• Title/Summary/Keyword: Teratogenic effect

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Teratogenicity of the Extracts of Crude Drugs (생약(生藥)의 최기성(崔畸性)에 관한 연구(硏究))

  • Lee, Eun-Bang
    • Korean Journal of Pharmacognosy
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    • v.13 no.3
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    • pp.116-121
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    • 1982
  • In order to investigate the side-effects of crude drugs, twenty drugs have been tested for the teratogenic effect in rats. Among seven drugs contained alkaloid as their ingredients, no one showed teratogenic effect, but Veratri rhizoma showed embryo-toxic as revealed by severe retardation in growth of the fetuses. The other thirteen drugs which have been used freguently in oriental medicines exhibited no teratogenic effect. Cyclophosphamide used as a reference compound showed severe malformation and retardation in the growth of rat fetuses. These findings suggest that the drug extracts adopted for the study might have no teratogenic effect in the rats.

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Teratogenic Effect of Carbamazepine (카바마제핀의 기형발생 효과)

  • Choi, Yeong-Tae;Cheon, Jin-Sook
    • Korean Journal of Biological Psychiatry
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    • v.5 no.2
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    • pp.283-287
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    • 1998
  • The mother was 24 years old, primipara, and had been taking carbamazepine 400mg(serum concentration $5.0-8.5{\mu}g/ml$) during pregnancy without any clinical seizures. A male baby with physical malformation was delivered on week 39. The malformation is extradigit(polydactily) on X-ray of right foot and left mild hydronephrosis on ultrasonography and renal scan with radioactive material. We reported this rare case and reviewed related articles about teratogenic effect of carbamazepine, mechanism of action and prevention of teratogenesis.

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Teratogenic Effects of Phenytoin on Rat Embryos in Culture (랫드에 있어서 배양배자에 대한 Phenytoin의 최기형성 효과)

  • Kim, Jong-Choon;Lim, Kwang-Hyeon;Chung, Moon-Koo;Roh, Jung-Koo
    • Toxicological Research
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    • v.14 no.3
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    • pp.357-363
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    • 1998
  • The teratogenic potential of the anticonvulsant drug phenytoin (PHT) has been well documented both in the human and in the experimental animals. However there are few reports on the effects of PHT on embryonic development in rats in vitro. The present study was performed to evaluate the teratogenic effects of PHT using whole-embryo culture system in rats. Sprague-Dawley rat embryos were explanted on gestational day (GD) 9.5 and cultured for 48 hrs in the immediately centrifuged and heat-inactivated rat serum containing 0,25,50, or $100{\mu}g$ PHT/mL. At the end of culture period the embryos were scored for morphological development according to the procedure of Van Maele-Fabry, and their total protein contents were determined. At 100 ${\mu}$g/mL of culture medium. PHT caused significant reduction in developmental score and protein content of embryos and a high incidence morphological abnormalities (100%). Characteristic malformations included altered yolk and embryonic circulation, craniofacial hypoplasia, neural tube schisis, branchial arch defects, abnormal ratation, and limb bud hypoplasia, among others. There were no adverse effects on embryonic growth and development at concentrations of 25 and 50 ${\mu}$g /mL of culture medium. The results indicated that the dysmorphogenic effect of PHT on cultured embryos is due to a direct interference with embryonic development.

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Toxicity Evaluation of Chemicals using Asian Toad Embryos, Bufo gargarizans (두꺼비 배아를 활용한 화학물질의 독성평가 연구)

  • Ko, Sun-kun
    • Korean Journal of Environment and Ecology
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    • v.30 no.4
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    • pp.705-711
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    • 2016
  • In this experiment, embryos of Asian toad, Bufo gargarizans, were investigated to evaluate toxicity of chemicals along FETAX(Frog Embryo Teratogenesis Assay-Xenopus) protocol. Asian toad, Bufo gargarizans, embryos incubated and investigation of Zn and Benomyl effect by probit analysis. As a result, depends on the concentrations of Zn and Benomyl, mortality and malformation rates were increases and larval body length were decreased. The teratogenic concentration($EC_{50}$) of Zn and Benomyl were 2.3, $1.0mg/{\ell}$, respectively and the embryo lethal concentration($LC_{50}$) Zn and Benomyl were 10.3, 6.9, respectively. The teratogenic index(TI) were 4.4 in Zn and 6.7 in Benomyl, thus showed teratogenicity in embryonic development of B. gargarizans. These results reveal that Zn and Benomyl in this experiment suppressed the development of embryos at relatively low concentration. Much of B. gargarizans embryos can be secured, and easy to incubate. In addition, mortality, malformation ratios, malformation patterns and growth rates are similar to the results from the other assay systems. Therefore, the B. gargarizans embryo teratogenesis assay system could be a useful tool to evaluate toxicity of pollutants in environment.

