RESUMO
The morphogenesis of the head of vertebrates is a process that involves rapid growth and dynamic movements of various cell populations, including the neural crest cells (NCC). These pluripotent cells generated during neurulation have high proliferative and migratory capacity but xenobiotic agents can affect these migratory periods and cause congenital malformations. Lead (Pb) is the most common toxic metal in the environment and a potent teratogen that can affect growth and induce malformations. Despite the known toxic effects of Pb, there is a gap in knowledge about the impact of realistic concentrations of Pb at critical periods of early development. Here, we evaluated mortality, embryonic morphology, NCC migration, and the amount of Pb deposition in chicken embryos after 3 to 4 days of exposure. One of the most interesting observations in this study is that only about 34% of the injected Pb was present in the embryos after 4 days. We observed that exposure to Pb, even under low concentrations, increased mortality and the occurrence of malformations during embryonic development, especially in the cephalic region (CR). Although Pb was found widely distributed in the CR, no relation between its presence and the migration routes of cephalic NCC was observed. But the number of NCC and their migratory distance were reduced. These changes are consistent and explain the morphological anomalies described in this study, which also correlates with the morphofunctional abnormalities reported in the literature. Therefore, this study highlights the concern of exposure to low concentrations of this metal.
Assuntos
Intoxicação do Sistema Nervoso por Chumbo/patologia , Crista Neural/patologia , Anormalidades Induzidas por Medicamentos/patologia , Animais , Disponibilidade Biológica , Encéfalo/anormalidades , Encéfalo/patologia , Movimento Celular , Embrião de Galinha , Desenvolvimento Embrionário/efeitos dos fármacos , Chumbo/metabolismo , Chumbo/farmacocinética , Chumbo/toxicidade , Intoxicação do Sistema Nervoso por Chumbo/mortalidade , Morfogênese , Nitratos/toxicidadeRESUMO
ß-ionone (BIO) is used in fragrances, toiletries and non-cosmetic products, and as a flavor food additive. Notwithstanding the widespread human exposure, there are limited data on the reproductive toxicity of BIO. This study evaluated the developmental toxicity of BIO (0, 125, 250, 500 and 1000â¯mg/kg body weight/day) given orally to rats on days 6-15 of gestation (GD6-15). C-section was on GD21 and implantations, living and dead fetuses and resorptions were recorded. Fetuses were weighed, and examined for external abnormalities and skeleton and visceral anomalies. The embryotoxicity of a single oral dose of BIO (1000â¯mg/kg body wt) given on GD11 was evaluated as well. At the highest dose, BIO reduced weight gain and produced chromodacryorrhea and other signs of toxicity. BIO did not increase the frequency of malformations nor did it retard fetal growth. Nonetheless, BIO decreased the pregnancy rate in the group of females exposed on GD6-15, and increased the resorption rate in those treated on GD11 only. In conclusion, except for a higher embryolethality at a maternally toxic dose, BIO caused no embryotoxic effect over the dose range tested and the study NOAEL for maternal and developmental toxicity was 500â¯mg of BIO/ kg of body weight/day.
Assuntos
Norisoprenoides/toxicidade , Aumento de Peso/efeitos dos fármacos , Anormalidades Induzidas por Medicamentos/patologia , Animais , Relação Dose-Resposta a Droga , Feminino , Masculino , Norisoprenoides/administração & dosagem , Norisoprenoides/química , Ratos , Ratos WistarRESUMO
Textile manufacturing is one of the most polluting industrial sectors because of the release of potentially toxic compounds, such as synthetic dyes, into the environment. Depending on the class of the dyes, their loss in wastewaters can range from 2% to 50% of the original dye concentration. Consequently, uncontrolled use of such dyes can negatively affect human health and the ecological balance. The present study assessed the toxicity of the textile dyes Direct Black 38 (DB38), Reactive Blue 15 (RB15), Reactive Orange 16 (RO16), and Vat Green 3 (VG3) using zebrafish (Danio rerio) embryos for 144 h postfertilization (hpf). At the tested conditions, none of the dyes caused significant mortality. The highest RO16 dose significantly delayed or inhibited the ability of zebrafish embryos to hatch from the chorion after 96 hpf. From 120 hpf to 144 hpf, all the dyes impaired the gas bladder inflation of zebrafish larvae, DB38 also induced curved tail, and VG3 led to yolk sac edema in zebrafish larvae. Based on these data, DB38, RB15, RO16, and VG3 can induce malformations during embryonic and larval development of zebrafish. Therefore, it is essential to remove these compounds from wastewater or reduce their concentrations to safe levels before discharging textile industry effluents into the aquatic environment.
