PMID- 28815806 OWN - NLM STAT- MEDLINE DCOM- 20180126 LR - 20180126 IS - 1099-0461 (Electronic) IS - 1095-6670 (Linking) VI - 31 IP - 11 DP - 2017 Nov TI - Evaluation in zebrafish model of the toxicity of rhodamine B-conjugated crotamine, a peptide potentially useful for diagnostics and therapeutics. LID - 10.1002/jbt.21964 [doi] AB - Crotamine is defensin-like cationic peptide from rattlesnake venom that possesses anticancer, antimicrobial, and antifungal properties. Despite these promising biological activities, toxicity is a major concern associated with the development of venom-derived peptides as therapeutic agents. In the present study, we used zebrafish as a system model to evaluate the toxicity of rhodamine B-conjugated (RhoB) crotamine derivative. The lethal toxic concentration of RhoB-crotamine was as low as 4 muM, which effectively kill zebrafish larvae in less than 10 min. With non-lethal concentrations (<1 muM), crotamine caused malformation in zebrafish embryos, delayed or completely halted hatching, adversely affected embryonic developmental programming, decreased the cardiac functions, and attenuated the swimming distance of zebrafish. The RhoB-crotamine translocated across vitelline membrane and accumulated in zebrafish yolk sac. These results demonstrate the sensitive responsivity of zebrafish to trial crotamine analogues for the development of novel therapeutic peptides with improved safety, bioavailability, and efficacy profiles. CI - (c) 2017 Wiley Periodicals, Inc. FAU - Chan, Judy Yuet-Wa AU - Chan JY AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. FAU - Zhou, Hefeng AU - Zhou H AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. FAU - Kwan, Yiu Wa AU - Kwan YW AD - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China. FAU - Chan, Shun Wan AU - Chan SW AD - State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China. FAU - Radis-Baptista, Gandhi AU - Radis-Baptista G AUID- ORCID: 0000-0001-9210-092X AD - Laboratory of Biochemistry and Biotechnology, Institute for Marine Sciences, Federal University of Ceara, Fortaleza, Brazil. FAU - Lee, Simon Ming-Yuen AU - Lee SM AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. LA - eng PT - Journal Article DEP - 20170816 PL - United States TA - J Biochem Mol Toxicol JT - Journal of biochemical and molecular toxicology JID - 9717231 RN - 0 (Crotalid Venoms) RN - 0 (Fluorescent Dyes) RN - 0 (Rhodamines) RN - E58TBP78IH (crotamine) RN - K7G5SCF8IL (rhodamine B) SB - IM MH - Animals MH - Animals, Genetically Modified MH - Crotalid Venoms/chemistry/pharmacokinetics/*toxicity MH - Embryo, Nonmammalian/drug effects MH - Fluorescent Dyes/chemistry/pharmacokinetics MH - Heart/drug effects/embryology MH - Larva/drug effects MH - Locomotion/drug effects MH - Rhodamines/*chemistry/pharmacokinetics MH - Tissue Distribution MH - Toxicity Tests/*methods MH - Zebrafish/*embryology OTO - NOTNLM OT - acute toxicity OT - rhodamine B-crotamine OT - screening of pharmaceuticals OT - venom-derived peptides OT - zebrafish model EDAT- 2017/08/18 06:00 MHDA- 2018/01/27 06:00 CRDT- 2017/08/18 06:00 PHST- 2017/05/10 00:00 [received] PHST- 2017/07/06 00:00 [revised] PHST- 2017/07/11 00:00 [accepted] PHST- 2017/08/18 06:00 [pubmed] PHST- 2018/01/27 06:00 [medline] PHST- 2017/08/18 06:00 [entrez] AID - 10.1002/jbt.21964 [doi] PST - ppublish SO - J Biochem Mol Toxicol. 2017 Nov;31(11). doi: 10.1002/jbt.21964. Epub 2017 Aug 16.