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1.
Environ Toxicol Chem ; 43(9): 1996-2004, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38980319

RESUMO

In 2019, there was an environmental catastrophe in Brazil, when more than 5000 tons of unknown origin crude oil invaded beaches and mangroves. Two years later, two monitoring areas were selected to study seahorses' offspring: Massangana River estuary (apparently healthy area) and Cocaia Island (affected area). Thirty-six reproductive events of Hippocampus reidi (Syngnathidae) couples from these two areas were monitored to analyze the offspring. At the apparently healthy area, no newborns with malformations were found. However, the offspring from Cocaia Island showed a mean of 19.73% (±5.23) malformations in newborns. It is argued that the toxic/teratogenic effects of polycyclic aromatic hydrocarbons have affected the population in two ways: directly through the induction of mutations in the germ cells of the species and through a drastic reduction of the population (bottleneck effect) whose density observed today recovered through consanguineous couplings, potentiating deleterious genotypes in the offspring. Environ Toxicol Chem 2024;43:1996-2004. © 2024 SETAC.


Assuntos
Poluição por Petróleo , Smegmamorpha , Poluentes Químicos da Água , Animais , Brasil , Poluentes Químicos da Água/toxicidade , Masculino , Feminino , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Monitoramento Ambiental
2.
Artigo em Inglês | MEDLINE | ID: mdl-37844749

RESUMO

The mixture of agrochemicals can be made to improve pest control or accidentally. In this way, the effects on non-target organisms are a critical aspect of the environment and heath. Thus, this work aimed to show how a mixture of pyriproxyfen, and glyphosate can impair biochemical routes and embryonic development. Zebrafish embryos 0-72 hpf were exposed to 0.001-1 µg/mL of pyriproxyfen, glyphosate, and a mixture of both pesticides. The ADMETox was evaluated in silico. The FET-test was used to estimate teratogenic effects. The biochemical effects were estimated using AChE, SOD, and CAT as parameters. ROS generation was estimated using 30 µM H2DCF-DA and 5 µM DHE. The ADMETox reveals that intestinal absorption and P-glycoprotein are the main sites for PPx and Gly adsorption. The distribution parameters were diverse. PPx + Gly at 0.1 µg/mL leads to 50 % of lethality and at 1 µg/mL 100 % of lethality. PPx + Gly leads to a 22 % of lack of somite formation at 1 µg/mL. The heart rate was reduced by >10 % in all concentrations tested. The AChE has a decrease with IC20 19.6 µM and IC50 261.5 µM. SOD showed a reduction of 28 % to PPx and CAT was reduced by 58 % to PPx + Gly and Gly at 1 µg/mL. Glyphosate does not increase unspecific ROS generation. The superoxide generation was 2× higher in the PPx + Gly at 1 µg/mL. Summarily, was observed that the mixture of PPx + Gly potentiated the toxic effects. This finding suggests a possible synergism between the PPx and Gly even at lower concentrations.


Assuntos
Superóxido Dismutase , Peixe-Zebra , Animais , Espécies Reativas de Oxigênio , Glifosato
3.
J Toxicol Environ Health A ; 86(16): 543-556, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37340982

RESUMO

Alternanthera littoralis P. Beauv is a plant native to Brazil that exhibits various beneficial activities including antioxidant, antibacterial, antifungal, antiprotozoal, anti-hyperalgesic, and anti-inflammatory properties. The aim of this study was to assess the impact of the ethanol extract of Alternanthera littoralis (EEAl) on reproductive outcomes, embryofetal development, and DNA integrity of pregnant female mice. Pregnant Swiss female mice were randomly assigned to three experimental groups (n = 10): controls were administered either 1% Tween 80 (vehicle), EEAl 100 mg/kg or EEAl 1000 mg/kg. Treatment was administered through gavage during the gestational period until day 18. On gestational days 16, 17, and 18, a peripheral blood sample from the tail vein was obtained for DNA integrity analysis (micronucleus test). After the last collection, animals were euthanized by cervical dislocation. Maternal organs and fetuses were collected, weighed, and subsequently analyzed. Reproductive outcome parameters were assessed by measurement of number of implants, live fetuses, and resorptions. Embryonic development was determined by adequacy of weight for gestational age as well as determination of external, visceral, and skeletal malformations. Data demonstrated that EEAl did not produce maternal toxicity at either dose associated with no marked alterations in any of the reproductive outcome parameters including implantation sites, live/dead fetuses ratio, fetal viability, post-implantation losses, resorptions, and resorption rate. However, EEAl 1000 group reduced embryofetal development by lowering placental weight. In addition, there was an increase in the frequency of external and skeletal malformations in the EEAl 1000 group, which could not be attributed to extract exposure as these values were within control levels. Based upon our findings, evidence indicates that the EEAl at the concentrations employed in our study may be considered safe for use during pregnancy and extracts of this plant show potential for development of phytomedicines to be used in pregnancy.


