PMID- 25443369 OWN - NLM STAT- MEDLINE DCOM- 20150716 LR - 20171116 IS - 1875-5364 (Electronic) IS - 1875-5364 (Linking) VI - 12 IP - 10 DP - 2014 Oct TI - Toxic effects of strychnine and strychnine N-oxide on zebrafish embryos. PG - 760-7 LID - S1875-5364(14)60116-3 [pii] LID - 10.1016/S1875-5364(14)60116-3 [doi] AB - 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 mumol.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 mumol.L(-1) induced apoptosis, whereas the apoptotic rate in the SNO-treated group (200 mumol.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. CI - Copyright (c) 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved. FAU - Li, Yu AU - Li Y AD - 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. FAU - Qi, Xu AU - Qi X AD - Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. FAU - Yang, Yu-Wei AU - Yang YW AD - Jiangsu Key Laboratory for Chinese Medicine Processing, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China. FAU - Pan, Yang AU - Pan Y AD - Jiangsu Key Laboratory for Chinese Medicine Processing, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China. FAU - Bian, Hui-Min AU - Bian HM AD - Jiangsu Key Laboratory for Chinese Medicine Processing, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China. Electronic address: hmbian@sina.com. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141031 PL - China TA - Chin J Nat Med JT - Chinese journal of natural medicines JID - 101504416 RN - 0 (Cyclic N-Oxides) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Tumor Suppressor Protein p53) RN - 0 (Zebrafish Proteins) RN - 774C760V46 (strychnine N-oxide) RN - H9Y79VD43J (Strychnine) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Cyclic N-Oxides/*toxicity MH - Drugs, Chinese Herbal/*toxicity MH - Female MH - Male MH - Oxidative Stress/drug effects MH - Proto-Oncogene Proteins c-bcl-2 MH - Strychnine/*analogs & derivatives/*toxicity MH - Strychnos/adverse effects/*chemistry MH - Tumor Suppressor Protein p53/genetics/metabolism MH - Zebrafish/*embryology/genetics/metabolism MH - Zebrafish Proteins/genetics/metabolism OTO - NOTNLM OT - Apoptosis OT - Strychnine OT - Strychnine N-oxide OT - Toxicity OT - Zebrafish embryos EDAT- 2014/12/03 06:00 MHDA- 2015/07/17 06:00 CRDT- 2014/12/03 06:00 PHST- 2013/05/23 00:00 [received] PHST- 2014/12/03 06:00 [entrez] PHST- 2014/12/03 06:00 [pubmed] PHST- 2015/07/17 06:00 [medline] AID - S1875-5364(14)60116-3 [pii] AID - 10.1016/S1875-5364(14)60116-3 [doi] PST - ppublish SO - Chin J Nat Med. 2014 Oct;12(10):760-7. doi: 10.1016/S1875-5364(14)60116-3. Epub 2014 Oct 31.