Effect of pluronic acid F‐127 on the toxicity towards eukaryotic cells of CSA‐13, a cationic steroid analogue of antimicrobial peptides

Authors: Nagant, C.1; Savage, P.B.2; Dehaye, J.P.1

Source: Journal of Applied Microbiology, Volume 112, Number 6, 1 June 2012 , pp. 1173-1183(11)

Publisher: Wiley-Blackwell

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Aims:  CSA‐13 is an antimicrobial cationic steroid with some toxicity against eukaryotic cells. The purpose of this work was to test whether pluronic acid F‐127 could interfere with the toxicity of CSA‐13 on human umbilical vein endothelial (HUVEC) without modifying its bactericidal activity against Pseudomonas aeruginosa.

Methods and Results:  The addition of pluronic acid F‐127 slightly decreased the number of dead cells after exposure to CSA‐13. Pluronic acid F‐127 blocked the permeabilizing effect of CSA‐13 on the plasma membrane of HUVEC (uptake of ethidium bromide, release of lactate dehydrogenase) without modifying its toxic effect on their mitochondrial function (MTT test, uptake of tetramethyl rhodamine ethyl ester).

Conclusion:  Pluronic acid F‐127 decreased the toxicity of CSA‐13 against eukaryotic cells without completely protecting them from mitochondrial damage at high concentrations of the drug.

Significance and Impact of the Study:  This work establishes that studies on the toxic effects of synthetic antimicrobials on eukaryotic cells should not only focus on the permeability of the plasma membrane but also on the integrity of the mitochondria.

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1365-2672.2012.05297.x

Affiliations: 1:  Laboratoire de Chimie biologique et médicale et de Microbiologie pharmaceutique, Faculté de Pharmacie, Université libre de Bruxelles, Brussels, Belgium 2:  Department of Chemistry and Biochemistry, C100 BNSN Brigham Young University, Provo, UT, USA

Publication date: June 1, 2012

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