Embryotoxic and teratogenic effects of polyethylene microbeads using the zebrafish Danio rerio (Hamilton, 1822)

Background@#The escape of polyethylene microbeads from waste-water treatment facilities to aquatic habitats has been a major concern by scientific communities due to the adverse effects on aquatic organisms as well as the well-being of the marine and terrestrial ecosystems. @*Objective@#This study was conducted to evaluate the embryotoxic and teratogenic effects of polyethylene microbeads on the early development of the zebrafish Danio rerio using the Fish Embryo Acute Toxicity Test (FET). @*Methodology@#Sixty (60) zebrafish embryos were exposed to polyethylene microbead suspensions (PE-MBS) of 20 μg/L, 200 μg/L, and 2000 μg/L concentrations. Using FET, the toxicological endpoints (i.e., egg coagulation, lack of somite formation, non-detachment of tail, and lack of heartbeat) were observed every 24 hours until the 96th-hour exposure. Hatching of the embryo from the chorion was observed from 48-96 hpf (hours-post fertilization), and at least four parameters of teratogenicity (i.e., edema of the pericardium and yolk sac, bent axis, tail curvature, and collapsed swim bladder) was observed at 144 hpf. @*Results@#Significant differences between means and variances in the embryotoxic and teratogenic effects were observed for all treatment groups in relation to the negative control (reconstituted water). The emulsifier control (0.01% Tween 80, p-value=0.9), the solvent control (1% DMSO, p-value = 0.9), and the 20 μg/L PE-MBS (p-value = 0.92) did not significantly differ with the negative control group. However, the positive control (5% ethanol, pvalue= 7.8) and 200 μg/L (p-value = 1.1), and 2000 μg/L (p-value = 1.48) of PE-MBS were significantly embryotoxic and teratogenic to the developing organism. @*Conclusion@#The high concentrations of PE-MBS (200 μg/L and 2000 μg/L) may induce early hatching, mortality, and malformations. Tukey Kramer post hoc test substantiated that PE-MBS toxicity is dose-dependent since embryotoxicity and teratogenicity increase at higher concentrations. Further studies should be conducted to know more about the adverse effects of polyethylene microbeads on the development, physiology, and genomics of freshwater fishes.

Knowledge about Teratogenic Drugs among Dentists - A Cross-Sectional Survey

Teratogen is any agent that might interfere with the proper growth and development of the embryo or foetus. Teratogens usually involve radiation, cancer, chemicals, and drugs. Comprehension of teratogenic drugs is of great value to dental practitioners because they handle a wide range of drugs that cause teratogenicity in the care of patients with dental problems during pregnancy. The aim of this survey is to assess the awareness among dentists of teratogenic drugs. The study was conducted among 100 final year dental students and interns in Chennai City. 10 questions eliciting information on the knowledge and understanding of teratogenic drugs were framed and distributed. The responses obtained from the participants were compiled, processed further, and analyzed. 83% of the participants were aware of teratogenic drugs. This study concluded that knowledge about teratogenic drugs is adequate among dental students

Safety Profile and Toxicity Amelioration Strategies of Common Adverse Effects Associated with Anticancer Medications

More than half the cancer patients undergoing cancer chemotherapy develop adverse drug reactions (ADRs). Cancer chemotherapeutic agents have a lower risk-benefit ratio than other drug therapy and kill cancerous as well as the normal rapidly dividing cells including bone marrow cells, gastrointestinal epithelium, hair follicles, etc. Their main ADRs are nausea and vomiting, mucositis, constipation, diarrhea, hematological toxicities, cardiac toxicity, alopecia, gonadal toxicity pulmonary toxicity, neurotoxicity, nephrotoxicity, etc. The severity of the adverse effects may range from mild nausea to life-threatening neutropenia. Administering premedication and antidotes are very vital in these patients. Upon the occurrence of adverse effects, immediate steps should be taken to manage them. Though the ADRs due to anticancer medications are not avoidable, careful monitoring of the patients and modulating the drug schedules/dosages can help in minimizing them. Healthcare professionals should also develop strategies to minimize the occupational hazards associated with these drugs

Avaliação da toxicidade pré-natal: estudo de teratogenicidade do inseticida piriproxifeno em ratos Wistar / Prenatal toxicity assessment: teratogenicity study of the insecticide pyriproxyfen in Wistar rats