Toxic Effect of Cadmium on the Amphibian Axis Formation (카드뮴이 양서류의 체축 형성에 미치는 독성 효과)

  • 김윤경;정해문
    • Toxicological Research
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    • v.11 no.1
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    • pp.37-42
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    • 1995
  • Effect of cadmium on the early amphibian development was analyzed through FETAX (Frog Embryo Teratogenesis Assay: Xenopus). Embryos manifested concentration-dependent mortality and realformations; shortage of anterior-posterior axis gut realformation, ocular anomalies, bent notochord, misshapen dorsal fin, and derreal blisters. The treatment with 1.5ppm cadmium solution caused 100% mortality and concentration of lppm did not kill the embryos that caused 100% anomaly. The teratogenic index (TI = LC50 /EC50) was 2.8 indicating that $CdCl_2$ is teratogenic for Xenopus laevis. Embryos that were pulsetreated with at early to late blastula stage (St. 3-9) and mid to late blastula stage (St. 6-10) showed relatively strong resistance to cadmium, but the embryos treated at gastrula stage (St. 10-13) showed high mortality. And the embryos treated at tailbud stage (after St. 25) showed highest mortality of any other early stages. Effects of temperature were studied through pulse- treatment during gastrula stage at $20^{\circ}C$ and $30^{\circ}C$. The embryos treated with 7.5ppm at $30^{\circ}C$ and 15ppm at $20^{\circ}C$ caused 100% mortality respectively, indicating that higher temperature had more severe toxic effect. One of the most peculiar effect of cadmium at gastrulation was distortion of the tail. The probable cause of toxic effect of Cd was discussed.

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Teratogenicity of phenytoin in ICR mouse and antiteratogenic effect of dimethyl sulfoxide (ICR마우스에서 phenytoin의 최기형성 및 dimethyl sulfoxide의 항최기형 효과)

  • Lee, Jae-kwon;Lee, Chang-eop;Lee, Mun-han;Ryu, Pan-dong;Cho, Myung-haing;Sung, Ha-jung;Park, Jin-bong
    • Korean Journal of Veterinary Research
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    • v.34 no.4
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    • pp.821-831
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    • 1994
  • Phenytoin(PHT), a commonly prescribed anticonvulsant, has been known as a teratogen in experimental animals and human. However, PHT has strain-specific teratogenic effects for mice and human. Dimethyl sulfoxids(DMSO) has been known to antagonize the teratogenic effects of secalonic acid D, a toxic mold metabolite that has similar teratogenic effects to PHT. Therefore, this study was performed to examine the embryopathic effects of PHT in terms of treatment period and the antiteratogenic effect of DMSO in ICR mice. PHT(75mg/kg, BW) was administered intrapetitoneally on day 10, 10-11 and 10-12 of gestation with or without DMSO(2ml/kg, BW), and the fetal malformation was observed on day 18. Major malformation of fetuses treated with PHT on day 10, 10-11 and 10-12 of gestation was cleft palate, and the percentages of fetus with cleft palate were 14.5%, 31.7% and 51.7%, respectively. Also, there was a significant decrease of cleft palate from 51.7% in PHT alone group to 30.8% in PHT plus DMSO group. Our findings suggest that cleft palate is one of major malformation by PHT treatment in ICR mouse and DMSO has strong antiteratogenic effect.

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Effects of Pesticides(Benomyl, Carbofuran, Thiobencarb) on the Asian Toad(Bufo Gargarizans) Embryo Development (농약류(Benomyl, Carbofuran, Thiobencarb)가 두꺼비(Bufo Gargarizans) 배아발달에 미치는 영향)

  • Ko, Sun-Kun
    • Korean Journal of Environment and Ecology
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    • v.34 no.3
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    • pp.207-215
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    • 2020
  • In this experiment, investigated toxicity evaluation of chemicals using Asian toad embryos, along FETAX(Frog Embryo Teratogenesis Assay-Xenopus) protocol. Asian toad, Bufo gargarizans embryo incubated and investigation of Benomyl(Germicide), Carbofuran(Insecticide) and Thiobencarb(Herbicide) effect by probit analysis. As a result, depends on the concentrations of Benomyl, Carbofuran and Thiobencarb, along mortality and malformation rates were increases and larval body length were decreased. The teratogenic concentration(EC50) of Benomyl, Carbofuran and Thiobencarb were 1.03, 8.74, 4.98mg/ℓ, respectively. And when exposed to Benomyl, larvae responded most sensitively to malformations. Embryo lethal concentration (LC50) Benomyl, Carbofuran and Thiobencarb were 7.26, 560.72, 16.87mg/ℓ, respectively. And Benomyl were at the lowest concentration of lethal the embryos. The teratogenic index(TI) were 7.05 in Benomyl, 64.16 in Carbofuran and 3.39 in Thiobencarb, thus TI values were above 1.5, which is the criterion of teratogenicity. Three of the pesticides used in this study were considered to be a teratogenic substances and Carbofuran was the most potent teratogen. And more specific researches are needed to investigate the effects of pesticides on the embryo development of toads and amphibians and their mechanism.