Assuntos
Anormalidades Induzidas por Medicamentos , Placenta , Animais , Feminino , Camundongos , Gravidez , DNA/farmacologia , Etanol , Feto , Idade Gestacional , Reprodução
4.
Environ Toxicol Pharmacol ; 100: 104144, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37149012

RESUMO

Iron oxide nanoparticles (IONP) are promising alternatives to environmental remediation, so this study investigates IONP single and associated to contaminants, in this case, glyphosate (GLY) and Roundup® (GBH) in Poecilia reticulata (guppy). The guppies have internal development, therefore this study analyzed female gonads to establish the developmental stages of P. reticulata and evaluate effects of exposure (7, 14 and 21 days) and post-exposure (same period) to the treatments with Iron ions 0.3 mg Fe/L (IFe); IONP 0.3 mg Fe/L; IONP 0.3 mgFe/L + GBH 0,65 mgGLY/L (IONP+GBH1); IONP 0.3 mgFe/L + GBH 1.30 mgGLY/L (IONP+GBH2); and IONP 0.3 mgFe/L + GLY 0.65 mg/L (IONP+GLY). The development was organized in immature, development, and gestation phases. The damage in all treatments after 21 days of exposure was evident in reaction patterns regressive inflammatory, and circulatory including total histopathologic index of liver, nevertheless there was a damage recovery trend during post-exposure period.


Assuntos
Ovário , Poecilia , Animais , Feminino , Fígado , Nanopartículas Magnéticas de Óxido de Ferro , Glifosato
5.
BMC Complement Med Ther ; 23(1): 145, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37143000

RESUMO

Salvia lachnostachys Benth is native to Brazil and has anti-inflammatory, anti-arthritic, cytotoxic, antitumor, and antihyperalgesic activities. The population, including pregnant women, consume this plant to treat pain, inflammation, flu, spasms, insomnia, and depression, mainly. There are no safety reports on the use of this plant during pregnancy. The present study aimed to evaluate the effects of S. lachnostachys ethanolic extract (EESl) on reproductive performance, embryofetal development, and DNA integrity of pregnant female mice. Pregnant females were randomly divided into three experimental groups (n = 10): The Control group was treated with a vehicle, and treatment groups were administered with EESl at 100 and 1000 mg/kg, respectively. Treatment occurred by gavage throughout the gestational period until day 18. Afterward, reproductive performance, embryofetal development, and DNA integrity parameters were evaluated. The results indicated that EESl did not alter any reproductive performance parameters. However, it changed embryofetal outcome through reduced placental weight (EESl 100 mg/kg), decreased fetal weight (EESl 100 and 1000 mg/kg), and increased frequency of small for gestational age fetuses (EESl 1000 mg/kg). In addition, EES1 increased the frequency of external, visceral, and skeletal malformations. Because of the above, it is considered that EESl is not maternotoxic, does not alter reproductive performance, but does alter embryofetal development. Its use in the gestational period is not indicated due to its teratogenic potential.


Assuntos
Salvia , Teratogênicos , Humanos , Gravidez , Feminino , Camundongos , Animais , Placenta , Etanol , Extratos Vegetais/toxicidade , DNA
6.
Pharmaceutics ; 14(11)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36365187

RESUMO

Gomphrena celosioides is a native Brazilian plant found in the State of Mato Grosso do Sul. It is used in folk medicine to treat kidney diseases, skin diseases, infections, rheumatism, gastrointestinal diseases, and respiratory diseases. It is also used as an abortifacient. To evaluate the effects of the ethanolic extract of Gomphrena celosioides (EEGc) on reproductive performance, embryo development, and chromosome stability, Swiss mice were randomly divided into experimental groups (n = 10). The animals in the control group received the vehicle Tween 80-1% in the proportion of 0.1 mL/10 g of body weight orally, from the first to the 18th gestational day. The animals in the treatment groups received the EEGc (100, 1000, and 2000 mg/kg) from the first to the 18th gestational day. The animals underwent evaluations of their reproductive performance and embryofetal development. The results showed that the EEGc did not change the animals' final weight, weight gain, uterine weight, or net weight gain. The evaluation showed that the absolute and relative organs' weights did not vary between the different experimental groups. In addition, the EEGc did not change the numbers of implants, live fetuses, dead fetuses, or fetal resorptions. There were no differences in post-operative loss rates, implantations, or resorptions, nor were there differences in fetal viability or sex ratio. The use of the EEGc did not result in different frequencies of malformations. In addition, the EEGc did not alter the frequency of chromosomal damage or frequency of micronuclei. Based on our findings, we considered the extract of Gomphrena celosioides to be safe for use during pregnancy, although some parameters indicated caution in its use.

