Toxic effects of strychnine and strychnine N-oxide on 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 molL-1.When SNO concentration was increased to 1 mmolL-1,scoliolosis,and pericardial edema could be seen in some embryos.Results from fluorescence microscopy and flow cytometry analysis showed that S at 200 molL-1 induced apoptosis,whereas the apoptotic rate in the SNO-treated group(200 molL-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(*P0.05).Moreover,Bax mRNA expression in both S and SNO group were significantly different from that in the control group(**P0.01).CONCLUSION:These results lead to the conclusion that SNO has significantly lower toxicity than S in zebrafish embryos.