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Studies on the Mutagenicity and teratogenicity of Kuianchun and Its Potential Carcinogenicity Prediction

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Agricultural Sciences in China 2002年第2期1卷 213-220页

作者： LIANG Jian-ping, ZHANG Li, CAO Sui-zhong, ZHOU Li-xia, ZHOU Xue-hui LIU Zong-ping, WEI Chun-mei, MIAO Xiao-lin and WEI Zeng-quan(Institute of Animal Science and Veterinary Medicine , CAAS , Key Laboratory of New Medicine Project, Ministry of Agriculture Lanzhou 730050 Gansu Agricultural University, Lanzhou 730070 Institute of ModernPhysics , CAS , Lanzhou 730000) Institute of Animal Science and Veterinary Medicine CAAS Key Laboratory of New Medicine Project Ministry of Agriculture Lanzhou 730050 Institute of Modern Physics CAS Lanzhou 730000 Institute of Animal Science and Veterinary Medicine CAAS Key Laboratory of New Medicine Project Ministry of Agriculture Lanzhou 730050 Gansu Agricultural University Lanzhou 730070 Institute of Modern Physics CAS Lanzhou 730000

Kuianchun is a newly synthesized antibacterial and growth-promoting drug. This paper selected a battery of three short-term tests, including Ames test, micronucleus test and sperm abnormality test, to detect the mutagenicity of Kuianchun. The carcinogenicity prediction and battery selection method (CPBS method) was used to determine the probability of carcinogenicity of Kuianchun based upon the results of short-term tests mentioned above. In addition, traditional teratogenic test was selected to study teratogenicity of Kuianchun. In Ames test, Kuianchun showed mutagenic for Salmonella typhimurium strains TA98 and TA100 in the absence and presence of microsomal metabolic activation system (S9-mix). However, the mutagenicity was reduced by the addition of S9-mix. In micronucleus test, Kuianchun was administered intra-peritoneally to male mouse 30 hours and 6 hours before they were killed respectively. The result indicated that there was no significant difference on the number of micronucleated polychromatic erythrocytes (PCEs) in the mouse bone marrow induced by Kuianchun compared with the negative contrast (50% DMSO) (P>0.05). In sperm abnormality test, Kuianchun was administered through a gastric incubation to male mouse as a suspension in 2% Tween-80. The dosage levels were 450, 750, 1000 and 1500mg/kg per day for 5 days. The result indicated that the percentage of abnormal sperms induced by Kuianchun was not significant compared with the negative contrast (P > 0.05). In traditional teratogenic test, Kuianchun was given orally to pregnant mouse at 1730, 1/20 and 1/15 LD50 during 6 - 15days of pregnancy period (the LD50 = 9000mg/kg). No toxicity was found either on mother and embryo in mouse, and teratogenic effects were also not observed at all tested dosages.The probability of carcinogenicity of Kuianchun is 23.8%(6 = 0.238). The result demonstrated that Kuianchun is a non-carcinogen.

关键词： Kuianchun Mutagenicity teratogenicity Carcinogenicity Genetic-toxicity

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Studies on Mutagenicity and teratogenicity of Sarafloxacin

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Agricultural Sciences in China 2002年第1期1卷 108-113页

作者： SHEN Jian-zhong, SHEN Chuan, XIAO Xi-long, LI Jun-suo LIU Jin-feng, ZHANG Su-xia, ZHOU Zong-can and FU Juan-ling( College of Veterinary Medicine, China. Agricultural University, Beijing 100094 Beijing Medical University, Beijing 100083) College of Veterinary Medicine China Agricultural University Beijing 100094 Beijing Medical University Beijing 100083

Wistar rats and closed Kunming strain mice were selected to study the genetic toxicity of sarafloxacin. The results indicated that sarafloxacin had no significant toxic effect of an excreted mutagen in S. typhimurium strains, and did not induce significantly higher percentages of polychromatic erythrocytes with micronuclei (MNPCE) in mice. No significant mutagenic activity was observed in dominant lethal assay. At 5 and 50mg/kg b.w. , sarafloxacin did not produce significant effects on the reproductive parameters of litters and fetal growth, and did not induce the teratogenic effects on fetuses. Sarafloxacin induced some toxic effects on body length and skeletal growth in fetuses of 500mg/kg b.w., but had no significant dose - response relationship among the administered dosages of sarafloxacin. The results of the genetic toxicology above indicated that no evidence showing sarafloxacin was mutagenic and potentially teratogenic for animals.

