Effects of 2,3,5,6-Tetramethylpyrazine on alcohol-induced injury in liver cells and on the early life stages of zebrafish (Danio rerio Hamilton, 1822)

Background@#Alcoholic liver disease (ALD) is a major health problem referring to the collection of liver damage caused by excessive alcohol intake. The search for effective and safe alternatives for compounds from plants to protect the liver from extensive damages and delay the progress to a disease is still a big effort done in the scientific community. 2,3,5,6-Tetramethylpyrazine (TMP) is a compound found in a Chinese herbal medicinal plant, Ligusticum chuanxiong Hort and in some other plants. @*Objective@#This study was done to assess the hepatoprotective effects of TMP against ALD using histopathological analysis of zebrafish livers subjected to different exposure groups. TMP has been mainly used for the treatment of cardio- and cerebrovascular diseases due to its antioxidant, anti-inflammatory, and antiapoptotic properties. @*Methodology@#Adult male zebrafish were exposed to three TMP concentrations (40, 60, and 80 mg/L TMP) and to 1% v/v of ethanol. The dissected livers of the zebrafish were processed for fixing on glass slides using the H&E stains and were observed under the light compound microscopes for scoring. The safety of the TMP to the early life stages of the zebrafish was tested using the Zebrafish Embryotoxicity Test (ZFET). @*Results@#Results showed that TMP was able to dose-dependently decrease mean scores for the four parameters diagnostic of ALD, i.e., steatosis, inflammation, cell death, and ballooning degeneration. These scores were comparable to those of the untreated group (no ethanol + no treatment) and positive control (ethanol + Hepasil DTXTM), with all groups' scores being statistically different from those of the negative control group (ethanol + no treatment) (p<0.05). Results for the ZFET showed that incidence of embryo mortality as well as teratogenic malformations of embryos exposed to TMP were significantly lower compared to the positive control group. @*Conclusion@#The hepatoprotective role of TMP was implied because anomalies such as cholestasis, vessel congestion, and hemorrhage were only observed in the ethanol-treated group and not in the other groups. In the analysis of the early development of the embryos using the Zebrafish Embryotoxicity Test (ZFET), TMP was found to be non-toxic and non-teratogenic at concentrations used for liver treatment. These initial findings on TMP provided justification for its plausibility as a hepatoprotective compound against alcoholic liver diseases (ALD).

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.

Comparative toxicological analysis of Metformin (Biguanide) and Glibenclamide (Sulfonylureas), using Zebrafish Embryotoxicity Test (ZFET)

Background and Objective@#Type 2 (T2DM) and gestational diabetes mellitus (GDM) among pregnant Filipinos have been increasing over the years because of lifestyle westernization. While insulin has been the safe mainstay when dietary measures fail to maintain normoglycemia during pregnancy, recent studies have suggested oral hypoglycemic agents (OHAs) such as metformin and glibenclamide, may offer cheaper and efficacious alternatives. The problem however, is the passage of these drugs through the placenta which may pose possible danger towards the development of the growing embryo. The proposed study aims to evaluate and compare the embryotoxic and teratogenic potentials of the varying concentrations of the two PhilHealth covered oral hypoglycemic agents in the Philippines, namely metformin (biguanide) and glibenclamide (sulfonylureas). @*Methodology@#In this study, a comparison on embryotoxic potentials of metformin and glibenclamide was conducted using zebrafish embryotoxicity test (ZFET) across concentrations found in fetal (10, 20, 100, 500, 1000, 2000 μg/L) and maternal serum (10, 20, 100, 500, 1000, 2000 mg/L). @*Results and Conclusions@#Results revealed that metformin showed no significant (p>0.05) lethal effects, but revealed significant risk for teratogenicity, specifically decreased head and tail lengths and advanced hatching. Conversely, glibenclamide revealed significant potential for lethal (e.g., coagulation) and teratogenic effects including pericardial and yolk sac edema, spinal deformity and increased tail length. Comparative evaluation between the two OHAs reveal that glibenclamide has significantly (p<0.05) higher lethal and teratogenic effects. Together, our results suggest that the use of metformin over glibenclamide is favorable for safety testing in pregnant women suffering T2DM and GDM for the benefit of expanding treatment options for these diseases.

