ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Predictive Toxicology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1593683
Organ-Specific Safety profile of Bioinspired Short Antimicrobial Peptides in Zebrafish Embryos
Provisionally accepted
Sahar Isa Daas1
Hajira Afreen2Aseela Fathima3Ahmad M Hani1Nura A Mohamed4
Md Mizanur Rahman2
Patrick G. Burgon5
Sergio Crovella6
Haissam Abou-Saleh3*- 1Department of Human Genetics, Sidra Medicine, Doha, Qatar, Doha, Qatar
- 2Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha, Qatar
- 3Department of Biomedical Sciences, College of Health Sciences, Qatar University, Doha, Qatar
- 4Biomedical Research Center, Qatar University, Doha, Qatar
- 5Department of Chemistry and Earth Sciences, College of Arts and Sciences, Qatar University, Doha, Qatar
- 6Laboratory Animal Research Center, Qatar University, Doha, Qatar
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Antimicrobial Peptides (AMPs) are vital components of the innate immune system, showcasing broad-spectrum antibacterial and immunomodulatory activities. Despite their potential as alternatives to traditional antibiotics, the optimization of their pharmacodynamic properties and safety profiles has prompted the development of Bio-inspired Short Antimicrobial Peptides (BSAMPs) through computational and bioinformatics techniques. In this study, we investigated the in vivo organ-specific safety and toxicity of two selected BSAMPs, Peptide C (GVLCCGYRCCSKWGWCGTT) and Peptide E (CWWMTRRAWR), utilizing the zebrafish model. Various phenotypic endpoints, including the Lethal Concentration (LC50), cardiotoxicity, neurotoxicity (motor neuron axons and locomotion), and hepatotoxicity assays, were assessed. The determined LC50 values for Peptide C and Peptide E were 162.2 and 131.82 μg/mL, respectively. Our findings revealed that Peptide C exhibited minimal effects on the cardiovascular system at concentrations below 150 μg/mL but demonstrated neurotoxic and hepatotoxic effects at concentrations exceeding 100 μg/mL. On the other hand, Peptide E displayed developmental toxicity at concentrations exceeding 100 μg/mL, accompanied by observed prolonged exposure effects of cardiotoxicity characterized by a decrease in heart rate, diverse locomotion outcomes, and apparent hepatotoxic effects. These results underscore the need for cautious consideration and further exploration of BSAMPs in clinical applications. The study offers significant insights into the specific impacts of BSAMPs on different organ systems utilizing the zebrafish model, contributing to understanding their safety profiles and potential therapeutic applications.
Keywords: Bioinspired Short Antimicrobial Peptides (BSAMPs), Zebrafish, developmental toxicity, Safety, Organ-specific toxicity
Received: 14 Mar 2025; Accepted: 12 May 2025.
Copyright: © 2025 Daas, Afreen, Fathima, Hani, Mohamed, Rahman, Burgon, Crovella and Abou-Saleh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Haissam Abou-Saleh, Department of Biomedical Sciences, College of Health Sciences, Qatar University, Doha, Qatar
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.