Este estudo investigou a toxicidade pré-natal do inseticida piriproxifeno em ratos Wistar, de forma a detectar possíveis alterações no desenvolvimento fetal da progênie exposta durante o período organogênico. Três doses de piriproxifeno (100, 300 e 500mg.kg-1) foram administradas por via oral às progenitoras, do sexto ao 15º dia de gestação. Os fetos foram submetidos à técnica de diafanização modificada descrita por Taylor e Van Dyke, para avaliação de malformações e alterações esqueléticas. Os resultados não demonstraram a ocorrência de toxicidade materna sistêmica ou alterações nos índices reprodutivos avaliados. Malformações ou alterações teratogênicas não foram detectadas, no entanto alterações esqueléticas sugestivas de retardo no desenvolvimento foram observadas especialmente nas doses mais altas testadas (300mg.kg-1 e 500mg.kg-1). Considerando-se a situação complexa de risco para a saúde humana, mostra-se importante a execução de investigações adicionais, de modo a contribuir para a adequada avaliação de risco do piriproxifeno em água potável.(AU)

This study investigated the prenatal toxicity of the insecticide pyriproxyfen in Wistar rats to detect the possible changes in the fetal development of the progeny exposed during the organogenic period. Three doses of pyriproxyfen (100, 300, and 500mg.kg-1) were administered orally to the progenitors, from day 6 to 15 of gestation. The fetuses were processed using the Taylor and Van Dyke modified diaphanization technique to evaluate malformations and skeletal changes. The results did not demonstrate the occurrence of systemic maternal toxicity or changes in the reproductive indexes evaluated. Malformations or teratogenic changes were not detected, however, skeletal changes suggestive of developmental delay were observed, especially in the highest doses tested (300 mg.kg-1 and 500 mg.kg-1). Owing to the potentially complex situation regarding its risk to human health, it is important that further studies be performed to contribute to the risk assessment of the addition of pyriproxyfen in drinking water.(AU)

Efeitos tóxicos dos sedimentos do estuário do rio Capibaribe em embriões de zebrafish (Danio rerio) / Toxic effects of sediments of the Capibaribe estuary on zebrafish embryos (Danio rerio)

O presente estudo utilizou embriões de Danio rerio expostos aos elutriatos dos sedimentos estuarinos do rio Capibaribe, dos períodos chuvoso e seco, e analisou os efeitos letais, teratogênicos, bem como a frequência cardíaca. Os testes de toxicidade com os embriões seguiram as diretrizes da OECD 236. Mediante os resultados obtidos, a frequência cardíaca e a teratogenicidade foram os efeitos mais observados nos animais quando submetidos às amostras. Entre os efeitos teratogênicos, o retardo geral no desenvolvimento dos embriões foi o mais frequente durante as análises. Tais efeitos tóxicos se modificaram entre os pontos e entre os períodos de coleta. Essa variação de toxicidade pode estar relacionada à diversidade de atividades realizadas no entorno desse estuário, a influência do regime de chuvas, marés e correntes, indicando que a análise dos efeitos subletais e da teratogenicidade em embriões de D. rerio constitui bom parâmetro para avaliações de toxicidade de amostras ambientais.(AU)

The present study used Danio rerio embryos exposed to the elutriates of the estuarine sediments of the Rio Capibaribe, from the rainy and dry periods, where the lethal effects, teratogenic and heart rate were analyzed. Embryotoxicity tests followed the guidelines of OECD 236. Based on the results obtained, heart rate and teratogenicity demonstrated higher sensitivity to the samples. Among the teratogenic effects, the general delay in embryo development was the most frequent effect during the analyzes. These toxic effects changed between the points and between the collection periods. This variation of toxicity may be related to the diversity of activities carried out around this estuary, the influence of rainfall, tides, and currents, indicating the analysis of sublethal effects and teratogenicity in the D. rerio embryos are useful parameters for toxic evaluation of environmental samples.(AU)

Pregnancy with chronic myeloid leukemia: case report and literature review

Chronic myeloid leukemia (CML) is a rare condition during reproductive age. Still, women may present with pre-existing or newly diagnosed CML during pregnancy. The management of chronic myeloid leukemia during pregnancy requires balancing the well-being of the mother with that of fetus. Tyrosine Kinase inhibitors are considered the most effective drug against CML but they are still not considered safe during pregnancy and breast feeding. So, there is a need for management of CML with alternate drugs during pregnancy. Here we report a case of a 26-year-old lady who was diagnosed with chronic myelogenous leukemia (CML) at 20 weeks of gestation and had an atypical chromosome translocation t (9:22). She was managed jointly by obstetrician and haemato-oncologist for the remainder of her pregnancy and eventually she delivered a healthy baby at term.