7.
Birth Defects Res ; 114(20): 1354-1363, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36177858

RESUMO

BACKGROUND: HAND2 is a transcription factor important for embryonic development, required for limbs and cardiovascular development. Thalidomide is a drug responsible to a spectrum of congenital anomalies known as Thalidomide Embryopathy (TE), which includes mainly limb and heart defects. It is known that HAND2 interaction with TBX5, an important protein for limbs and heart development, is inhibited by Thalidomide. The aim of this study was to evaluate and characterize HAND2 in the context of TE, and to evaluate its variability in TE individuals. METHODS: DNA from 35 TE subjects was extracted from saliva samples and PCR was performed for amplification and Sanger sequencing of HAND2 coding sequence. RESULTS: The analysis showed only one variant; a synonymous variant p.P51 (rs59621536) in exon 1 found in three individuals. Further in silico evaluation confirmed highly HAND2 conservation, being the 3'UTR the most polymorphic region of the gene. Additional computational analyses classified the variant as neutral, without alteration in splicing and miRNA sites. In silico predictions pointed to alteration of two CpG islands adjacent to the variant; however, we did not observe any alterations on the methylation pattern of HAND2 gene in our sample. Moreover, alteration of the binding site of MeCP2, a nuclear protein involved in DNA methylation, was predicted along with alteration in HAND2 mRNA structure. CONCLUSIONS: Considering HAND2 being a well conserved gene, further studies with a larger sample should be performed to evaluate the role this gene on genetic susceptibility to TE.


Assuntos
Anormalidades Múltiplas , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Doenças Fetais , Cardiopatias Congênitas , Talidomida , Feminino , Humanos , Gravidez , Anormalidades Múltiplas/induzido quimicamente , Anormalidades Múltiplas/genética , Doenças Fetais/induzido quimicamente , Doenças Fetais/genética , Predisposição Genética para Doença , Cardiopatias Congênitas/induzido quimicamente , Cardiopatias Congênitas/genética , Talidomida/toxicidade , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
8.
Front Pharmacol ; 13: 841826, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35444550

RESUMO

Atrazine and Diuron are widely used herbicides. The use of pesticides contaminates the aquatic environment, threatening biodiversity and non-target organisms such as fish. In this study, we investigated the effects of acute exposure for 96 h hours to atrazine and diuron commercial formulations in zebrafish (Danio rerio, wild-type AB) embryos and larvae and adult stages. We observed a significant concentration-dependent survival decrease and hatching delays in animals exposed to both herbicides and in the frequency of malformations compared to the control groups. Morphological defects included cardiac edema, tail reduction, and head malformation. At 7 days post-fertilization (dpf), atrazine exposure resulted in a reduction in the head length at 2, 2.5, and 5 mg/L and increased the ocular distance at 1, 2, 2.5, and 5 mg/L atrazine when compared to controls. At the same age, diuron increased the ocular distance in animals exposed to diuron (1.0 and 1.5 mg/L) and no effects were observed on the head length. We also evaluated a behavioral repertoire in larvae at 7 dpf, and there were no significant differences in distance traveled, mean speed, time in movement, and thigmotaxis for atrazine and diuron when animals were individually placed in a new environment. The cognitive ability of the larvae was tested at 7 dpf for avoidance and optomotor responses, and neither atrazine nor diuron had significant impacts when treated groups were compared to their corresponding controls. Adults' behavior was evaluated 7 and 8 days after the end of the acute herbicide exposure. Exploration of a new environment and associated anxiety-like parameters, social interaction, and aggressiveness were not altered. Our results highlight the need for further studies on the sublethal effects of both herbicides and the consideration of the effects of commercial formulas vs. isolated active ingredients. It also emphasizes the need to take sublethal effects into consideration when establishing the environmental limits of residues.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34990834

