期刊
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
卷 31, 期 11, 页码 -出版社
WILEY
DOI: 10.1002/jbt.21964
关键词
acute toxicity; rhodamine B-crotamine; screening of pharmaceuticals; venom-derived peptides; zebrafish model
资金
- Macau Science and Technology Development Fund [069/2015/A2, 134/2014/A3]
- Research Committee, University of Macau [MYRG2016-00129-ICMS-QRCM, MYRG2015-00214-ICMS-QRCM, MYRG2016-00133-ICMS-QRCM]
- Program on Toxinology
- CNPq
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 4M, which effectively kill zebrafish larvae in less than 10min. With non-lethal concentrations (<1M), 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.
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