Teratogenicity study in rats of commonly used calcium channel blockers

Background: Calcium channel blockers (CCBs) are popular medicines used to treat hypertension, tachyarrhythmias or angina during pregnancy. Lack of adequate safety data has however created an uncertainty in the use of CCBs in pregnancy. Nifedipine has been reportedly associated with a variety of embryotoxic and fetotoxic effects in animals. Therefore, this study was undertaken to establish whether or not the commonly used CCBs (nifedipine and amlodipine) would produce teratogenic effects in rats.Methods: Twenty pregnant rats were randomly assigned to each of the treatment and control groups. Nifedipine and amlodipine were used in three dose levels of 5, 10, 20 mg/kg and 0.5, 1, 2 mg/kg body weight respectively to test its teratogenic effects. The maximum dose of the test drugs used in our study was ten times the maximum recommended human dose. The drugs were administered to the pregnant rats using nasogastric tubes from day 6 through day 15 of pregnancy. The number of live births, stillbirths, litter sizes, crown-rump lengths, birth weights and gross abnormalities of the pups delivered were observed and recorded. Skeletal changes and soft tissue changes were also observed in the pups delivered to treated pregnant rats.Results: It was found that nifedipine and amlodipine did not produce any teratogenic effects in rats at doses 2.5 to 10 times the recommended human dose. None of the pups showed any gross morphological, skeletal or visceral defects.Conclusions: Nifedipine and amlodipine appear to be safe during pregnancy in therapeutic doses.

Teratogenic and Mutagenic Toxicity of Agarwood Extracts Produced by Agar-Wit / 中国药学杂志

OBJECTIVE: To research the teratogenic and mutagenic toxicity of agarwood extracts produced by agar-wit technique for functional food development (slices dose 0.60 g•d-1). METHODS: Pregnant rats of 6 to 15 d were given with agarwood extracts at 45, 105, 150 mg•kg-1 by gastric perfusion directly every day, then killed and anatomized after being pregnant for 20 d. During the whole course of treatment, the activity and body weight of pregnant rats, fetal survival rate, absorption number, malformation type and number of fetus were observed and recorded. RESULTS: The agarwood extracts had no effect on the body weight of pregnant rats at 45, 105, 150 mg•kg-1 dosages, and the numbers of implantation, live fetuses, fetuses and stillbirths of fetus, malformation type and number had no significant difference compared with the control group (P>0.05). CONCLUSION: Agarwood extracts have no teratogenic and mutagenic toxicity for rat fetuses.

Impact of educational intervention on the awareness of undergraduate medical students towards teratogenicity: an observational study

Background: The term teratogenicity is defined as any morphological, behavioral or biochemical effect induced during embryonic life or fetal life detected at birth or later. the factors that lead to teratogenicity include both non-genetic and genetic factors. The objective of the present study was to assess the impact of educational interventions on the awareness of undergraduate medical students towards teratogenicityMethods: The present study was a questionnaire-based comparative observational study carried out at Department of Pharmacology and Therapeutics, Government Medical College, Jammu (J&K) for a period of three months from 1st November 2017 to 31st January 2018. The questionnaire was designed and validated by conducting pilot study on a sample of ten students. The questionnaire comprised of two main parts. The first part comprised of questions pertaining to the demographic profile of the students and second part consisted of questions assessing the students’ knowledge and awareness towards teratogenicity. The scoring of the assessment of the performance of the students regarding knowledge of various aspects of teratogenicity was done before and after the educational intervention and was compared using paired t-test.Results: A total of 134 second year MBBS undergraduate students participated in the study. Mean age of students was 19.32±0.82 years. In the present study it was found that before the educational intervention about 98.5% of the students and after the intervention all the students were aware of the term teratogenicity. About 69.4% of students knew about all the causes that lead to teratogenicity but after the intervention about 76.1% of the students knew about it. Also, the percentage of students who knew about the name of two teratogenic drugs and two teratogenic defects associated with drugs were only 31.3% and 22.3% respectively. After the educational intervention it increased to 61.9% and 52.2% respectively.Conclusions: In the present study, it was found that after the educational intervention, there was a significant improvement in the mean knowledge score of the students. This reflects the need of early exposure of students to this important issue of teratogenicity.