Assuntos
Corantes/toxicidade , Resíduos Industriais/efeitos adversos , Indústria Têxtil , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/genética , Anormalidades Induzidas por Medicamentos/patologia , Animais , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/patologia , Embrião não Mamífero/anormalidades , Fertilização , Larva/efeitos dos fármacos , Cauda/patologia , Eliminação de Resíduos Líquidos , Saco Vitelino/efeitos dos fármacosRESUMO
Warfarin is a synthetic oral anticoagulant that crosses the placenta and can lead to a number of congenital abnormalities known as fetal warfarin syndrome. Our aim is to report on the follow-up from birth to age 8 years of a patient with fetal warfarin syndrome. He presented significant respiratory dysfunction, as well as dental and speech and language complications. The patient was the second child of a mother who took warfarin during pregnancy due to a metallic heart valve. The patient had respiratory dysfunction at birth. On physical examination, he had a hypoplastic nose, pectus excavatum, and clubbing of the fingers. Nasal fibrobronchoscopy showed upper airway obstruction due to narrowing of the nasal cavities. He underwent surgical correction with Max Pereira graft, zetaplasty, and osteotomies for the piriform aperture. At dental evaluation, he had caries and delayed eruption of the upper incisors. Speech and language assessment revealed high palate, mouth breathing, little nasal patency, and shortened upper lip. Auditory long latency and cognitive-related potential to auditory stimuli demonstrated functional changes in the cortical auditory pathways. We believe that the frequency of certain findings observed in our patient may be higher in fetal warfarin syndrome than is appreciated, since a significant number result in abortions, stillbirths, or children evaluated in the first year of life without a follow-up. Thus, a multidisciplinary approach and long-term monitoring of these patients may be necessary.
Assuntos
Anormalidades Induzidas por Medicamentos/patologia , Transtornos da Percepção Auditiva/patologia , Osso Nasal/anormalidades , Obstrução Nasal/patologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Anormalidades Dentárias/patologia , Varfarina/efeitos adversos , Anormalidades Induzidas por Medicamentos/genética , Anormalidades Induzidas por Medicamentos/cirurgia , Transtornos da Percepção Auditiva/induzido quimicamente , Transtornos da Percepção Auditiva/genética , Transtornos da Percepção Auditiva/cirurgia , Criança , Feminino , Feto , Seguimentos , Humanos , Masculino , Mães , Osso Nasal/patologia , Osso Nasal/cirurgia , Obstrução Nasal/induzido quimicamente , Obstrução Nasal/genética , Obstrução Nasal/cirurgia , Osteotomia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/cirurgia , Anormalidades Dentárias/induzido quimicamente , Anormalidades Dentárias/genética , Anormalidades Dentárias/cirurgiaRESUMO
PURPOSE: The pathophysiology of abnormalities associated with myenteric plexus lesions remains imperfectly understood. Such abnormalities have been correlated with subocclusive intestinal conditions in children with Hirschsprung's disease, cases of chronic constipation and, postoperatively, in cases of anorectal anomalies. This study evaluated abnormalities of the myenteric plexus in fetus from female rats that received ethylenethiourea. METHODS: Female rats were exposed to ethylenethiourea on the 11(th) day of pregnancy (experimental group) or to 0.9% physiological solution (control group). Abnormalities were only found in the experimental group. The digestive tract muscle layer was analyzed morphometrically and changes to the frequencies of nerve plexus cells and interstitial cells of Cajal were evaluated, using hematoxylin-eosin, S-100 protein, neuron-specific enolase and C-Kit, respectively. RESULTS: Muscle and skeletal abnormalities were observed in 100%, anorectal anomalies in 86%, absent tail in 71%, short tail in 29%, duodenal atresia in 5%, esophageal atresia in 5% and persistent omphalomesenteric duct in 5%. Histopathological analysis showed a thinner muscle layer associated with lower frequencies of ganglion cells and interstitial cells of Cajal, in all gastrointestinal tract. CONCLUSION: Severe nerve plexus abnormalities associated with muscle layer atrophy were observed throughout the gastrointestinal tract in newborn rats exposed to ethylenethiourea.
