title: Toxic effects of strychnine and strychnine N-oxide on zebrafish embryos.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  These results lead to the conclusion that SNO has significantly lower toxicity than S in zebrafish embryos.
authors.affiliation: Jiangsu Key Laboratory for Chinese Medicine Processing, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China; Department of Preclinical Medicine, University of Chinese Medicine, Nanjing 210046, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Qi
authors.affiliation: Jiangsu Key Laboratory for Chinese Medicine Processing, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Yang
authors.affiliation: Jiangsu Key Laboratory for Chinese Medicine Processing, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Jiangsu Key Laboratory for Chinese Medicine Processing, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China. Electronic address: hmbian@sina.com.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Bian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000633:toxicity*; D004365:Drugs, Chinese Herbal / Q000633:toxicity*; D005260:Female; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2; D013331:Strychnine / Q000031:analogs & derivatives* / Q000633:toxicity*; D031451:Strychnos / Q000009:adverse effects / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D003497:Cyclic N-Oxides; D004365:Drugs, Chinese Herbal; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D029961:Zebrafish Proteins; C083068:strychnine N-oxide; D013331:Strychnine
keywords: Apoptosis; Strychnine; Strychnine N-oxide; Toxicity; Zebrafish embryos