(CCSP009) INVESTIGATION OF CARDIOTOXICITY OF ENGINEERED ANTIMICROBIAL PEPTIDES IN ZEBRAFISH EMBRYOS

Background: Antimicrobial peptides (AMPs) are essential components of the innate immune system with broad-spectrum antibacterial and immunomodulatory activities. Despite their potential as alternatives to traditional antibiotics, natural AMPs have drawbacks such as instability and safety concerns. Engineered AMPs (EAMPs) have been developed to overcome these limitations. We have designed two EAMPs, named Pep1 (GVLCCGYRCCSKWGWCGTTK) and Pep2 (CWWMTRRAWR), that have demonstrated safety and anti-inflammatory effects on human cell lines, but their potential cardiotoxicity in vivo is unknown. This study aimed to investigate the effects of EAMPs on cardiac development and function in zebrafish embryos.

METHODS AND RESULTS: The cardiotoxicity of EAMPs was assessed by measuring heart rate and blood flow in the dorsal aorta and posterior cardinal vein of zebrafish embryos treated with a range of EAMPs concentrations (0-200 μg/mL). Zebrafish embryos treated with 100, 150, and 200 μg/mL of Pep1 showed no significant toxicity in cardiac function. However, zebrafish embryos treated with Pep2 exhibited significant cardiotoxicity, as indicated by a dose-dependent decrease in heart rate at 10, 30, and 60 μg/mL, without affecting blood flow.

Conclusion: These findings suggest that Pep1 has no significant effects on cardiovascular function, while Pep2 exhibits cardiotoxicity at moderate and higher doses. The study provides important insights into the safety and efficacy of EAMPs for future clinical applications as alternative antibiotics.