Catha edulis forsk mediates embryotoxic effects in rats: an experimental study / Catha edulis forsk modera los efectos embriotóxicos en ratas: un estudio experimental

Catha edulis Forsk leaves (Khat) is a flowering plant. A high proportion of the adult population in the Arabian Peninsula and the Horn of Africa chews it for its mild stimulant effect. The aim of the current study was to investigate the embryotoxic and teratogenic effects of the Khat extract using 60 female pregnant rats. These were divided to a Khat extract-treated group and a control group. Methanolic extract of Khat was orally given to the treated group 4 days before mating and up to day 16 of pregnancy with a dose of 100 mg/kg. Our results showed that significant number of embryos of the Khat-treated mothers were malformed and different in size and shape compared to embryos from the mothers of the control group. At day 8 of pregnancy, malformed embryos had ill developed primitive layers. By day 10 of pregnancy, neural tube and the somite were not formed compared to the control embryos. At later stages of pregnancy, embryos of the Khat-treated mothers appeared severely abnormal with opened neural groove and visceral pouches. Disrupted normal neural tube development, undifferentiated brain vesicles, incomplete closure of the brain flexures were also observed in these embryos. Highly significant increase in the number of the resorbed embryos of the Khat-treated mothers were observed (P < 0.01). The resorbed embryos appeared as a cellular collection in their placenta with some of their decidua had no visible embryonic tissues. In conclusions, Khat induced embryotoxic effects as well as severely affected the early normal embryonic development in rat.

Catha edulis (Khat) es una planta floreciente. Una alta proporción de la población adulta en la Península Arábiga y el Cuerno de África la mastica por su efecto estimulante. El objetivo del presente estudio fue investigar los efectos embriotóxicos y teratogénicos del extracto de Khat utilizando 60 ratas hembras preñadas. Estas se dividieron en un grupo tratado con extracto de Khat y un grupo control. El extracto metanólico de Khat se administró por vía oral al grupo tratado 4 días antes del apareamiento y hasta el día 16 de preñez con una dosis de 100 mg / kg. Los resultados mostraron que una cantidad significativa de embriones de las madres tratadas con Khat tenían malformaciones y eran diferentes en tamaño y forma en comparación con los embriones de las madres del grupo control. En el día 8 de preñez, los embriones malformados tenían capas primitivas mal desarrolladas. Para el día 10 de preñez, el tubo neural y el somito no se formaron en comparación con los embriones del grupo control. En etapas posteriores de la preñez, los embriones de las madres tratadas con Khat parecían severamente anormales con surcos neurales abiertos y bolsas viscerales. También se observaron alteraciones en el desarrollo normal del tubo neural, vesículas cerebrales indiferenciadas y el cierre incompleto de las flexiones cerebrales en estos embriones. Se observó un aumento altamente significativo en el número de embriones reabsorbidos de las madres tratadas con Khat (P <0,01). Los embriones reabsorbidos aparecieron como una colección celular en su placenta con algunas de sus deciduas sin tejidos embrionarios visibles. Khat indujo efectos embriotóxicos y afectó severamente el desarrollo embrionario normal temprano en la rata.

Morphological and skeletal abnormalities induced by α/β arteether on developing chick embryo

Introduction: Malaria continues to be one of the India's leading public health problem.α/β artether is one of the most common antimalarial drug used worldwide to treat chloroquine resistant malaria and malaria falciparum. The present study was designed to assess the teratogenic effects of α/β artether on developing chick embryo. Material and Methods: The study was performed on 300 fertilized eggs of white leg horn chicken.The eggs were divided in to five experimental groups A, B, C, D, E having 30 eggs each and five control groups a,b,c,d,e one each for every experimental group respectively having 30 eggs each. On 5th day of incubation eggs from experimental groups A, B, C, D and E were exposed to α/β artether with dose of 0.00039 mg, 0.000585 mg, 0.00078 mg, 0.00097 mg and 0.00117 mg whereas the control groups were treated with same amount of normal saline. Results: The results showed growth retardation and some significant morphological abnormalities like scanty feathers, subcutaneous hemorrhage and skeletal abnormalities like poor ossification of the bones, kyphosis and lordosis. Discussion: The drug is toxic specially when used in higher dose and for a long period. At present there is no alternative drug available for the treatment of chloroquine resistant malaria and malaria falciparum except α/β artether. Therefore α/β artether and other artemisinins should be used only after establishment of proper diagnosis in recommended dose only not in higher dose and not for a long duration.