关键词： Sarafloxacin Rat Mouse Mutagenicity teratogenicity Reproductive toxicity

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Histological observation on unique phenotypes of malformation induced in Xenopus tropicalis larvae by tributyltin

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Journal of Environmental Sciences 2012年第2期24卷 195-202页

作者： Junqi Liu Qinzhen Cao Jing Yuan Xiaoli Zhang Lin Yu Huahong Shi Key Laboratory of Urbanization and Ecological Restoration Department of Environmental Science East China Normal University Shanghai State Key Laboratory of Estuarine and Coastal Research ＇East China Normal University Shanghai 200062 China

Tributyltin（TBT）,a biocide used in antifouling paints,has shown strong teratogenic effects on Xenopus tropicalis embryos at environmentally relevant concentrations.X.tropicalis embryos were exposed to 50,100 and 200 ng/L tributyltin chloride for 72 hr.The histological changes were further observed on abnormal eyes,enlarged trunks,enlarged proctodaeums and absence of fins induced by TBT.The lens and the retinal layers of abnormal eyes were slightly or barely differentiated,and that the pigment epithelium was neither continuous nor smooth.The abdomens were full of undifferentiated gut tissue with yolk-rich inclusions in the tadpoles with enlarged trunks.The proctodaeums formed a bump-like or columnar structure.The mass of yolk-rich cells occupied the lumen,blocked the opening and even turned inside out of the proctodaeum.Both the ventral and dorsal fins in trunks and tails became narrow or even disappeared totally.Our results suggest that great changes of histology took place corresponding to the unique phenotypes.The gut tissue was poorly differentiated,which led to the failed elongation of the guts and subsequently the enlarged trunks.The enlarged proctodaeums were due to the undifferentiation of inner layer,the expansion of outer epidermal part and the absence of fins around them.In brief,the histological observations provided insights into the reason of the unique external malformations in some degree.

关键词： Xenopus tropicalis tributyltin teratogenicity histology proctodaeum fin

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Reproductive toxicity study with a novel deoxyguanosine analogue （Metacavir） in pregnant SD rats

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Frontiers of Medicine 2015年第1期9卷 82-89页

作者： Qihui Luo Zhengli Chen Anchun Cheng Mingshu Wang Jing Fang Xi Peng Li Tang Key Laboratory of Animal Disease and Human Health of Sichuan Province Ya 'an 625014 China Institute of Preventive Veterinary Medicine Sichuan Agricultural University Chengdu 611130 China

Our preliminary studies demonstrated that Metacavir has potential to become a new anti-HBV agent. The main targets of the toxic effects of Metacavir, in rhesus monkeys, were gastrointestinal tracts, liver, blood, and kidneys, which were not related to mitochondrial effects. In this study, the maternal toxicity, embryo-fetal developmental toxicity and teratogenicity were studied in pregnant Sprague-Dawley rats after intragastric administration of Metacavir （200, 100, 50, 0 mg/kg body weight） during the first 6-15 days of pregnancy. Slower weight gain was observed in 5 out of 21 rats subjected to a 200 mg/kg dose, as well as 2 out of 20 subjected to a 100 mg/kg dose. Compared with the solvent control group, the calibration weight gain in the 200 mg/kg and 100 mg/kg dosage groups respectively, during first 6-20 pregnant days were significantly different （P 〈 0.01, P 〈 0.05）. Significant dose related adverse effects to other reproductive parameters were not seen in F0 and F1, but the number of stillbirths in high dose group showed notably difference compared with the control group （P 〈 0.05）, while the litter incidence showed no difference. No Metacavir-associated pathological changes were observed. The present research indicated that at a dose of 200 mg/（kg·d）（i.e., 40 times the effective dose in rats）, Metacavir shows some maternal toxicity to SD rats. The embryotoxicity in the 200 mg/kg group encompass decreased fetal body weight, and higher fetal mortality rates, compared with the control group. However, the litter incidence showed no statistical difference. All the treated rats displayed normal bone development, no teratogenicity and without adverse effects on fetal development, thus indicating that below a dose of 200 mg/（kg· d） there is no teratogenic side effects.

关键词： deoxyguanosine analogue Metacavir pregnancy maternal toxicity embryo toxicity teratogenicity

Are herbal medicinal products less teratogenic than Western pharmaceutical products?

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Acta Pharmacologica Sinica 2002年第12期23卷 116-119页

作者： LEUNG Kwok-Yin LEE Yuk-Ping CHAN Ho-Yee LEE Chin-Peng Mary TANG Hoi-Yin China Department of Obstetrics & Gynaecology Department of Prenatal Diagnosis and Counselling Hong Kong SAR Pokfulam Road Queen Mary Hospital The University of Hong Kong Tsan Yuk Hospital the University of Hong Kong

AIM: To determine the use and teratogenicity of herbal medicinal products (HMP). METHODS: A retrospective study was conducted in a University hospital to compare the difference in the pattern of use and fetal outcomes between pregnant women who took HMP and Western pharmaceutical products (WPP). RESULTS: From 1995 Jan to 2001 Dec, 61 and 372 women took HMP and WPP one month before or during their current pregnancies respectively. There was an increase in the prevalence of pregnant women who took HMP from 0 % in 1995 to 0.8 % in 2001. Among HMP users, 51.6 %, 82.8 % and 58.6 % of them had low monthly family income (<15 000), low education level (secondary education or below) and were unemployed respectively. In comparison to WPP, pregnant women used smaller number of HMP (1.4 vs 3.0, P<0.01) at a later gestation (4.8 weeks vs 3.1 weeks, P <0.01) and within a shorter duration (11.1 d vs 47.9 d, P<0.01). The prevalence of congenital fetal abnormalities in the group of women who took HMP (3.3 %) was not sig