RESUMO

Phenytoin (PHE) is an antiepileptic drug that has been widely used in clinical practice for about 80 years. It is mainly used in the treatment of tonic-clonic and partial seizures. The widespread consumption of this drug around the world has led to PHE being introduced into water bodies through municipal, hospital, and industrial effluent discharges. Since the toxic effects of this drug on aquatic species has been scarcely explored, the aim of this work was to investigate the influence of low (25-400 ngL-1) and high (500-1500 ngL-1) environmentally relevant concentrations of PHE on the development and oxidative status of zebrafish (Danio rerio) embryos. The toxicity of PHE was evaluated from 12 to 96 h after fertilization in D. rerio at concentrations between 25 and 1500 ngL-1. In both the control group and the 0.05% DMSO system, no malformations were observed, all embryos developed normally after 96 h. The severity and frequency of malformations increased with increasing PHE concentration compared to embryos in the control group. Malformations observed included developmental delay, hypopigmentation, miscellaneous (more than one malformation in the same embryo), modified chorda structure, tail malformation, and yolk deformation. Concerning the biomarkers of oxidative stress, an increase in the degree of lipid peroxidation, protein carbonylation, and hydroperoxide content was observed (p < 0.05) concerning the control. In addition, a significant increase (p < 0.05) in antioxidant enzymes (SOD, CAT, and GPx) was observed at low exposure concentrations (25-400 ngL-1), with a decrease in enzyme activity at high concentrations (500-1500 ngL-1). Our IBR analysis demonstrated that oxidative damage biomarkers got more influence at 500ngL-1 of PHE. The results demonstrated that PHE may affect the embryonic development of zebrafish and that oxidative stress may be involved in the generation of this embryotoxic process.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenitoína/toxicidade , Peixe-Zebra/embriologia , Animais , Antioxidantes/metabolismo , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário/efeitos dos fármacos , Enzimas/metabolismo , Testes de Toxicidade Aguda , Poluentes Químicos da Água/toxicidade , Proteínas de Peixe-Zebra/metabolismo
10.
Sci Total Environ ; 806(Pt 2): 150541, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34601175

RESUMO

Even though the toxic effects of paracetamol (PCM) and ciprofloxacin (CPX) have been deeply studied in the last decades, the impact of the PCM-CPX mixture may induce in aquatic organisms is poorly known. Thus, the objective of this work was to investigate the teratogenic effects and oxidative stress that PCM, CPX, and their mixture induce in Danio rerio embryos. Moreover, we aimed to determine whether the PCM-CPX mixture induces more severe effects on the embryos than the individual drugs. For this purpose, zebrafish embryos (4 hpf) were exposed to environmentally relevant concentrations of PCM, CPX, and their mixture until 96 hpf. In addition, at 72 hpf and 96 hpf, we also evaluated the oxidative stress biomarkers (superoxide dismutase, catalase, glutathione peroxidase, lipid peroxidation, and hydroperoxides and carbonyl content) in the embryos. Our results demonstrated that PCM, CPX, and their mixture reduced the survival rate of embryos by up to 75%. In addition, both drugs, induced morphological alterations in the embryos, causing their death. The most observed malformations were: scoliosis, craniofacial malformations, hypopigmentation, growth retardation, pericardial edema. Concerning oxidative stress, our integrated biomarkers response (IBR) analysis demonstrated that PCM, CPX, and their mixture induce oxidative damage on the embryos. In conclusion, PCM, CPX, and their mixture can alter zebrafish embryonic development via an oxidative stress response.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Acetaminofen/metabolismo , Acetaminofen/toxicidade , Animais , Ciprofloxacina/metabolismo , Ciprofloxacina/toxicidade , Embrião não Mamífero/metabolismo , Estresse Oxidativo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade
11.
J Matern Fetal Neonatal Med ; 35(25): 8723-8727, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34749588

RESUMO

Infections are frequent during pregnancy and their teratogenic role is well documented in Toxoplasmosis, other infections, Rubella, Cytomegalovirus, and Herpes simplex (TORCH). However, the in-utero development effects of the rest of the infections that affect pregnant women are unknown. We described a cohort of patients with major Birth Defects (BD) and the exposure to infections during pregnancy from the information of Congenital Defects Surveillance Programs of two Colombian cities (Bogota and Cali) between 2001 and 2018. We evaluated associations between groups of maternal infections and BD among 3096 cases and 7446 controls that were registered. BD presentation was more frequent as isolated (64.3%), polymalformed (23.2%), and syndromic (12.4%). Infections during pregnancy were present in 52.5% of cases and 44.6% of controls. The most common single infection between cases and controls was vaginal infection. The most common polyinfection was vaginal and urinary tract infection. We found an association between BD and vaginal infections with an odds ratio (OR) 1.18 (CI 1.08-1.30), urinary tract infections OR 1.16 (CI 1.05-1.28), gastrointestinal infections OR 2.06 (IC 1.18-3.59), respiratory infections OR 1.56 (IC 1.28-1.9) and viral infections OR 1.88 (IC 1.18-3.0). Knowing the teratogenic effect of infections is important to extend prevention, screening, timely diagnosis, and appropriate treatment to pregnant women.