Update on the safety of antithyroid drugs during pregnancy and lactation / 中华内分泌代谢杂志

Hyperthyroidism in pregnant and breastfeeding women should be adequately treated to prevent maternal and fetal complications. The choice of treatment during pregnancy and lactation is antithyroid drugs ( ATDs) . The risk of embryopathies in fetus and the effect on thyroid function of infants associated with the use of ATDs have been concerned for a long time. Large observational studies have quantified an increased risk of embryopathies associated with the use of methimazole ( MMI) and propylthiouracil ( PTU) during pregnancy, despite the effects of PTU appear less severe. Guidelines recommended PTU as the first-line choice for the first trimester during pregnant. And it is safe for ATDs use in lactating mothers. However, China Food and Drug Administration added the requirement of forbidden use of MMI during lactation this February. Accompanied by the updated guidelines for thyroid disease during pregnancy and the postpartum by American Thyroid Association, the issues of ATDs use during pregnancy as well as postpartum need to be further clarified.

Differences between NMRI and DBA/2J mice in the development of somites and susceptibility to methylnitrosourea-induced skeleton anomalies

ABSTRACT The development of DBA/2J mouse strain embryos is nearly 12 h - or 6 somite pairs - delayed as compared to the outbred NMRI mouse embryos of the same age on gestation days (GD) 8-12. To evaluate inter-strain differences in susceptibility to teratogens, dams were treated with methylnitrosourea (MNU, 5 mg/kg body weight i.p.) on defined gestation days (NMRI: GD 9, 91/2 or 10; DBA/2J: GD 10 or 101/2). Skeletal anomalies produced by MNU on both mouse strains varied with the GD of treatment. The pattern of anomalies produced by MNU on a given GD markedly differed between the two mouse strains, yet they were similar -with a few exceptions- when exposures at equivalent embryonic stages are compared. Findings from this study indicated that strain-dependent differences in the developmental stage of mouse embryos of the same gestational age occur, a possibility that has been often neglected when inter-strain differences in susceptibility to developmental toxicants are interpreted.

4．Evaluation of the Risk Minimization Plan of the Drugs such as Thalidomide / 薬剤疫学

If mother use drugs during pregnancy, the risk to the fetus is concerned. So the management of the drug is important. Previously, we have experienced The Thalidomide Disaster, the drug has not been used for many years since then. However, since thalidomide is found to have an effect on multiple myeloma, its management method is problematic. In the patients who use thalidomide, there are few women with the possibility of pregnancy. And by strict management, it has been concerned about the problem of the things that is difficult to use in patients not related to pregnancy. Isotretinoin is currently being used in the United States as the drug for acne therapy. Although there is no adaptation in Japan, the physician personally import the drug and administer to the patients. Because a lot of childbearing women are included in the patient who use the drug, strict management is necessary. Because the drug is not marketed in Japan, the offer of the information is not enough. Valproic acid has both adaptation the prevention of the migraine headache other than epilepsy. The control of epilepsy is very important, there are patients that use the drug after consideration of risk benefit balance. On the other hand, benefit was relatively small when use it for the prevention of the migraine headache. FDA prohibited the use during pregnancy for this purpose. In Japan, it is the same regulation regardless of adaptation, and balance of the risk benefit is not clear. It was thought that different attention awakening should be carried out by adaptation in future.

<b>4．Evaluation of the Risk Minimization Plan of the Drugs such as Thalidomide </b> / 薬剤疫学

<p>If mother use drugs during pregnancy, the risk to the fetus is concerned. So the management of the drug is important. Previously, we have experienced The Thalidomide Disaster, the drug has not been used for many years since then. However, since thalidomide is found to have an effect on multiple myeloma, its management method is problematic. In the patients who use thalidomide, there are few women with the possibility of pregnancy. And by strict management, it has been concerned about the problem of the things that is difficult to use in patients not related to pregnancy. Isotretinoin is currently being used in the United States as the drug for acne therapy. Although there is no adaptation in Japan, the physician personally import the drug and administer to the patients. Because a lot of childbearing women are included in the patient who use the drug, strict management is necessary. Because the drug is not marketed in Japan, the offer of the information is not enough. Valproic acid has both adaptation the prevention of the migraine headache other than epilepsy. The control of epilepsy is very important, there are patients that use the drug after consideration of risk benefit balance. On the other hand, benefit was relatively small when use it for the prevention of the migraine headache. FDA prohibited the use during pregnancy for this purpose. In Japan, it is the same regulation regardless of adaptation, and balance of the risk benefit is not clear. It was thought that different attention awakening should be carried out by adaptation in future.</p><p></p>