Assuntos
Anormalidades Induzidas por Medicamentos/patologia , Anormalidades do Sistema Digestório/induzido quimicamente , Etilenotioureia/toxicidade , Atrofia Muscular/induzido quimicamente , Plexo Mientérico/anormalidades , Gravidez/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Músculos Abdominais/inervação , Animais , Animais Recém-Nascidos , Anormalidades do Sistema Digestório/classificação , Anormalidades do Sistema Digestório/patologia , Modelos Animais de Doenças , Feminino , Feto/efeitos dos fármacos , Gânglios/citologia , Células Intersticiais de Cajal/citologia , Atrofia Muscular/patologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Distribuição Aleatória , Ratos , Ratos Wistar , Coloração e Rotulagem/métodos , Estatísticas não ParamétricasRESUMO
PURPOSE: The pathophysiology of abnormalities associated with myenteric plexus lesions remains imperfectly understood. Such abnormalities have been correlated with subocclusive intestinal conditions in children with Hirschsprung's disease, cases of chronic constipation and, postoperatively, in cases of anorectal anomalies. This study evaluated abnormalities of the myenteric plexus in fetus from female rats that received ethylenethiourea. METHODS: Female rats were exposed to ethylenethiourea on the 11th day of pregnancy (experimental group) or to 0.9 percent physiological solution (control group). Abnormalities were only found in the experimental group. The digestive tract muscle layer was analyzed morphometrically and changes to the frequencies of nerve plexus cells and interstitial cells of Cajal were evaluated, using hematoxylin-eosin, S-100 protein, neuron-specific enolase and C-Kit, respectively. RESULTS: Muscle and skeletal abnormalities were observed in 100 percent, anorectal anomalies in 86 percent, absent tail in 71 percent, short tail in 29 percent, duodenal atresia in 5 percent, esophageal atresia in 5 percent and persistent omphalomesenteric duct in 5 percent. Histopathological analysis showed a thinner muscle layer associated with lower frequencies of ganglion cells and interstitial cells of Cajal, in all gastrointestinal tract. CONCLUSION: Severe nerve plexus abnormalities associated with muscle layer atrophy were observed throughout the gastrointestinal tract in newborn rats exposed to ethylenethiourea.
OBJETIVO: As anomalias associadas a lesões dos plexos mioentéricos permanecem sem plena compreensão da sua fisiopatologia. Alterações nos plexos nervosos têm sido correlacionadas com quadros suboclusivos intestinais em crianças portadoras de doença de Hirschsprung, em constipação crônica e no pós-operatório de anomalias anorretais. Este estudo avaliou as anomalias do plexo mioentérico em fetos de ratos fêmea que ingeriram etilenotioureia (ETU). MÉTODOS: Ratos fêmea foram expostos no 11º dia de gestação a ETU 1 por cento no Grupo Experimento e a solução fisiológica 0,9 por cento no Grupo Controle. Foram observadas anomalias apenas no Grupo experimento, sendo realizada morfometria da camada muscular e avaliadas alterações da frequência celular nos gânglios do plexo mioentérico e nas células intersticiais de Cajal (CIC) utilizando hematoxilina-eosina, P S-100, Enolase Neurônio Específica e C-KIT. RESULTADOS: Foram observadas anomalias musculoesqueléticas (100 por cento), anorretais (86 por cento), ausência de cauda (71 por cento), cauda curta (29 por cento), atresia duodenal (5 por cento), atresia esofágica (5 por cento) e conduto onfalomesentérico persistente (5 por cento). A análise histopatológica mostrou adelgaçamento da camada muscular associada às alterações da frequência das células ganglionares e das CIC em todos os segmentos do trato gastrointestinal. CONCLUSÃO: Foram observadas alterações graves nos plexos nervosos associadas ao adelgaçamento da camada muscular de todo o trato gastrointestinal nos fetos expostos a ETU.