Assuntos
Complicações Infecciosas na Gravidez , Rubéola (Sarampo Alemão) , Toxoplasmose , Humanos , Feminino , Gravidez , Colômbia/epidemiologia , Estudos de Casos e Controles , Rubéola (Sarampo Alemão)/complicações , Complicações Infecciosas na Gravidez/diagnóstico
12.
Biomedica ; 41(3): 493-503, 2021 09 22.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34559496

RESUMO

Introduction: Currently, diabetes mellitus represents one of the medical conditions that more frequently complicates pregnancy affecting the fetus's growth and development. Objective: To determine the skeletal malformations and growth alterations in fetuses of diabetic Wistar rats. Materials and methods: We used a neonatally streptozotocin-induced mild diabetes model (STZ 100 mg/kg body weight - subcutaneously) in Wistar rats. In adulthood, healthy and diabetic rats were mated with healthy males of the same age and strain. On day 20 of gestation, a cesarean was performed under anesthesia. Fetuses were removed, weighed, and classified as small (SPA), adequate (APA), and large (LPA) for the gestational age. Selected fetuses were processed for skeletal anomaly and ossification sites analysis. Results: In the offspring of diabetic rats, there was a higher percentage of fetuses classified as small or large and a lower percentage of fetuses with adequate weight; the fetal weight mean was lower and there were fewer sites of ossification. Alterations were observed in the ossification of the skull, sternum, spine, ribs and fore and hind limbs; and also, there was a direct correlation between fetal weight and ossification degree. There were congenital malformations associated with fusion and bifurcation of the ribs, as well as changes indicative of hydrocephaly, such as the dome shape of the skull, a wide distance between parietals, and the width of the anterior and posterior fontanels. Conclusion: Moderate diabetes during pregnancy alters fetal growth and development with macrosomia and intrauterine growth restriction, as well as skeletal malformations.


Introducción. En la actualidad, la diabetes mellitus representa una de las condiciones médicas que complica el embarazo con mayor frecuencia, lo que afecta el crecimiento y el desarrollo fetal. Objetivo. Determinar las malformaciones esqueléticas y alteraciones en el crecimiento en fetos de ratas Wistar diabéticas. Materiales y métodos. Se utilizó un modelo de diabetes moderada inducida neonatalmente con estreptozotocina (STZ 100 mg/kg de peso corporal, por vía subcutánea) en ratas Wistar. En la adultez, las ratas sanas y diabéticas se aparearon con machos sanos de la misma edad y cepa. El día 20 de gestación se practicó la cesárea bajo anestesia. Se extrajeron los fetos, se pesaron y clasificaron como pequeños (PAG), adecuados (AEG) o grandes (GEG) para la edad gestacional. Los fetos seleccionados se procesaron para el análisis de anomalías esqueléticas y sitios de osificación. Resultados. En la descendencia de las ratas diabéticas, hubo un mayor porcentaje de fetos clasificados como pequeños o grandes y un menor porcentaje de fetos con peso adecuado; el promedio de peso fetal fue menor y había menos sitios de osificación. Se observaron alteraciones en la osificación de cráneo, esternón, columna vertebral, costillas y extremidades anteriores y posteriores; y también, hubo una correlación directa entre el peso y el grado de osificación fetal. Hubo malformaciones congénitas asociadas con la fusión y bifurcación de las costillas, así como cambios indicativos de hidrocefalia, como la forma de domo del cráneo, una amplia distancia entre los parietales y la anchura de las fontanelas anterior y posterior. Conclusión. La diabetes moderada durante la gestación altera el crecimiento y el desarrollo fetal, que se ve afectado tanto por macrosomía y la restricción del crecimiento intrauterino como por malformaciones esqueléticas.