Genotoxicity and Embryotoxicity Study of Bicyclol Methyl Ether, Main Impurity in Bicyclol / 中国结合医学杂志

OBJECTIVE@#To assess the genotoxicity and embryotoxicity of bicyclol methyl ether (BME), the main impurity in bicyclol.@*METHODS@#Five concentrations of BME (0.5, 5, 50, 500 and 5000 μg/plate) were used in the Ames test to detect gene mutation. In the chromosome aberration test, Chinese hamster lung cells were used to detect chromosomal aberration of BME (15, 30, 60, 120 μg/mL) with or without S9 mixture. Embryotoxicity test was also conducted to determine any embryotoxicity of BME (7.5, 22.5, 67.5 μg/L) using zebrafish embryos.@*RESULTS@#No significant differences were observed in the Ames test and the chromosome aberration test in the BME groups compared with the vehicle control group. The zebrafish embryos toxicity test also showed no embryo development toxicity of BME, including hatching rate, body length, pericardial area and yolk sac area.@*CONCLUSIONS@#Bicyclol methyl ether has no genotoxicity in vitro and embryotoxicity in zebrafish embryos, and the impurity in bicyclol is qualified.

Impact of Nicotine Exposure on Hair Cell Toxicity and Embryotoxicity During Zebrafish Development

OBJECTIVES: Nicotine has various adverse effects including negative impacts associated with maternal exposure. In the current study, we examined nicotine-induced damage of hair cells and embryotoxicity during zebrafish development. METHODS: Zebrafish embryos were exposed to nicotine at several concentrations (5, 10, 20, and 40 μM) and embryotoxicity were evaluated at 72 hours, including hatching rate, mortality, teratogenicity rate, and heart rate. Hair cells within the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) neuromasts were identified at 120 hours. Apoptosis and mitochondrial damage of hair cells were analyzed using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling) and DASPEI (2-[4-(dimethylamino)styryl]-N-ethylpyridinium iodide) assays, respectively, and changes of ultrastructure were observed by scanning electron microscopy. RESULTS: The control group without nicotine appeared normal with overall mortality and teratogenicity rate < 5%. The hatching rate and mortality rate was not significantly different according to nicotine concentration (n=400 each). The abnormal morphology rate (n=400) increased and heart rate (n=150) decreased with increasing nicotine concentration (P < 0.05). Nicotine-induced hair cell damage significantly increased as nicotine concentration increased. A significantly greater number of TUNEL-positive cells (P < 0.01) and markedly smaller DASPEI area (P < 0.01) were shown as nicotine concentration increased. CONCLUSION: The current results suggest that nicotine induces dose-dependent hair cell toxicity in embryos by promoting apoptosis and mitochondrial and structural damage.

A study on teratogenic effects of Chimonanthus salicifolius S. Y. Hu extract on SD rats / 预防医学

Objective To study maternal toxicity, embryotoxicity and teratogenecity of Chimonanthus salicifolius S. Y. Hu in SD rats.Methods A total of 64 successfully mated female SD rats were randomly divided in to 4 groups (16 per group), in which 3 experimental groups were daily treated with 3.75, 7.5 and 15.0 g/kg. bw test substance by lavage from 7th to 16th day during gestation respectively. Body weight and general conditions of the pregnant rats were recorded during the study. On the 20th day in pregnancy, the rats were anatomized and examined grossly, the fetuses were removed and counted, weight, length, visceral and skeletal changes were then examined. Results There was no significant difference in the conception rate, total weight gain during the pregnancy and the number of living, dead and resorbed fetuses between each dosage groups and the control group (P>0.05) . The number of the rib, sternum, the fifth sternum punctated and the parietal bone which were ossified defectively all showed no difference among the four groups (P>0.05) . Conclusion Chimonanthus salicifolius S. Y. Hu extract had no obvious maternal toxicity, embryotoxicity and teratogenecity in SD rats under this experiment condition.

Evaluation of embryo toxicity of Shuanghuanglian based on human placental barrier model / 中国药理学与毒理学杂志