Assuntos
Animais , Feminino , Ratos , Anormalidades Induzidas por Medicamentos/patologia , Anormalidades do Sistema Digestório/induzido quimicamente , Etilenotioureia/toxicidade , Atrofia Muscular/induzido quimicamente , Plexo Mientérico/anormalidades , Gravidez/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Animais Recém-Nascidos , Músculos Abdominais/inervação , Modelos Animais de Doenças , Anormalidades do Sistema Digestório/classificação , Anormalidades do Sistema Digestório/patologia , Feto/efeitos dos fármacos , Gânglios/citologia , Células Intersticiais de Cajal/citologia , Atrofia Muscular/patologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Distribuição Aleatória , Ratos Wistar , Estatísticas não Paramétricas , Coloração e Rotulagem/métodosRESUMO
BACKGROUND: Maternal hyperglycemia during early pregnancy is associated with increased risk of abnormalities in the offspring. Malformation rates among the offspring of diabetic mothers are 2-5-fold higher than that of the normal population, and congenital malformations are the major cause of mortality and morbidity in the offspring of diabetic mothers. Metabolic changes, such as hyperglycemia and the metabolites obtained from cigarettes both increase the production of reactive oxygen species (ROS) in the embryo or fetus, causing DNA damage. OBJECTIVE: To evaluate the maternal and fetal genotoxicity, and to assess the incidence of fetal anomaly in diabetic female rats exposed to cigarette smoke at different stages of pregnancy in rats. MATERIAL AND METHOD: Diabetes was induced by streptozotocin administration and cigarette smoke exposure was produced by a mechanical smoking device that generated mainstream smoke that was delivered into a chamber. Female Wistar rats were randomly assigned to: non-diabetic (ND) and diabetic (D) groups exposed to filtered air; a diabetic group exposed to cigarette smoke prior to and during pregnancy (DS) and a diabetic group only exposed to cigarette smoke prior to pregnancy (DSPP). On pregnancy day 21, blood samples were obtained for DNA damage analysis and fetuses were collected for congenital anomaly assessment. Statistical significance was set at p<0.05 for all analysis. RESULTS AND CONCLUSION: Exposure of diabetic rats to tobacco smoke prior to pregnancy increased fetal DNA damage, but failed to induce teratogenicity. Thus, these results reinforce the importance for women to avoid exposure to cigarette smoke long before they become pregnant.
Assuntos
Anormalidades Induzidas por Medicamentos/patologia , Dano ao DNA , Diabetes Mellitus Experimental/fisiopatologia , Feto/efeitos dos fármacos , Exposição Materna , Gravidez em Diabéticas/fisiopatologia , Poluição por Fumaça de Tabaco/efeitos adversos , Anormalidades Induzidas por Medicamentos/sangue , Anormalidades Induzidas por Medicamentos/embriologia , Anormalidades Induzidas por Medicamentos/etiologia , Animais , Câmaras de Exposição Atmosférica , Ensaio Cometa , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Feto/patologia , Hiperglicemia/etiologia , Leucócitos/efeitos dos fármacos , Leucócitos/patologia , Gravidez , Gravidez em Diabéticas/sangue , Distribuição Aleatória , Ratos , Ratos Wistar , Fumar/efeitos adversos , Fumar/sangue , Fumar/patologia , EstreptozocinaRESUMO
O objetivo deste trabalho é relatar um caso de reconstrução nasal precoce em um paciente com síndrome do Warfarin fetal, onde um paciente de 23 dias com apresentava hipoplasia nasal isolada. O ganho ponderal estava estagnado e não havia possibilidade de introdução de sonda nasoentérica devido à deformidade. Foi realizada rinoplastia aberta com incisão transcolumelar. Dois enxertos de cartilagem tragal foram confeccionados e introduzidos na região da ponta, porção cranial do septo cartilaginoso e alares. O paciente apresentou melhoria da permeabilidade ventilatória, diminuição do ruído inspiratório, ganho de peso e também da forma. Após um ano de seguimento o resultado continuava satisfatório. Concluímos que a intervenção precoce é satisfatória e pode minimizar ou mesmo prevenir procedimentos futuros.