Assuntos
Diabetes Mellitus Experimental , Animais , Feminino , Retardo do Crescimento Fetal , Feto , Idade Gestacional , Masculino , Gravidez , Ratos , Ratos Wistar
13.
Biomédica (Bogotá) ; Biomédica (Bogotá);41(3): 493-503, jul.-set. 2021. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1345399

RESUMO

Resumen Introducción. En la actualidad, la diabetes mellitus representa una de las condiciones médicas que complica el embarazo con mayor frecuencia, lo que afecta el crecimiento y el desarrollo fetal. Objetivo. Determinar las malformaciones esqueléticas y alteraciones en el crecimiento en fetos de ratas Wistar diabéticas. Materiales y métodos. Se utilizó un modelo de diabetes moderada inducida neonatalmente con estreptozotocina (STZ 100 mg/kg de peso corporal, por vía subcutánea) en ratas Wistar. En la adultez, las ratas sanas y diabéticas se aparearon con machos sanos de la misma edad y cepa. El día 20 de gestación se practicó la cesárea bajo anestesia. Se extrajeron los fetos, se pesaron y clasificaron como pequeños (PAG), adecuados (AEG) o grandes (GEG) para la edad gestacional. Los fetos seleccionados se procesaron para el análisis de anomalías esqueléticas y sitios de osificación. Resultados. En la descendencia de las ratas diabéticas, hubo un mayor porcentaje de fetos clasificados como pequeños o grandes y un menor porcentaje de fetos con peso adecuado; el promedio de peso fetal fue menor y había menos sitios de osificación. Se observaron alteraciones en la osificación de cráneo, esternón, columna vertebral, costillas y extremidades anteriores y posteriores; y también, hubo una correlación directa entre el peso y el grado de osificación fetal. Hubo malformaciones congénitas asociadas con la fusión y bifurcación de las costillas, así como cambios indicativos de hidrocefalia, como la forma de domo del cráneo, una amplia distancia entre los parietales y la anchura de las fontanelas anterior y posterior. Conclusión. La diabetes moderada durante la gestación altera el crecimiento y el desarrollo fetal, que se ve afectado tanto por macrosomía y la restricción del crecimiento intrauterino como por malformaciones esqueléticas.


Abstract Introduction: Currently, diabetes mellitus represents one of the medical conditions that more frequently complicates pregnancy affecting the fetus's growth and development. Objective: To determine the skeletal malformations and growth alterations in fetuses of diabetic Wistar rats. Materials and methods: We used a neonatally streptozotocin-induced mild diabetes model (STZ 100 mg/kg body weight - subcutaneously) in Wistar rats. In adulthood, healthy and diabetic rats were mated with healthy males of the same age and strain. On day 20 of gestation, a cesarean was performed under anesthesia. Fetuses were removed, weighed, and classified as small (SPA), adequate (APA), and large (LPA) for the gestational age. Selected fetuses were processed for skeletal anomaly and ossification sites analysis. Results: In the offspring of diabetic rats, there was a higher percentage of fetuses classified as small or large and a lower percentage of fetuses with adequate weight; the fetal weight mean was lower and there were fewer sites of ossification. Alterations were observed in the ossification of the skull, sternum, spine, ribs and fore and hind limbs; and also, there was a direct correlation between fetal weight and ossification degree There were congenital malformations associated with fusion and bifurcation of the ribs, as well as changes indicative of hydrocephaly, such as the dome shape of the skull, a wide distance between parietals, and the width of the anterior and posterior fontanels. Conclusion: Moderate diabetes during pregnancy alters fetal growth and development with macrosomia and intrauterine growth restriction, as well as skeletal malformations.


Assuntos
Diabetes Mellitus Experimental , Retardo do Crescimento Fetal , Anormalidades Congênitas , Macrossomia Fetal , Teratogênese
15.
Front Genet ; 12: 680217, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249098

RESUMO

The identification of thalidomide-Cereblon-induced SALL4 degradation has brought new understanding for thalidomide embryopathy (TE) differences across species. Some questions, however, regarding species variability, still remain. The aim of this study was to detect sequence divergences between species, affected or not by TE, and to evaluate the regulated gene co-expression in a murine model. Here, we performed a comparative analysis of proteins experimentally established as affected by thalidomide exposure, evaluating 14 species. The comparative analysis, regarding synteny, neighborhood, and protein conservation, was performed in 42 selected genes. Differential co-expression analysis was performed, using a publicly available assay, GSE61306, which evaluated mouse embryonic stem cells (mESC) exposed to thalidomide. The comparative analyses evidenced 20 genes in the upstream neighborhood of NOS3, which are different between the species who develop, or not, the classic TE phenotype. Considering protein sequence alignments, RECQL4, SALL4, CDH5, KDR, and NOS2 proteins had the biggest number of variants reported in unaffected species. In co-expression analysis, Crbn was a gene identified as a driver of the co-expression of other genes implicated in genetic, non-teratogenic, limb reduction defects (LRD), such as Tbx5, Esco2, Recql4, and Sall4; Crbn and Sall4 were shown to have a moderate co-expression correlation, which is affected after thalidomide exposure. Hence, even though the classic TE phenotype is not identified in mice, a deregulatory Crbn-induced mechanism is suggested in this animal. Functional studies are necessary, especially evaluating the genes responsible for LRD syndromes and their interaction with thalidomide-Cereblon.

