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 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.