The aim of this work is to report a case of early nasal reconstruction in a 23-day-old patient with fetal Warfarin syndrome and isolated nasal hypoplasia. Weight gain was arrested and the deformity precluded the use of a nasogastric tube. An open rhinoplasty with transcolumellar incision was performed. Two grafts of tragal cartilage were made and introduced in the tip area, cranial portion of the cartilaginous septum, and alar cartilages. The patient presented improved ventilatory permeability, decrease of inspiratory noise, and weight and shape gains. At the one-year follow-up the result was still satisfactory. We concluded that early intervention is satisfactory and may minimize or even prevent future procedures.
Assuntos
Humanos , Anormalidades Induzidas por Medicamentos/genética , Anormalidades Induzidas por Medicamentos/patologia , Rinoplastia , Varfarina , Varfarina/efeitos adversos , Anormalidades Maxilofaciais , Anticoagulantes/efeitos adversos , Doenças Fetais/cirurgia , Doenças Fetais/genética , Doenças Fetais/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/cirurgia , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamenteRESUMO
Maternal epilepsy has a potential for fetal injury, either antiepileptic drug (AED)--induced or as a consequence of seizures per se. The intent of this article is to explore this relationship, discussing similar patterns of malformations seen with AEDs or different disease exposure during pregnancy, and the potential role of gap junctional intercellular communication in abnormal morphogenesis.
Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Anticonvulsivantes/efeitos adversos , Encéfalo/anormalidades , Efeitos Tardios da Exposição Pré-Natal/patologia , Anormalidades Induzidas por Medicamentos/patologia , Encéfalo/embriologia , Feminino , Humanos , GravidezRESUMO
Evidence suggests that Angiotensin II plays an important role in the complex process of renal organogenesis. Rat kidney organogenesis starts between E13-14 and lasts up to 2 weeks after birth. The present study demonstrates histologic modifications and changes in receptor localisation in animals born from mothers treated with Angiotensin II, Losartan or PD123319 (1.0 mg/kg/day) during late pregnancy. Angiotensin II-treated animals exhibited very well developed tubules in the renal medulla in coincidence with higher AT(1) binding. Control animals exhibited angiotensin AT(2) binding in the outer stripe of the outer medulla, while in the Angiotensin II-treated animals binding was observed to the inner stripe. In Angiotensin II-treated 1-week-old animals, the nephrogenic zone contained fewer immature structures, and more developed collecting tubules than control animals. Treatment with Losartan resulted in severe renal abnormalities. For newborn and 1-week-old animals, glomeruli exhibited altered shape and enlarged Bowman spaces, in concordance with a loss of [(125)I]Angiotensin II binding in the cortex. Blockade with PD123319 led to an enlarged nephrogenic zone with increased number of immature glomeruli, and less glomeruli in the juxtamedullary area. Autoradiography showed a considerable loss of AT(1) binding in the kidney cortex of PD123319-treated animals at both ages. The present results show for the first time histomorphological and receptor localisation alterations following treatment with low doses of Losartan and PD123319 during pregnancy. These observations confirm previous assumptions that in the developing kidney Angiotensin II exerts stimulatory effects through AT(1) receptors that might be counterbalanced by angiotensin AT(2) receptors.