16.
Chemosphere ; 285: 131213, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34246938

RESUMO

In recent years, the consumption of metformin has increased not only due to the higher prevalence of type 2 diabetes, but also due to their usage for other indications such as cancer and polycystic ovary syndrome. Consequently, metformin is currently among the highest drug by weight released into the aquatic environments. Since the toxic effects of this drug on aquatic species has been scarcely explored, the aim of this work was to investigate the influence of metformin on the development and redox balance of zebrafish (Danio rerio) embryos. For this purpose, zebrafish embryos (4 hpf) were exposed to 1, 10, 20, 30, 40, 50, 75 and 100 µg/L metformin until 96 hpf. Metformin significantly accelerated the hatching process in all exposure groups. Moreover, this drug induced several morphological alterations on the embryos, affecting their integrity and consequently leading to their death. The most frequent malformations found on the embryos included malformation of tail, scoliosis, pericardial edema and yolk deformation. Regarding oxidative balance, metformin significantly induced the activity of antioxidant enzymes and the levels of oxidative damage biomarkers. However, our IBR analisis demonstrated that oxidative damage biomarkers got more influence over the embryos. Together these results demonstrated that metformin may affect the embryonic development of zebrafish and that oxidative stress may be involved in the generation of this embryotoxic process.


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Animais , Diabetes Mellitus Tipo 2/metabolismo , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário , Feminino , Hipoglicemiantes/toxicidade , Metformina/metabolismo , Metformina/toxicidade , Estresse Oxidativo , Peixe-Zebra
17.
Horiz. med. (Impresa) ; 21(2)abr. 2021.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1506308

RESUMO

El objetivo de este trabajo fue conocer la frecuencia y la manera en que las plantas medicinales son empleadas por las gestantes del Centro de Salud Viña Alta del distrito de La Molina. En el estudio participaron veintiuna gestantes, quienes respondieron una encuesta, validada por expertos, sobre el uso de plantas medicinales. Se demostró que el 86,00 % de las gestantes utilizaron plantas medicinales, y que 67,00 % no consultó con un médico sobre su empleo. La manera más frecuente de consumo de las plantas medicinales fue la vía oral, en forma de infusiones. Las plantas medicinales más utilizadas fueron manzanilla, perejil, eucalipto, boldo, aloe, menta y ruda; y algunas de ellas mostraron efecto teratogénico, estimulante uterino, abortivo, entre otros. Es necesario conocer la cantidad real y la manera más frecuente en que las gestantes consumen las plantas medicinales, con la finalidad de clasificar estos productos de acuerdo al nivel de seguridad que ofrecen y promover el uso racional de la medicina tradicional para contribuir en la salud pública.


This research aimed to find out the frequency and ways of using medicinal plants by pregnant women treated at the Centro de Salud Viña Alta, located in La Molina district. Twenty-one (21) pregnant women voluntarily participated in the study, where they were administered an expert-validated survey regarding the use of medicinal plants. The results showed that 86 % of the pregnant women used medicinal plants and 67 % did not ask their doctor before using them. The most frequent way of using the medicinal plants was by oral intake as herbal teas. The most widely used medicinal plants were chamomile, parsley, eucalyptus, boldo, aloe, mint and rue, some of which produced a teratogenic effect, uterine stimulant action, abortifacient effect, among others. It is necessary to know the actual quantity and most frequent way of using medicinal plants by pregnant women to classify these products as for its safety level and promote the rational use of traditional medicine to contribute to public health.

