摘要
目的探讨几种抗生素及其对应的差向异构体的毒性,及评价其环境风险。方法采用发光菌(费氏弧菌,Vibrio fischeri)的Microtox急性毒性测试方法,比较3种四环素类药物,即四环素(TC)、土霉素(OTC)和金霉素(CTC)及其对应差向异构体的急性毒性差异。结果3种四环素类药物及其差向异构体的半数效应浓度(EC50)值分别为:CTC6.119,差向金霉素(ECTC)20.24;TC 20.72,差向四环类(ETC)24.97;OTC 64.32,差向土霉素(EOTC)452.2 mg/L。显然,3种四环素类的EC50值以CTC、TC、OTC的次序递增;差向异构体也以同样的次序递增。与母体药物相比,相应的差向异构体毒性较低。差向异构体毒性较低(高EC50值)的原因在于差向异构化反应后4位碳上的二甲胺基形成空间位阻,从而在很大程度上抑制了药物与30S核糖体亚基末端的结合。结论四环素类药物在报道的环境暴露剂量下对底泥中的微生物存在毒性作用;同时其相应差向异构体的毒性效应在环境风险评价过程中不容忽视。
Objective A great deal of concern has been aroused about the environmental exposure of antibiotics. Hitherto, few obtained toxicological data cannot support the environmental assessment procedures. Methods This paper compared the acute toxicity difference between tetracyclines and their epi-isomers using the same microorganisms by Microtox acute test. Results Median effect concentration （ EC50 ） values（30min） of the six drugs were 6.119 mg/L for CTC, 20.24 mg/L for ECTC, 20.72 mg/L for TC, 34.97 mg/L for ETC,64.32 mg/L for OTC and 452.2 mg/L for EOTC, respectively. Obviously, EC50 values increased in the order of CTC, TC, and OTC. And the same order was observed for their epimers ： ECTC, ERIC, and EOTC. Compared with the corresponding parent drugs, epimers showed lower toxicity. The reason why epimers showed lower toxicity（higher EC50 ）than the corresponding tetracyclines lay in the fact that after epimerization the C-4 dimethyl amine could be a steric hindrance so as to greatly forbid the combining process of drugs. Conclusion On reported environmental concentrations tetracyclines affect the bacterial activity in sediments. And in environmental assessment, the effect of their epimers cannot be overlooked.
出处
《毒理学杂志》
CAS
CSCD
北大核心
2006年第5期279-281,共3页
Journal of Toxicology
基金
Science Faculty Strategic Research of Hong Kong Baptist University(FRG/03-04/Ⅱ-51)
中国科学院知识创新工程"集约化养殖场畜禽粪便的农用风险与污染控制"(kzcx3-sw-435)
江苏省自然科学基金前期预研项目(BK2004219)资助
关键词
发光菌
四环素
差向异构体
兽药
Luminescent bacterium
Tetracycline
Epimer
Veterinary medicine
