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Studies On Teratogenicity And Mutagenesis Of Aspirin Eugenol Ester

Posted on:2014-06-28Degree:MasterType:Thesis
Country:ChinaCandidate:X J KongFull Text:PDF
GTID:2253330401978650Subject:Basic veterinary science
Abstract/Summary:PDF Full Text Request
Aspirin eugenol ester (AEE)was a new NSAID, was synthesized by acyl chloride method using aspirin and eugenol as the raw materials.The drug can decrease the gastrointestinal irritation of aspirin and increase the stability of eugenol.In this paper, using a method of combining the experimental and computer simulation to research the mutagenicity in vitro and in vivo and the developmental toxicity potential, the results will provide a theoretical basis for the AEE safety evaluation.Using the toxicity estimation software TOPKAT to predict the mutagenicity and the development toxicity potential,the result of mutagenicity (Ames test) was negative,and the structure of AEE was in the OPS,this means creditableness. The result of developmental toxicity potential was positive,and the structure of AEE was out of the OPS,this means need the experimental to validate.The genotoxicity of the aspirin eugenol ester(AEE) was examined by the three standard genotoxicity assays. They were the Salmonella typhimurium mutagenicity assay(Ames test), the mouse bone marrow micronucleus assay and the mice sperm abnormality test. In the Ames test, Salmonella strains TA97,T A98, TA100, TA102and TA1535were treated with or without the metabolic activation with an S9fraction from Acroclor-induced rat liver, and the dose of AEE was5mg/plate,2.5mg/plate,1.2mg/plate,0.625mg/plate,0.3175mg/plate. In five tested strains, a2-fold in the number of his+revertants/plate was not found. In the mammalian erythrocyte micronucleus assay, sixty wistar rats with the dose of5000mg/kg,2500mg/kg,1250mg/kg were used, and AEE did not induce any significant increase in micronucleated erythrocytes after24h(p<0.01). In the mice sperm abnormality test, fifty male mice were used and the dose of AEE were5000mg/kg,2500mg/kg,1250mg/kg. AEE did not induce any significant increase in sperm abnormality (p<0.01). Contributing these results,we can suggest that AEE is non-genotoxic in vivo or in vitro.A teratogenicity test of AEE was carried out in SD (Sprague Dawley) rats to assess the safety of AEE on the reproduction and development of SD rats.. Sixty pregnant SD rats were divided into negative control, positive control and three experiment groups, and AEE was administered by gavage during gestation from day7to day16in the3experiment groups, respectively. The effects of AEE on appearance abnormity, skeletal development and entrails developmental of fetuses were examined. Form the results, the high dose of AEE has developmental toxicity, the middle dose and low-dose has no developmental toxicity.
Keywords/Search Tags:Aspirin Eugenol Ester, TOPKAT, Mutagenesis, Teratogenicity
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