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

Abstract

AimThe 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. MethodsThe 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. ResultsEmbryo 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). ConclusionThese results lead to the conclusion that SNO has significantly lower toxicity than S in zebrafish embryos.