto de Hidrogênio/química , Concentração de Íons de Hidrogênio , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Modelos Químicos , Miocárdio/metabolismo , Compostos Organotiofosforados/síntese química , Compostos Organotiofosforados/química , Compostos Organotiofosforados/toxicidade , Células RAW 264.7 , Ratos Wistar , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/patologia , Temperatura Ambiente , Teratogênios/síntese química , Teratogênios/química , Teratogênios/farmacocinética , Teratogênios/toxicidade , Peixe-Zebra
20.
Acta Biochim Pol ; 66(2): 223-228, 2019 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-30980652

RESUMO

A chicken embryo develops in ovo without access to a constant circulating maternal nutrient supply, and therefore all necessary nutrients are initially stored in the yolk, and with progressive development are transferred to the liver, where they are taken up in response to various needs. Fluctuations in hepatic trace elements correlate with their mobilization from egg stores. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) intoxication causes liver damage by production of free radicals, while α-tocopherol is a well-known antioxidant and may play a protective role. In the experiment presented here, a solution containing only TCDD, TCDD and α-tocopherol, as well as α-tocopherol exclusively, was administrated into the yolk sac. The iron, zinc, copper and magnesium distribution was evaluated using histological and chemical methods. It has been found that α-tocopherol has no influence on magnesium and zinc content in the liver. The observed increase in iron content may be caused by antagonistic action of iron and α-tocopherol. On the other hand, synergistic action of α-tocopherol and TCDD has been noted with respect to the copper content.


Assuntos
Fígado/embriologia , Fígado/metabolismo , Dibenzodioxinas Policloradas/toxicidade , Substâncias Protetoras/farmacologia , Teratogênios/toxicidade , Oligoelementos/metabolismo , alfa-Tocoferol/farmacologia , Animais , Embrião de Galinha , Galinhas , Cobre/metabolismo , Feminino , Hepatócitos/patologia , Ferro/metabolismo , Fígado/patologia , Magnésio/metabolismo , Dibenzodioxinas Policloradas/administração & dosagem , Substâncias Protetoras/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Zinco/metabolismo , alfa-Tocoferol/administração & dosagem
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