Assuntos
Anormalidades Induzidas por Medicamentos/patologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/toxicidade , Bloqueadores do Receptor Tipo 2 de Angiotensina II , Rim/anormalidades , Prenhez/fisiologia , Envelhecimento/metabolismo , Angiotensina II/antagonistas & inibidores , Angiotensina II/farmacologia , Animais , Animais Recém-Nascidos , Autorradiografia , Feminino , Imidazóis/toxicidade , Rim/patologia , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/patologia , Losartan/toxicidade , Gravidez , Piridinas/toxicidade , Ratos , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologiaAssuntos
Feminino , Humanos , Recém-Nascido , Gravidez , Anormalidades Induzidas por Medicamentos/patologia , Antitireóideos/efeitos adversos , Atresia das Cóanas/induzido quimicamente , Metimazol/efeitos adversos , Atresia das Cóanas/patologia , Doença de Graves/tratamento farmacológico , Troca Materno-Fetal , Complicações na Gravidez/tratamento farmacológicoAssuntos
Anormalidades Induzidas por Medicamentos/patologia , Antitireóideos/efeitos adversos , Atresia das Cóanas/induzido quimicamente , Metimazol/efeitos adversos , Atresia das Cóanas/patologia , Feminino , Doença de Graves/tratamento farmacológico , Humanos , Recém-Nascido , Troca Materno-Fetal , Gravidez , Complicações na Gravidez/tratamento farmacológicoRESUMO
The effect of glycine in preventing cadmium (Cd) teratogenicity in mice was studied. Cadmium chloride (CdCl2) was administered subcutaneously at 1, 2 or 4 mg/kg doses on gestation days (GD) 7, 8 and 9. Glycine was given ad libitum (in the drinking water) from GD0 through GD18 (the day when animals were killed), as a 1% and 2% drinking water solution. Cd and nucleic acid concentrations in embryos were determined. The most common finding seen after CdCl2 4 mg/kg exposure was exencephaly. The incidence of this malformation was significantly reduced in mice receiving 2% glycine while fetal Cd significantly decreased as compared to cadmium-treated positive control animals. Increased nucleic acid levels were seen in the same embryos. In glycine non-supplemented mice given CdCl2 4 mg/kg, embryonic lipid peroxidation proved to be increased. In conclusion, lipid peroxidation was associated with cadmium-induced teratogenicity, and glycine inhibited the cadmium-induced effect by inhibiting placental transport of cadmium. However, further detailed studies are needed to establish the mechanism(s) of action.
Assuntos
Anormalidades Induzidas por Medicamentos/prevenção & controle , Cloreto de Cádmio/toxicidade , Embrião de Mamíferos/efeitos dos fármacos , Glicina/farmacologia , Teratogênicos/toxicidade , Anormalidades Induzidas por Medicamentos/patologia , Animais , DNA/análise , Relação Dose-Resposta a Droga , Antagonismo de Drogas , Embrião de Mamíferos/anormalidades , Embrião de Mamíferos/metabolismo , Feminino , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Camundongos , GravidezRESUMO
BACKGROUND: The concomitant occurrence of breast cancer and pregnancy is relatively uncommon. We report the case of a patient with syndactyly, cleft hands, and absence of distal finger phalanges associated with maternal exposure to chemotherapeutic agents during the first trimester of pregnancy. These associations have not been previously described. CASE: The patient was born by normal delivery after 38 weeks of pregnancy. His mother became pregnant while receiving chemotherapy (cyclophosphamide, 5-fluorouracil, and adriamycin) for breast cancer, and the fetus was exposed to these drugs from conception to the 16th week of pregnancy. At birth, anomalies were observed, including a high-arched palate, microcephaly, a flat nasal bridge, bilateral syndactyly in the first and second fingers with a hand cleft between the second and third fingers and hypoplasia of the fifth fingers, and dystrophic nail of the fourth finger of the left hand. The patient's growth and development were deficient. CONCLUSIONS: The malformations associated with in utero exposure to these chemotherapeutic agents are highly variable, but growth deficiency and anomalies of the craniofacial region and limbs are the most common. The pattern of malformations in children who were congenitally exposed to chemotherapeutic agents appears to be directly related to the age at and duration of exposure, rather than to the specific drug itself. Effective contraception is essential for the safe use of a potential teratogen in nonpregnant women of reproductive age.
Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Anormalidades Múltiplas/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Neoplasias da Mama/tratamento farmacológico , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Teratogênicos/toxicidade , Anormalidades Induzidas por Medicamentos/diagnóstico por imagem , Anormalidades Induzidas por Medicamentos/patologia , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/patologia , Adulto , Antibióticos Antineoplásicos/toxicidade , Antimetabólitos Antineoplásicos/toxicidade , Antineoplásicos Alquilantes/toxicidade , Pré-Escolar , Ciclofosfamida/toxicidade , Deficiências do Desenvolvimento/induzido quimicamente , Doxorrubicina/toxicidade , Quimioterapia Combinada , Feminino , Fluoruracila/toxicidade , Humanos , Masculino , Troca Materno-Fetal/efeitos dos fármacos , Microcefalia/induzido quimicamente , Gravidez , Complicações Neoplásicas na Gravidez/etiologia , Terceiro Trimestre da Gravidez , Radiografia , Sindactilia/diagnóstico por imagem , Sindactilia/etiologiaRESUMO
Diphenyl diselenide is an organoselenium compound with potential therapeutic use. The present study evaluates the effects of single maternal subcutaneous injection of 50 and 100mg/kg diphenyl diselenide [(PhSe)2] at gestational days (GD) 6, 10 or 17 in Wistar rats. The highest dose of (PhSe2 was also administered at GD 7-12. External and internal fetal soft-tissue examination was performed at GD 20. No mortality was observed in fetuses or dams at any (PhSe)2 treatment group. Neither did exposure to (PhSe)2 cause significant changes to fetal body weight, organ weight, or fetal size when administered at GD 6-8, 10-12 or 17. Exposure to 100mg/kg (PhSe)2 at GD 9 produced significant changes in fetal biometry (crown-rump (CR) length) and body weight. No significant increase in the proportion of fetuses with external visible abnormalities was observed in groups exposed to (PhSe)2. Skeletal anomalies were observed in fetuses in the GD 9-11 treatment groups and included incomplete ossification of cranial bones, misshapen and incomplete ossification of sternebrae, reduced sternebrae number, wavy and extra ribs, incomplete ossification of fore and hindpaw bones and incomplete ossification of sacral and caudal bones. We conclude that maternal administration of (PhSe)2 during GD 7-12 led to increased incidences of these skeletal variations or anomalies, but did not cause externally visible malformations in rat fetuses.
Assuntos
Anormalidades Induzidas por Medicamentos/patologia , Antioxidantes/toxicidade , Derivados de Benzeno/toxicidade , Compostos Organosselênicos/toxicidade , Animais , Antioxidantes/administração & dosagem , Derivados de Benzeno/administração & dosagem , Osso e Ossos/anormalidades , Relação Dose-Resposta a Droga , Feminino , Retardo do Crescimento Fetal/induzido quimicamente , Feto/efeitos dos fármacos , Idade Gestacional , Deformidades Congênitas dos Membros/patologia , Troca Materno-Fetal , Compostos Organosselênicos/administração & dosagem , Osteogênese/efeitos dos fármacos , Gravidez , Ratos , Ratos WistarRESUMO
Lantana camara L. (Verbenaceae) possesses several medicinal properties and it is used in folk medicine with antipyretic, antimicrobial and antimutagenic properties. This plant is one of the 10 most noxious weeds in the world. Lantana poisoning have caused severe economic losses and was the major cause of livestock mortality and morbidity. In this article we report the effects of hydroalcoholic extract from Lantana camara var. aculeata leaves on fertility, general reproductive performance and teratology in the rat. The data showed that the extract interfered in the frequency of fetal skeleton anomalies from dams treated with the extract and induced embryotoxicity as indicated by post-implantation loss, without any signs of maternal toxicity. The other parameters evaluated did not suggest modifications.
Assuntos
Anormalidades Induzidas por Medicamentos/patologia , Fertilidade/efeitos dos fármacos , Crescimento e Desenvolvimento/efeitos dos fármacos , Lantana/química , Reprodução/efeitos dos fármacos , Animais , Peso Corporal , Brasil , Feminino , Troca Materno-Fetal , Tamanho do Órgão , Extratos Vegetais/toxicidade , Gravidez , Ratos , Ratos WistarRESUMO
Although exposure to cyanogenic plants or cyanide during pregnancy has adverse effects, no teratological study with cyanide has been conducted in goats or any other ruminant. The objective of the present study was to evaluate the effects of the maternal exposure to potassium cyanide (KCN) during pregnancy on both dams and offspring and furthermore, to develop a model for prenatal toxicological studies in ruminants. Twenty-six pregnant goats were allocated into four groups and given 0, 1.0, 2.0, or 3.0mg KCN/kg body weight per day orally (administered via twice-daily gavage) from Day 24 of pregnancy to term. However, one control dam and another from the 3.0mg KCN/kg per day group were sacrificed on Day 120. At birth, the kids were examined carefully for gross abnormalities. Three months after birth, the male kids and one dam from each group were sacrificed for histopathological study. Although clinical signs of poisoning were observed in dams, cyanide treatment did not alter the length of gestation or the number of live kids. Two prognata kids were born in the 3.0mg KCN/kg group, and one dam from the same group aborted two fetuses. There were histological lesions only in the KCN-treated dam (and its fetuses) sacrificed on Day 120; these consisted of an increased number of resorption vacuoles of thyroid follicular colloid, and status spongiosis of nervous white matter. This study proposes a new animal model for teratogenic trials that could be important to evaluate the effects of chemicals throughout pregnancy in goats and potentially other ruminants.