Effects of fungicide tebuconazole on the embryonic development of Korean domestic frogs (Bufo gargarizans, Hyla japonica, and Pelophylax nigromaculatus) (살균제 Tebuconazole이 한국산 개구리류(두꺼비, 청개구리, 참개구리) 배아 발달에 미치는 영향)

  • Lee, Hae-Bum;Ko, Sun-Kun
    • Korean Journal of Environmental Biology
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    • v.39 no.3
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    • pp.311-318
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    • 2021
  • In this experiment, we investigated the toxicity of tebuconazole (fungicide) using domestic frog embryos, along the FETAX (Frog Embryo Teratogenesis Assay-Xenopus) protocol. Bufo gargarizans, Hyla japonica, and Pelophylax nigromaculatus embryos were incubated, and investigation of the tebuconazole effect was performed by the probit analysis. As a result, depending on the concentrations of tebuconazole, the mortality and malformation rates were increased and larval body length was decreased. The teratogenic concentrations (EC50) of tebuconazole were 34.4mg L-1, 10.6mg L-1, and 14.9mg L-1, respectively, and the embryo lethal concentrations(LC50) of tebuconazole were 74.7 mg L-1, 38.5 mg L-1, and 39.1 mg L-1, respectively. The teratogenic index (TI) valuesof tebuconazole were 2.19, 3.58, and 2.65; thus, it showed teratogenicity in embryonic development of these three frogs. These results revealed that in this experiment, tebuconazole suppressed the development of embryos at a relatively low concentration. In addition, mortality, malformation ratios, malformation patterns, and growth rates were similar to the results from the other assay systems. Therefore, tebuconazole was thought to have an effect on the embryo development of domestic frogs. In future, it will be necessary to identify species specificity in order to the clarify the causes of differences in mortality, malformation rate, and malformation patterns depending on the species.

Clinical Factors Affecting the Serum Retention of a Teratogenic Etretinate after the Acitretin Administration

  • Jeong, Jong Heon;Hyun, Gyu Hwan;Park, Yu Jeong;Kwon, Sung Won;Lee, Ai-Young
    • Biomolecules & Therapeutics
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    • v.30 no.6
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    • pp.562-569
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    • 2022
  • Etretinate, an acitretin metabolite, has a long retention duration in adipose tissues with a teratogenic potential. FDA advises a contraceptive period of at least three years after discontinuing acitretin. However, the effect of accumulated etretinate in adipose tissues on fetus is unknown. Although the teratogenic threshold for serum concentration of etretinate has been presented as higher than 2 ng/mL, that of acitretin is unknown. To examine factors affecting body retention of acitretin and etretinate, effects of acitretin dosage, acitretin-taking duration, elapsed time after stopping acitretin, age, sex, concomitant alcohol consumption, and foods and supplements rich in vitamin A intake on serum concentrations of acitretin and etretinate were analyzed in 14 acitretin-taken patients and 58 controls without taking acitretin or etretinate. Serum concentrations of acitretin, but not etretinate, tended to be inversely related to the discontinuation duration. They were also related to old age. Different from a published result that alcohol consumption could promote the metabolism of acitretin into etretinate, alcohol intake did not affect serum concentrations of etretinate. Unexpectedly, more frequent intake of vitamin A or provitamin A-rich food and supplements was associated with higher serum acitretin, whereas less frequent intake of vitamin A or provitamin A-rich food and supplements was associated with higher serum levels of etretinate in acitretin-taken patients. Despite preliminary data, inter-individual variations in serum retention of etretinate suggest the necessity of further research before applying the same guidelines to everyone to minimize unnecessary contraception.

Embryotoxic and Teratogenic Effects of Scolopendra Water Extract in Mice (오공(蜈蚣) 추출물의 태아 기형 및 모체 독성 마우스 시험)

  • Jeongmin, Lee;Jun-Ho, Song;Soong-In, Lee;Hyun Jun, Ki;In Sik, Shin;Sung-Ho, Kim;Changjong, Moon;Joong-Sun, Kim;Ji Hye, Lee
    • Herbal Formula Science
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    • v.31 no.1
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    • pp.21-28
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    • 2023
  • Objective : Scolopendra, a dried body of Scolopendra subspinipes mutilans, is one of Korean medicine. Several reports revealed that Scolopendra has therapeutic effects for arthritis, neuroinflammatory diseases and neuropathic pain. However, the fetal adaptive response or teratogenicity associated with administration of Scolopendra is unclear. Therefore, this study aimed to investigate the fetal toxicity effects that were induced following oral administration of Scolopendra water extract (SWE) in pregnant mice. Methods : The pregnant mice were administrated SWE at dosed of 0, 100, 500 and 1000 mg/kg/day during gestation day 0-18. The mortality, body weight and clinical signs of pregnant mice were observed throughout experimental period. Also, the mortality and malformations in foetus were examined. Results : No meaningful changes were observed in the mortality and clinical signs of pregnant mice between the normal control group and SWE administrated groups. Additionally, there are no significant changes in fetal mortalities, and malformations by SWE administration. conclusion : These results suggest that oral exposure to SWE during pregnancy at oral dosages up to 1000 mg/kg/day did not induce teratogenic toxicity in regard to fetal mortality and morphology.