Development Toxicity of Ningmitai Capsules on Embryo and Fetus of Mice / 中国药师

Objective:To evaluate the matrix toxicity, embryo-fetal development toxicity and teratogenicity of Ningmitai capsules with oral administration in pregnant mice. Methods:After successful mating, the female mice were given Ningmitai capsules respec-tively at the dose of 5. 2, 10. 4 and 20. 7 g·kg-1 ·d-1 from the 6th to 15th day with gavage administration, and those in the control group were given saline. The body weight was recorded during the whole study. On the 18th day, the pregnant mice were dissected, and the number of corpora lutea, live fetus, dead fetus and absorptive fetus was recorded, respectively, and the appearance, body weight, skeleton and internal organs were observed. Results:No notable abnormality showed in the above indices in the pregnant mice and the embryo and fetus, and there were no statistically significant differences between Ningmitai capsules group and the control group. Con-clusion:Under the experimental conditions, Ningmitai capsules show no obvious toxicity on matrix, embryo and fetus of mice.

Developmental Toxicity and Potential Teratogenicity of Compound Danshen Tablet, Angong Niuhuang Pill, and Lidan Paishi Tablet in Zebrafish Embryos / 中草药·英文版

Objective Herbal medicines containing toxic herbs or minerals such as Compound Danshen Tablet (CDT), Angong Niuhuang Pill (ANP), and Lidan Paishi Tablet (LPT) are avoided or used with caution for pregnant women because of potential teratogenicity. To understand their mechanism, they were chosen as model subjects for the research. Methods Zebrafish embryos were used to evaluate their potential teratogenic risk in vitro. Results All of them showed teratogenic and lethal effects in zebrafish embryos, with the EC50 values at 351, 793, and 220 μg/mL, and LC50 values at 417, 596, and 380 μg/mL, respectively. CDT and LPT, displaying week potential teratogenicity as their teratogenicity indexes were greater than 1, induced tail malformation and cardiac edema mainly in zebrafish embryos, respectively. Conclusion The results provide the significant guidance of clinical safety of medication.

Maternal and fetal toxicity of Wistar rats exposed to herbicide metolachlor / Toxicidade materna e fetal de ratas Wistar expostas ao herbicida metolacloro

Metolachlor is a selective pre-emergent herbicide widely used in agriculture to control weeds. The aim of this study was to evaluate the possible effects of metolachlor on reproductive performance of adult rats, as well as its teratogenic potential when administered during the period of organogenesis. Pregnant adult female rats were allocated into 4 experimental groups (n = 10 group-1), that received 0 (control); 150 (TA); 300 (TB); or 1000 mg kg-1 bw day-1 (TC) of metolachlor, by gavage, from the 6th to 15th gestational day (GD). There is reduction in the weight gain of the animals from TB and TC groups compared to the control group. Liver and placenta weights were reduced in TB and TC groups, respectively, while the percentage of post-implantation loss was increased in the TC group. There were no external malformations in either rat of the control or treated groups. However, an increased incidence of skeletal anomalies and visceral anomalies (especially in the urogenital system) was observed in TC group. These results demonstrate that exposure of pregnant rats to metolachlor can lead to signs of general toxicity, late embryonic losses and congenital anomalies.

O metolacloro é um herbicida seletivo de pré-emergência, amplamente usado na agricultura para controlar ervas daninhas. O objetivo deste estudo foi avaliar os possíveis efeitos do metolacloro sobre o desempenho reprodutivo de ratas adultas, bem como o seu potencial teratogênico quando administrado durante o período da organogênese. Ratas adultas prenhes foram divididas em quatro grupos experimentais (n = 10 grupo-1), que receberam 0 (controle); 150 (TA); 300 (TB); ou 1.000 mg kg-1 dia-1 (TC) do metolacloro, via gavagem, do sexto ao 15º dia de gestação (DG). Foi observada redução no ganho de peso dos animais dos grupos TB e TC em comparação ao grupo controle. Os pesos do fígado e placenta foram reduzidos nos grupos TB e TC, respectivamente, enquanto que a percentagem de perda pós-implantação foi aumentada no grupo TC. Não foram observadas malformações externas nos ratos dos grupos controle e tratados. No entanto, foi observado aumento da incidência de anomalias esqueléticas e anomalias viscerais (especialmente no sistema urogenital) no grupo TC. Estes resultados demonstram que a exposição de ratas prenhes ao metolacloro pode levar a sinais de toxicidade geral, perdas embrionárias tardias e anomalias congênitas.