OBJECTIVE To evaluate the embryo toxicity of Shuanghuanglian (SHL) by the combination of a human placental barrier model and embryonic stem (ES) cell test model.METHODS A human placental barrier model was set up by placenta slice culture and Ussing chamber.SHL 0.2,0.4,0.8,1.6,3.2,6.4 and 12.8 g· L-1 was added into the maternal side of the human placental model,respectively.All the media was collected respectively from the matemal side and fetal side 60 min later and taken as the SHL containing medium.ES cells (D3 line) and embryonic fibroblast cells (BALB/c 3T3) were cultured with the SHL containing medium respectively from the maternal side and the fetal side for 10 d.Cell viability was detected by MTT assay,and 50％ survival inhibitory ratio of ES and 3T3 cells by SHL was calculated.ES cells were incubated with the SHL containing medium from the matemal side or fetal side when they differentiated to cardiac myoblasts using hanging drop-suspension-attachment method.Messenger RNA of myosin heavy chain genes (β-MHC) was detected by Q-PCR for differentiation ratio,and 50％ differentiation inhibitory ratio of ES cells by SHL was calculated.A statistics formula was used for prediction of SHL embryotoxicity potential.RESULTS The IC50 of SHL in the matemal side of the human placental model for 3T3 cell survival,ES cell survival and ES differentiation was 1.97,0.84 and 0.48 g· L-1,respectively.According to the criteria for embryo toxicity evaluation,SHL had weak embryo toxicity.However,the IC50 of SHL in the fetal side of the human placental model for 3T3 cell survival,ES cell survival and ES differentiation was 3.19,2.57 and 0.95 g· L-1,respectively.According to the criteria for embryo toxicity evaluation,the supernatant containing SHL that went through the placental barrier had no embryo toxicity.CONCLUSION SHL is safe in the test concentration range during pregnancy.It is more scientific to evaluate embryo toxicity of drugs by ES cell test with the samples obtained through the placental barrier during pregnancy.

Embryonic stem cell test for the study of the embryotoxicity of hydroquinone / 国际检验医学杂志

Objective To establish a model of embryonic stem cell test(EST)and utilize this model to evaluate the embryotoxici-ty of hydroquinone.Methods Mouse 3T3 fibroblasts and mouse embryonic stem(ES)cells(ES-E14TG2a)were cultured in vitro, and methyl thiazolyl tetrazolium(MTT)test was performed to detect the cytotoxicity of 3T3 cells and ES-E14TG2a cells induced by the positive control(5-fluorouracil),negative control(penicillin G)and tested compound(hydroquinone).The concentrations of the test compounds that inhibited 50% viability of ES-E14TG2a cells(IC50 ES)and 3T3 fibroblasts (IC50 3T3)were calculated.The hanging-suspension-adherent culture systems were used to induce embryonic stem cells into cardiomyocytes,and the concentrations of test compounds that caused 50% inhibition of differentiation of ES-E14TG2a cells into cardiomyocytes (ID50 ES)was calculated. The embryotoxic potential of hydroquinone was classified by prediction model of the embryonic stem cell test.Results The prolif-eration of ES-E14TG2a and 3T3 cells were inhibited by hydroquinone,of which the IC50 3T3 and IC50 ES values were (5.97±0.48) and (2.57±0.10)μg/mL respectively.The differentiation of ES-E14TG2a cells were also inhibited by hydroquinone,of which the ID50 ES was (3.77±0.31)μg/mL.Hydroquinone was evaluated as a strong embryotoxicity chemical by prediction model of EST. Conclusion Hydroquinone exhibits a strong embryotoxicity.

Embryotoxicity and Toxicokinetics of the Antimalarial Artesunate in Rats

This study was conducted to investigate the potential embryo-fetal toxicity and toxicokinetics of the antimalarial agent artesunate (ARTS) in Sprague-Dawley rats. Pregnant rats were administered ARTS daily from gestational day 6~15 via oral gavage, at test doses of 0, 2, 4, or 8 mg/kg (22 females per group). The fetuses were examined for external, visceral, and skeletal abnormalities on gestational day 20. With regard to the dams, there were no deaths, treatment-related clinical signs, changes in body weight, or food intake in any of the treatment groups. There were no treatment-related gross findings at necropsy in any treatment group. In the 8 mg/kg group, there was a decrease in gravid uterine weight and in the weight of female fetuses. There was also an increase in fetal deaths (primarily late resorptions) and an increase in post-implantation losses (37%) at 8 mg/kg. An increase in the incidence of visceral and skeletal variations at 4 and 8 mg/kg was observed. These defects included minor changes in the appearance of the kidney and thymus, as well as absent ribs or thoracic vertebrae. Toxicokinetics were assessed in a parallel study, using 4 mated females per group. Using liquid chromatography-mass spectrometry (LC-MS) analysis, the concentration of ARTS and its metabolite dihydroartemisinin (DHA) were quantified in plasma from rats on gestational days 5, 6, 10, and 15. Amniotic fluid was assayed for ARTS and DHA on gestational day 15. There was evidence of rapid conversion of ARTS to the metabolite DHA in maternal plasma, since ARTS could not be consistently detected in plasma at the three doses tested. ARTS and DHA were not detected in amniotic fluid at gestational day 15, indicating limited placental transfer of the two agents. The embryo-fetal no-observable-adverse-effect level (NOAEL) of the test item was considered to be 8 mg/kg/day for dams, and 2 mg/kg/day for embryo-fetal development.