18.
Birth Defects Res ; 113(12): 981-994, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33750035

RESUMO

BACKGROUND: The deleterious effects of diabetes mellitus (DM) over development are apparently due to an increase in oxidative stress. Some antioxidants could prevent developmental alterations produced by diabetic state. Extracts of plants of the genus Buddleja are used traditionally for Mexican indigens to ameliorate some diseases. The purpose of this work was to evaluate the effect of the extract of Buddleja cordata over diabetic embryopathy. METHODS: Two experimental approaches were used: an in vivo study and an in vitro model. In the first, rats were treated with streptozotocin, streptozotocin plus methanolic extract of B. cordata, or none. Females were sacrificed at gestational day (GD) 19, and biochemical clinical parameters were measured; also, the fetuses were obtained and morphologically analyzed. In the in vitro model, a verbascoside-enriched fraction (VEF) of the extract was used in whole embryo culture in order to search for the mechanisms for embryoprotection effect over hyperglycemia-induced malformations. RESULTS: In the in vivo experiments, B. cordata extract reduces the frequency and severity of fetal malformations produced by chemically induced diabetes, and additionally partially ameliorates the diabetic condition; in the in vitro model, both severity and frequency of embryo dysmorphogenesis were reduced by the VEF; also, this fraction reduces lipoperoxidation without affecting the activity of the antioxidant enzymes. CONCLUSION: The results suggest that verbascoside of methanolic extract and enriched fraction can directly affect the redox state, and thus, prevents the embryotoxicity mediated by oxidative stress, in embryos of diabetic pregnancy.


Assuntos
Buddleja , Diabetes Mellitus , Doenças Fetais , Animais , Modelos Animais de Doenças , Glucosídeos , Fenóis , Gravidez , Ratos
19.
Sci Total Environ ; 768: 144585, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33454465

RESUMO

Paracetamol (PCM) is among the most consumed analgesic and antipyretic drugs worldwide. Due to its high consumption, this drug has been reported ubiquitously on different water bodies, posing a real threat to aquatic organisms. Until now, several studies have pointed out that PCM may induce oxidative stress, histological damage and developmental disorders on different aquatic species. Nonetheless, there is still a huge knowledge gap about the toxic effects that PCM may induce in species of commercial interest such as the common carp Cyprinus carpio. The aim of this study was to evaluate survival and malformation rates induced by PCM (0.5 µg/L - 3.5 µg/L) in early life stages of common carp. Furthermore, oxidative stress biomarkers were evaluated at 72 and 96 h post fecundation. PCM reduced the survival rate of the embryos of up to 90%, as concentration increased. LC50 and EC50m were 1.29 µg/L and 2.84 µg/L, respectively. Biomarkers of cellular oxidation and antioxidant enzymes were modified in a concentration-dependent way with respect to the control group (p < 0.05). The main developmental alterations observed were lordosis, scoliosis, craniofacial malformations, hypopigmentation, growth retardation, pericardial edema and rachyschisis. These data indicate that environmentally realistic concentrations of PCM could be hazardous and affects the development in early stages of C. carpio. Moreover, our findings also indicate that C. carpio embryos may be a useful in vivo model to evaluate embryonic and teratogenic effects of drugs such as PCM.


Assuntos
Carpas , Poluentes Químicos da Água , Acetaminofen/toxicidade , Animais , Antioxidantes , Oxirredução , Estresse Oxidativo , Poluentes Químicos da Água/toxicidade
20.
J Environ Sci Health B ; 56(1): 41-53, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33112724

RESUMO

Dexamethasone (DEX) is a glucocorticoid highly effective as an anti-inflammatory, immunosuppressant and decongestant drug. In the present study, a preliminary acute toxicity test was assayed in order to determinate DEX median-lethal, lowest-observed-effect and the no-observed-effect concentrations (LC50, LOEC and NOEC, respectively) on the common toad embryos (Rhinella arenarum). Also, morphological and histological abnormalities from five body larval regions, liver melanomacrophages (MM) and glutathione S-transferase (GST) activity were evaluated in the toad larvae to characterize the chronic sublethal effects of DEX (1-1,000 µg L-L). Results of the acute test showed that the LC50 of DEX at 96 h of exposure for the toad embryos (GS 18-20) was 10.720 mg L-g, and the LOEC was 1 µg L-g. In the chronic assay, the larval development and body length were significantly affected. DEX exposition also induced teratogenic effects. Most frequent external abnormalities observed in DEX-treated larvae included abdominal edema and swollen body, abnormal gut coiling and visceral congestion. Intestinal dysplasia was recurrent in cross-section of all DEX-treated larvae. Neural, conjunctive and renal epithelial cells were also affected. Significant increase in liver MM number and size, and GST activity levels were also registered in DEX treatments with respect to controls. The evaluation of a variety of biomarkers provided clear evidence of toad larvae sensitivity to DEX, and the ecotoxicological risk of these pharmaceuticals, commonly found in different water bodies worldwide on aquatic animals.


Assuntos
Anormalidades Induzidas por Medicamentos/veterinária , Bufo arenarum/crescimento & desenvolvimento , Dexametasona/toxicidade , Glucocorticoides/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Ecotoxicologia , Embrião não Mamífero/anormalidades , Embrião não Mamífero/efeitos dos fármacos , Larva/efeitos dos fármacos , Dose Letal Mediana
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