Toxic effects of strychnine and strychnine N-oxide on zebrafish embryos  

作　　者：LI Yu QI Xu YANG Yu-Wei PAN Yang BIAN Hui-Min 

机构地区：[1]Jiangsu Key Laboratory for Chinese Medicine Processing, College of Pharmacy, Nanjing University of Chinese Medicine [2]Department of Preclinical Medicine, University of Chinese Medicine,Nanjing [3]Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University,Nanjing

出　　处：《Chinese Journal of Natural Medicines》2014年第10期760-767,共8页中国天然药物（英文版）

基　　金：supported by The Opening Project of Jiangsu Key Laboratory for Chinese Medicine Processing(ZYPZ010);the National Natural Science Foundation of China(81373295)

摘　　要：AIM: The application of strychnine(S) is limited due to its toxicity; strychnine N-oxide(SNO) is a derivative of strychnine. The aim was to employ zebrafish embryos to investigate and compare the developmental toxicity induced by S and SNO. METHODS: The toxicity of S and SNO was examined through the hatching rate and survival rate. Morphological changes of the zebrafish were observed with a dissecting microscope. Apoptosis was detected through acridine orange(AO) staining and flow cytometry. Apoptotic genes were measured by RT-PCR. RESULTS: Embryo malformation was observed in the embryos exposed to S at 200 μmol·L–1. When SNO concentration was increased to 1 mmol·L–1, scoliolosis, and pericardial edema could be seen in some embryos. Results from fluorescence microscopy and flow cytometry analysis showed that S at 200 μmol·L–1 induced apoptosis, whereas the apoptotic rate in the SNO-treated group(200 μmol·L–1) was much lower than that in the S group. RT-PCR analysis showed that p53 mRNA expression and the ratio of Bax/Bcl-2 in the S group were significantly altered compared with the control group(*P < 0.05). Moreover, Bax mRNA expression in both S and SNO group were significantly different from that in the control group(**P <0.01). CONCLUSION: These results lead to the conclusion that SNO has significantly lower toxicity than S in zebrafish embryos.AIM： The application of strychnine（S） is limited due to its toxicity; strychnine N-oxide（SNO） is a derivative of strychnine. The aim was to employ zebrafish embryos to investigate and compare the developmental toxicity induced by S and SNO. METHODS： The toxicity of S and SNO was examined through the hatching rate and survival rate. Morphological changes of the zebrafish were observed with a dissecting microscope. Apoptosis was detected through acridine orange（AO） staining and flow cytometry. Apoptotic genes were measured by RT-PCR. RESULTS： Embryo malformation was observed in the embryos exposed to S at 200 μmol·L–1. When SNO concentration was increased to 1 mmol·L–1, scoliolosis, and pericardial edema could be seen in some embryos. Results from fluorescence microscopy and flow cytometry analysis showed that S at 200 μmol·L–1 induced apoptosis, whereas the apoptotic rate in the SNO-treated group（200 μmol·L–1） was much lower than that in the S group. RT-PCR analysis showed that p53 mRNA expression and the ratio of Bax/Bcl-2 in the S group were significantly altered compared with the control group（＊P 〈 0.05）. Moreover, Bax mRNA expression in both S and SNO group were significantly different from that in the control group（＊＊P 〈0.01）. CONCLUSION： These results lead to the conclusion that SNO has significantly lower toxicity than S in zebrafish embryos.

关 键 词：STRYCHNINE Strychnine N-oxide TOXICITY Zebrafish embryos APOPTOSIS 

分 类 号：R965[医药卫生—药理学]