Preclinical studies of toxicity and safety of the AS-48 bacteriocin

Publication date: Available online 4 July 2019Source: Journal of Advanced ResearchAuthor(s): Rubén Cebrián, M. Elena Rodríguez-Cabezas, Rubén Martín-Escolano, Susana Rubiño, María Garrido-Barros, Manuel Montalbán-López, María José Rosales, Manuel Sánchez-Moreno, Eva Valdivia, Manuel Martínez-Bueno, Clotilde Marín, Julio Galvez, Mercedes MaquedaAbstractThe in vitro antimicrobial potency of the bacteriocin AS-48 is well documented, but its clinical application requires investigation, as its toxicity is different in in vitro (haemolytic and antibacterial activity in blood and cytotoxicity towards normal human cell lines) and in vivo (e.g. mice and zebrafish embryos) models. Overall, the results obtained are promising. They reveal the negligible propensity of AS-48 to cause cell death or impede cell growth at therapeutic concentrations (up to 27 μM) and support the suitability of this peptide as a potential therapeutic agent against several microbial infections, due to its selectivity and potency at low concentrations (in the range of 0.3–8.9 μM). In addition, AS-48 exhibits low haemolytic activity in whole blood and does not induce nitrite accumulation in non-stimulated RAW macrophages, indicating a lack of pro-inflammatory effects. The unexpected heightened sensitivity of zebrafish embryos to AS-48 could be due to the low differentiation state of these cells. The low cytotoxicity of AS-48, the absence of lymphocyte proliferation in vivo after skin sensitizatio...

Source: Journal of Advanced Research - July 5, 2019 Category: Research Source Type: research