关键词： herbal medicine pregnancy teratogenicity

Paroxetine overdose during pregnancy

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Forensic Sciences Research 2021年第4期6卷 237-239页

作者： Selin Acar Hilal Erol Elif Keskin Arslan Nusret Uysal BarışKaradaş Tijen Kaya Temiz Yusuf Cem Kaplan Faculty of Medicine Department of Pharmacologyizmir Katip celebi UniversityizmirTurkey Terafar(izmir Katip celebi University Teratology information Training and research center)izmirTurkey

Paroxetine is a selective serotonin reuptake inhibitor(SSRI)used in the treatment of depression and anxiety disorders.In some epidemiological studies,slightly increased risks of major malformations and cardiac malformations have been reported following paroxetine exposure in the first trimester of pregnancy.However,such findings have been inconsistent.There is only one report of any overdose of an SSRI during pregnancy,and that involved escitalopram.The aim of this case report was to describe the impact of a paroxetine overdose in the first trimester of pregnancy on the health of the foetus.A 21-year-old mother of one child who was pregnant with a second child was prescribed 20 mg/day paroxetine hydrochloride for the treatment of anxiety/depression.The patient ingested 15 or 1620-mg tablets of paroxetine hydrochloride(300-320 mg)during the 5th week of pregnancy as a suicide attempt.Within 15 min of ingestion,she was admitted to hospital and treated for intoxication.No evidence of maternal SSRI intoxication was observed after treatment.The patient consulted our teratology information service for further risk assessment regarding possible major congenital malformations following the paroxetine overdose.We were unable to find previous reports of paroxetine overdose during pregnancy in the literature.The timely administration of the overdose treatment and the lack of maternal intoxication symptoms were considered positive for the foetal well-being,and the patient was referred for perinatology and psychiatry follow-ups.A healthy,3500-g male infant was born at 38 weeks’gestation,and his development at the age of 2 years was normal.This is the first reported case of paroxetine overdose during pregnancy.Comprehensive studies are needed to evaluate pregnancy outcomes after SSRI overdose.

关键词： Forensic sciences forensic toxicology paroxetine overdose teratogenicity case report

Managing reproductive problems in women with epilepsy of childbearing age

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Acta Epileptologica 2021年第1期3卷 195-204页

作者： Wanlin Lai Shixu He Dong Zhou Lei Chen Department of Neurology West China HospitalSichuan UniversityChengdu 610041China

Girls and women constitute nearly 50%of all epilepsy cases.Apart from the disease symptoms,epilepsy and antiseizure medications(ASMs)may also affect the reproductive function,pregnancy and even the health of their offspring.Therefore,it is very important to identify and summarize the problems and risks for women with epilepsy(WWE)of childbearing age,and offer internationally recognized methods through multidisciplinary collaboration.In this review,we summarize the reproduction-related problems with WWE and propose multidisciplinary management by epileptologists,gynecologists and obstetricians,as well as other experts,from preconception to delivery.Large,multicenter registries are needed to advance our knowledge on new ASMs and their effects on WWE and their offspring.

关键词： Women with epilepsy Reproduction Antiseizure medications teratogenicity Offspring Seizure Childbearing

药物的畸胎形成性(teratogenicity)的評价

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山西医学杂志 1965年第4期 83-84页

作者：景崙彦祖

药理学中最棘手的问题是解释药物的慢性毒性,近来新的更复杂的问题是对药物畸胎形成性的评价。以前仅评价药物对生殖的影响,从未系统研究畸胎形成作用。达利陀迈(Thalidomide)事件使药理界大为震惊,开始重视胚胎学研究。研究历史已久。1... 详细信息

药理学中最棘手的问题是解释药物的慢性毒性,近来新的更复杂的问题是对药物畸胎形成性的评价。以前仅评价药物对生殖的影响,从未系统研究畸胎形成作用。达利陀迈(Thalidomide)事件使药理界大为震惊,开始重视胚胎学研究。研究历史已久。1950年胚胎学家借各种类型的物质引起先天性畸形,如物理因素、病毒、维生素缺乏或过多、抗代谢剂或固醇类。这些成果在1962年医生开始研究药物引起畸胎

关键词：畸胎动物先天性畸形 teratogenicity 药物形成性

Cadmium-induced teratogenicity:association with reactive oxygen species(ROS) - mediated endoplasmic reticulum stress in placenta

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Cadmium-induced teratogenicity:association with reactive oxy...