Ketoconazole- and fluconazole-induced embryotoxicity and skeletal anomalies in wistar rats: a comparative study

Ketoconazole and fluconazole are two broad-spectrum azole antifungals used for the treatment of superficial and systemic mycoses. Embryotoxicity and teratogenicity have been reported in some studies when those drugs are administered at high doses to pregnant rats. The aim of this study was to present a comparative study of embryotoxic effects as well as the skeletal anomalies in fetuses of Wistar rats which received ketoconazole and fluconazole at teratogenic doses on gestational days (GD) 6 through 15 (organogenesis period). On gestational day (GD) 21, the dams were euthanized and examined for standard parameters of reproductive outcome. Fetuses were stained with alizarin red and the bones of the head, trunk, forelimb and hindlimb were examined for detection of skeletal anomalies. The frequency of skeletal anomalies in the ketoconazole-treated group was significant when compared to the fluconazole and the control group.

O cetoconazol e o fluconazol são dois antifúngicos azólicos, de amplo espectro, utilizados no tratamento de micoses superficiais e sistêmicas. Alguns estudos relatam a embriotoxicidade e teratogenicidade induzidas por estes fármacos quando os mesmos são administrados em altas doses a ratas prenhes. O objetivo deste trabalho foi apresentar um estudo comparativo dos efeitos embriotóxicos e das anomalias esqueléticas em fetos de ratas Wistar que receberam cetoconazol e fluconazol em doses teratogênicas do 6º ao 15º dia gestacional (GD) (período da organogênese). No 21º GD as ratas foram eutanaziadas e examinadas quanto aos parâmetros padrões de performance reprodutiva. Os fetos foram corados com vermelho de alizarina e os ossos da cabeça, do tronco e dos membros anteriores e posteriores foram examinados para a verificação de anomalias esqueléticas. A freqüência de anomalias esqueléticas no grupo tratado com cetoconazol foi significante quando comparada à dos grupos fluconazol e controle.

Vero Cell Co-culture Counteracts the Detrimental Effects of Hydrosalpinx Fluid on the Development of Mouse Embryos in vitro

Recent studies have suggested that the hydrosalpinx has a negative effect on pregnancy outcome, with markedly diminished implantation and increased early pregnancy loss. Fluid from the hydrosalpinx may leak into and accumulate in the uterine cavity. It is not clear, however if this creates a hostile local environment in the uterus for embryo implantation or exerts a direct embryotoxic effect. This study was conducted to investigate the detrimental effects of hydrosalpinx fluid (HSF) on the development of mouse embryos in vitro and to demonstrate whether Vero cells overcome these adverse effects. HSF was collected from three women with bilateral hydrosalpinx at the time of laparoscopic surgery. Collected fluid was centrifuged and the supernatant was frozen at -20degrees C. For co-culture, Vero cells were commercially obtained in a frozen state and cultured using Ham's F10 medium. Single-cell mouse embryos (B6CBAF1) were cultured for 5 days in 0, 0.4, 0.8, and 1.2% of HSF in media with and without Vero cells and examined daily to record the number of embryos reaching expanded blastocyst and hatching stage. Co-culture of mouse embryos with Vero cells at 0.8% HSF concentration significantly enhanced embryo development, but not at 1.2% hydrosalpinx fluid concentration. These results suggest that HSF is highly embryotoxic and Vero cells are likely to overcome these detrimental effects to some degree.

