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Correlation between hemolytic activity, cytotoxicity and systemic in vivo toxicity of synthetic antimicrobial peptides.
University of Copenhagen, Denmark.
Roskilde University, Denmark; Lawrence Berkeley National Laboratory, USA.
RISE Research Institutes of Sweden.
Roskilde University, Denmark.
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2020 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 13206Article in journal (Refereed) Published
Abstract [en]

The use of non-standard toxicity models is a hurdle in the early development of antimicrobial peptides towards clinical applications. Herein we report an extensive in vitro and in vivo toxicity study of a library of 24 peptide-based antimicrobials with narrow spectrum activity towards veterinary pathogens. The haemolytic activity of the compounds was evaluated against four different species and the relative sensitivity against the compounds was highest for canine erythrocytes, intermediate for rat and human cells and lowest for bovine cells. Selected peptides were additionally evaluated against HeLa, HaCaT and HepG2 cells which showed increased stability towards the peptides. Therapeutic indexes of 50-500 suggest significant cellular selectivity in comparison to bacterial cells. Three peptides were administered to rats in intravenous acute dose toxicity studies up to 2-8 × MIC. None of the injected compounds induced any systemic toxic effects in vivo at the concentrations employed illustrating that the correlation between the different assays is not obvious. This work sheds light on the in vitro and in vivo toxicity of this class of promising compounds and provides insights into the relationship between the different toxicity models often employed in different manners to evaluate the toxicity of novel bioactive compounds in general.

Place, publisher, year, edition, pages
2020. Vol. 10, no 1, article id 13206
Keywords [en]
Drug development, Drug discovery, Drug safety, Infectious diseases, Medical research, Medicinal chemistry, Pharmacology, Toxicology
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:ri:diva-46286DOI: 10.1038/s41598-020-69995-9PubMedID: 32764602OAI: oai:DiVA.org:ri-46286DiVA, id: diva2:1458929
Available from: 2020-08-18 Created: 2020-08-18 Last updated: 2023-05-22Bibliographically approved

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Håkansson, JoakimSvenson, Johan

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