Caffeine teratogenicity in rats: morphological characterization and hypothesized mechanisms

Caffeine consumption during pregnancy has been shown in the scientific literature to be associated with teratogenicity such as low birth weight, fetal malformations, and miscarriage. However, the morphological alterations of the offspring of dams exposed during pregnancy have not been consistently described, and the mechanisms why they occur remain elusive. Thus, we aimed to characterize the offspring malformations induced by moderate and high doses of caffeine during pregnancy. Dams were divided into three groups: control, moderate (0.3 g/L), and high dose (1.0 g/L) of caffeine, which was provided in the drinking water beginning on gestational day 1 and continuing throughout the entire gestation. At moderate doses, only one of the dams had stillborn pups, although no macroscopic malformations were observed. High doses of caffeine induced significantly more malformations (P<0.001) and early death (before P4). The malformations observed were related to fetal development and cardiovascular alterations, namely bruises, macrocephaly with short limbs, abnormal development (or absence) of head structures and limbs, labial malformations, hydrops fetalis, and poor placental formation. We discussed the proposed mechanisms by which caffeine might induce these phenotypes, which may involve down-regulation of adenosine A1 receptors, and increased mothers' catecholamines. Our findings further confirm the evidence of the teratogenic effects of high doses of caffeine administered during pregnancy. These findings support the recommendation to avoid caffeine exposure during pregnancy (AU)

Post-natal development of rats` offspring treated with the ethanol extract of Neem leaves (Azadirachta indica A. Juss) during pregnancy and lactation / Desenvolvimento pós-natal de proles de ratas tratadas com o extrato etanólico das folhas de nim (Azadirachta indica A. Juss) durante a gestação e lactação

Teratogenicity and developmental abnormalities in the offspring of female rats that ingested ethanol extract of Neem plants during pregnancy and lactation period were assessed. Twenty-four female Wistar rats were randomly distributed in control group and in three experimental groups and treated during the 4th, 5th, and 6th day of pregnancy. After birth, the lactating females received, by gavage, 65, 135 and 200 mg kg-1 of Neem ethanol extract, during 15 days. Results show, there was no significant difference in body mass index of neonatal rats in the 4 groups evaluated, whereas mean rate of offspring survival was 79.4%. Hair growth, incisor teeth eruption, ear detachment, eyelid opening, and spontaneous ambulation were similar for all groups. Likewise, physical development and development of motor activity, ambulation, and postural reflexes were similar for all groups. The administration of Neem ethanol extract did not cause any reproductive or systemic toxicity in animals. Results show that, Neem ethanol extract safe at doses 65, 135 and 200 mg kg-1 in pregnant or lactating rats.

Teratogenicidade e anormalidades no desenvolvimento de proles de ratas que ingeriram o extrato etanólico de folhas de nim durante a gestação e lactação foram avaliadas. Vinte e quatro ratas Wistar foram distribuídas aleatoriamente em um grupo controle e três grupos experimentais tratados no quarto, quinto e sexto dias de gestação. Após o nascimento, as fêmeas lactantes receberam através de gavagem, o extrato etanólico de nim nas doses de 65, 135 e 200 mg kg-1 durante 15 dias. Nenhuma diferença significativa foi observada em relação ao índice de massa corpórea das fêmeas em lactação nos grupos em todos os momentos e a taxa média de sobrevivência dos filhotes foi de 79,4%. O tempo de crescimento piloso, erupção dos dentes incisivos, descolamento de orelha, abertura palpebral e deambulação espontânea foram semelhantes em todos os grupos. O desenvolvimento físico e da atividade motora, deambulação e reflexos posturais foram semelhantes em todos os grupos. A administração não resultou em toxicidade reprodutiva ou sistêmica. Os resultados mostraram que o extrato etanólico do nim é seguro para uso nas doses de 65, 135 e 200mg kg-1 em ratas prenhes ou em lactação.