Effect of human hydrosalpinx fluid on mouse in in vitro fertilization and embryo development / 대한산부인과학회잡지

OBJECTIVE: To ascertain if hydrosalpinges are associated with reduced pregnancy rates and increased pregnancy loss after IVF-ET, a study was conducted. Increased volume and leakage of hydrosalpinx fluid may exert negative effects on follicular development and embryo quality and/or render the uterine environment hostile to embryogenesis. This study was undertaken to examine the effect of hydrosalpinx fluid on mouse embryogenesis in vitro. METHODS: The study was designed by comparison of mouse embryo blastulation rate in media containing increasing concentrations of hydrosalpinx fluid. In vitro fertilization rate and the development of one-, two-, four-cell mouse embryos in medium containing 0% (Control), 0.3%, 0.6%, 0.9%, 5%, 10% and 20% of human hydrosalpinx fluid-containing media was observed. RESULTS: In vitro fertilization and culture of mouse embryo at 0% (control), 0.3%, 0.6%, 0.9%, 5%, 10%, 20% hydrosalpinx fluid concentrations demonstrated significantly lower blastulation rate at each level compared with the controls (p<0.05). In vivo fertilization and culture of embryo at the same increasing concentration of hydrosalinx fluid showed the same results (p<0.05). And the difference of each embryo development (zygote, 2cell, 4cell) was not significant. CONCLUSION: Hydrosalpinx fluid is highly embryotoxic. Procedures such as salpingectomy or proximal tubal occlusion to circumvent the passage of hydrosalpinx fluid into the uterine cavity may have beneficial effects on the developmental environment for embryos in vivo.

Protective effects of garlic juice against embryotoxicity of methylmercuric chloride administered to pregnant Fischer 344 rats

In order to investigate the beneficial effects of 0.5 or 1.0 g/kg Korean garlic juice against the embryotoxicity of 20 mg/kg methylmercury chloride (MMC, CH3HgCl), pregnant Fisher 344 rats were simultaneously orally administered on day 7 of gestation. On day 20 of gestation the dams were laparotomized under ether anesthesia, and the fetuses were removed and examined for toxicity of methylmercury. Garlic juice depressed the toxicity in terms of some parameters. In the case of simultaneous treatment with 0.1 g/kg garlic juice and MMC, rates of increase were 17.5% in maternal body weight, 13.2% and 41.9% in fetal and litters' weight respectively, and 37.0% in fetal survival rate. Decreasing rates were 10.0% in maternal death rate, and 6.9% and 31.3% in pre- and post-implantation loss respectively. Decreasing rates of mercury levels in dams were 67.2% in liver, 57.6% in brain, 47.2% in kidney, 42.1% in spleen and 40.9% in blood. As well, decreasing rates of mercury level in fetuses were 54.9% in all body burden, 55.9% in liver, 46.7% in kidney and 37% in brain, respectively. The number of fetal ossification centers were reduced by 23.8% to 58.0% following simultaneous treatment with 1.0 g/kg garlic juice. These findings indicated that garlic juice effectively inhibited the embryotoxicity of methylmercury in pregnant Fischer 344 rats.

Effect of Antioxidant on the Toxicity Induced by Cadmium in Preimplantatio Embryos In Vitro / 대한산부인과학회잡지

In order to elucidate the mechanism of oxidative damage of cadimu(Cd) on culturedmouse preimplantation embyors.The embryotoxocity of Cd was examined after cultured mouse preimplantation embryoswere exposed to various concentrations of CdCl2. In addition, the protected effect of antioxidant,catalase against Cd-induced embryotoxicity was investigated.CdCl2 decreased the development of cultured mouse preimplantation embryos in dose andtime-dependent manners, and also oxidative damage was involoved in Cd-induced embryotoxicityin mouse preimplantation embryos by the prevention of catalase on Cd-induced toxicity.

Effect of Antioxidant on the Toxicity Induced by Cadmium in Preimplantatio Embryos In Vitro / 대한산부인과학회잡지

In order to elucidate the mechanism of oxidative damage of cadimu(Cd) on culturedmouse preimplantation embyors.The embryotoxocity of Cd was examined after cultured mouse preimplantation embryoswere exposed to various concentrations of CdCl2. In addition, the protected effect of antioxidant,catalase against Cd-induced embryotoxicity was investigated.CdCl2 decreased the development of cultured mouse preimplantation embryos in dose andtime-dependent manners, and also oxidative damage was involoved in Cd-induced embryotoxicityin mouse preimplantation embryos by the prevention of catalase on Cd-induced toxicity.