Assuntos
Anormalidades Induzidas por Medicamentos , Cabras , Modelos Animais , Cianeto de Potássio/toxicidade , Ruminantes , Anormalidades Induzidas por Medicamentos/patologia , Animais , Feminino , Morte Fetal/epidemiologia , Morte Fetal/veterinária , Masculino , Cianeto de Potássio/administração & dosagem , Gravidez , Glândula Tireoide/anormalidades , Glândula Tireoide/patologia , Tiroxina/sangue , Tri-Iodotironina/sangueAssuntos
Anormalidades Induzidas por Medicamentos/veterinária , Anuros/anormalidades , Exposição Ambiental , Glicina/análogos & derivados , Glicina/toxicidade , Herbicidas/toxicidade , Poluentes Químicos da Água/toxicidade , Anormalidades Induzidas por Medicamentos/patologia , Animais , Larva/crescimento & desenvolvimento , Dose Letal Mediana , Mortalidade , GlifosatoRESUMO
In the amphibian Ambystoma mexicanum, valproic acid (VPA) causes retarded development and malformations including neural tube defects. Some of the observed abnormalities resemble exencephaly. We present the light microscopic characteristics of VPA-induced effects on the developing central nervous system (CNS) as well as on other developing tissues of this species. To induce malformations, various concentrations of VPA were applied to embryos from blastula stage on, either as 24-h pulse or as continuous exposure. In treated embryos the abnormal development of the CNS was indicated by retarded neurulation and disturbed closure of the neural folds. Furthermore, the neural epithelium was disorganized and its cells were less elongated than normal. Two ventricle lumina of various shapes arose in the neural tube and the neural epithelium extended laterally, whereas in the control animals the neural tube was small and overlaid the notochord only. In treated embryos intercellular spaces in neural epithelium as well as in connective tissue were enlarged and cell adhesion seemed disturbed in both tissues. The notochord underlying the neural plate appeared to be normally organized but oversized somites appeared, which periodically filled the space between notochord and notoplate. VPA also affected neural crest cells. Additional effects occurring were edema and liver damage. A high concentration of VPA even stopped development in early gastrulation. Characteristics of induced effects indicate an interaction between the drug and components of the extracellular matrix and the cytoskeleton.
Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Anticonvulsivantes/toxicidade , Sistema Nervoso Central/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Teratogênicos/toxicidade , Ácido Valproico/toxicidade , Anormalidades Induzidas por Medicamentos/patologia , Ambystoma/embriologia , Animais , Sistema Nervoso Central/anormalidades , Sistema Nervoso Central/embriologia , Relação Dose-Resposta a Droga , Epitélio/efeitos dos fármacos , Epitélio/patologia , Fígado/anormalidades , Fígado/efeitos dos fármacos , Fígado/patologia , Fatores de TempoRESUMO
The evidence presented here strengthens the argument that RA-induced truncation defects of the embryonic limb, and probably other teratogenic effects, are mediated by the nuclear retinoid receptors, particularly the RAR-beta 2 isoform. Although apoptotic cell death and an increased transglutaminase (tTG) activity accompany teratogenesis, it should be emphasized that the increased levels of RAR-beta 2 may influence additional events in limb development, e.g., modulation of connective tissue differentiation and an inhibition of chondrogenesis. Further work entails screening the effects of RA on genes targeted by the receptors.