Toxicity Of Cyclophosphamide To Reproductions In SD Rats

Cyclophosphamide (cyclophosphamide, CP)is also known as ring phosphorus nitrogenmustard, endoxan and vindesine. It is a kind of nitrogen mustard compounds,and commonlyused clinical immunosuppression and antineoplastic drugs.But its side effects is stronger,especially with strong teratogenic and mutagenic effects, it can affect the human reproductivecells and fetal growth and development, and cause serious damage to human reproductivehealth.To explore cyclophosphamide reproductive toxicity in SD rats, and the correlation oftoxicity and drug dose.Designing a solvent control group, cyclophosphamide, low, medium,high dose groups,respectively for the following experiments.(1) Exploring the toxicity of cyclophosphamide on SD rat fertility and early embryonicdevelopment.176healthy SD rats of6-7weeks old were selected, and were randomly dividedinto4groups, and each group has44rats,male and female half and half.Then they were givensubcutaneous injection by administered program and observed clinical symptoms andpathological changes, counting males fertility, females sexual cycle,pregnancy rate andmortality and stillbirths in each dose group. The experimental results show thatcyclophosphamide low, medium and high dose groups have significant toxic effects on SD ratfertility and early embryonic development. Toxic effects enhanced with thecyclophosphamide dose increased, dose and toxicity has obvious dose-effect relationship.(2) Experiment of cyclophosphamide on SD rats embryo-seed developmentaltoxicity.According to weigh,100healthy pregnant SD rats were at random divided into4groups,no less than20each group.According to the procedures for subcutaneously, observeclinical manifestations, statistics of each dose group of pregnant rat body weight, food intake,litter weight, corpus luteum number, bed number, number of live births and the number ofdead and absorption index, gender, body weight, body length, the appearance of fetal ratsdeformity, gut malformation and bone abnormalities such as index. The experimental resultsshow that the cyclophosphamide low, medium and high dose groups each-in rat embryo fetalseed development has obvious toxic effects, with increasing dose cyclophosphamide tomedicine, toxicity, enhanced drug dose and toxic has obvious concentration-responserelationship.(3) Experiment of cyclophosphamide on SD rats perinatal period toxicity. According toweigh,100healthy pregnant SD rats were at random grouped into4, no less than20eachgroup, subcutaneous injected. The statistic results of clinical manifestations were included: weight, food intake, and reaction after the drug given, pregnancy rate, mortality, the situationof parturition and nursing etc during pregnancy and nursing. Weight, exterior deformation,survival rate of birth and nursing, sex percentage, index of physical development and neuraldevelopment were recorded during nursing. Male and female rats at1:1mate after sexualmaturation of F1generation.After mating, the males euthanasia, pregnant rats continue toraise until15d and autopsy, examine the fertility ratio of F1generation, male pregnancy rateof female mice, weight, food intake, weight of overall rates and ovary, the number of corporalutea and implantation, loss ratio after and before implantation of pregnant rate and thesurvival rate, stillbirth rate, absorption rate of F2generation and so on.The results show thatthe low, middle, high cyclophosphamide group has obvious toxic effects on rats in perinatalperiod. Toxicity enhanced with dose of cyclophosphamide increasing, which demonstrate thatdrug dose and toxic has obvious concentration-response relationship.Three reproductive toxicity test showed that the cyclophosphamide at low, middle, highdose have toxic effects on fertility of SD rats and early embryonic development, fetaldevelopment, perinatal period, having obvious concentration-response relationship.