Joint Toxic Effects of Benzene and Formaldehyde on Embryos of Mice at the Phase of Pre-implantation / 环境与健康杂志

0.05),while the numbers of embryos(P

Study on Embryotoxicity and Teratogenicity of Monocrotophos in Mice / 环境与健康杂志

Objective To study the embryotoxicity and teratogenicity of monocrotophos in mice.Methods Sixty pregnant Kunming mice were randomly divided into four groups,15 in each:three groups were exposed to the monocrotophos at the doses of 0.05,0.10 and 0.20 mg/kg,10 ml/kg through gavage,during the period of organ formation(from 7th day to 16th day),once a day and the control group to distilled water.The pregnant mice were weighted in day of 0,6,12,18,and 20,and were sacrificed on 20th day of pregnancy.The numbers of living,dead and absorbed fetus were counted,and the uterus and placenta were weighted.The deformity examination was conducted.Results The maternal body weight of exposure groups were lower than those of control group in 12,18 and 20 day of pregnancy.With the increased doses of monocrotophos,the weights of pregnant mice showed a downward trend.Compared with the control group,the rates of dead fetus and absorbed fetus increased significantly,and the rates of living fetus,the fetal body weight and body length,tail length and placental weight decreased significantly(P

Effects of Perinatal Diphenylchloroarsine Chloride Exposure on Livability and Reproductive Function of F1 Generation Rats / 环境与健康杂志

Objective To study the effects of perinatal exposure of diphenylchloroarsine chloride(DA)on the livability and reproductive function of F1 generation rats.Methods The pregnant rats were treated with DA by gavage at 0(solvent control),0.63(low dose),0.94(medium dose),1.89(high dose)mg/(kg?day)from day 6 of pregnancy to day 15 of lactation.The general condition,the change of body weight and abnormity of main organs of the F0 pregnant rats and F1 young rats were observed,and the livability and abnormity of reproductive function of F1 young rats were examined.Results The results indicated that compared with the negative control,the increasing amounts of the body weights of the F0 maternal rats and the livability of F1 young rats aged 4 day significantly decreased at 0.94 mg/kg and 1.89 mg/kg,the livability in lactation period obviously reduced at 1.89 mg/kg,and the rate of absorbed fetus in F1 pregnant rats increased at 1.89 and 0.94 mg/kg.Conclusion DA exposure may have an adverse effect on livability and reproductive function of the F1 offspring when the dosage is no fewer than 0.94 mg/kg.

A Teratological Study of Sprague-Dawley Rats with 3 (or 8)-(l-Methoxyethyl)-8 (or 3)-hydroxyethyl-deuteroporphyrin / 第二军医大学学报

The potential embryotoxicity, developmental toxicity and teratogenic effects of (3 or 8)-(l-methoxyethyl)-8 (or3)-hydroxyethyl-deuteroporphyrin (PsD-044) were investigated in Sprague-Dawley rats with the conventional teratological method in vivo. According to the recommending clinical dosage, PsD-044 was administered intravenously at 20, 10 and 5mg/kg, as compared to the negative control with saline and the positive control with sodium pentachlorophenolate, respectively on the 10th day of the gestation. Eighty-one pregnant rats and 803 fetuses were examined. The results suggest that the maternal toxicity, embryotoxicity and teratogenic effects of PsD-044 were not found, however, the malformation induced by known teratogen was as high as 14.1%.

THE EFFECTS OF ACTINIDIA CHINENSIS PLANCH ON THE PREVENTION OF CANCER IV. The Blocking Effects of Concentrated Juice on theN-nitroso Ethyl Urea (NEU) in Vivo——RatEmbryotoxicity Test / 营养学报

In order to observe the effect of Actinidia chinensis Planch fruit juice on blocking the formation of N-nitrosamide in vivo, 99 pregnant Wistar rats were divided into five groups. The rats of each group were orally given ni-trosamide precursor ethylurea (0.25, 0.50, 1.00, 2.00 4.00 mmol/kg) and NaNO2 (0.125, 0.25, 0.50, 1.00, 2.00 mmol/kg) respectively once a day for three days, on the 7th, 8th and 9th day of pregnancy. Half of the rats in. each group were administrated two precursors and a 4% starch solution, while the other half were administrated two precursors and the tested fruit juice.In the groups without the juice, NEU was formed in vivo, which led to a high mortality of embryos. The embryolethality was 5.21%, 43.66%, 71.7%, 85.8% and 100% respectively, and 4 pregnant rats died in the highest dosage group. However, the rats who received both the two precursors and the tested fruit juice, the living embryos and embryolethality were similar to the control groups except the highest dosage group. The none treatment group and groups only given one of the precursors were done as control groups. The results suggested that the concentrated juice could block the formation of NEU in vivo and prevent the embryotoxicity of NEU.