Preclinical studies of toxicity and safety of the AS-48 bacteriocin Cebrián, Rubén Rodríguez Cabezas, María Elena Martín-Escolano, Rubén Rubiño, Susana Garrido Barros, María Montalbán-López, Manuel Rosales Lombardo, María José Sánchez Moreno, Manuel Valdivia Martínez, Dolores Eva Martínez Bueno, Manuel Marín Sánchez, Clotilde Gálvez Peralta, Julio Juan Maqueda Abreu, Mercedes Cytotoxicity Antimicrobial peptides Topical delivery Zebrafish model Mouse model The in vitro antimicrobial potency of the bacteriocin AS-48 is well documented, but its clinical application requires investigation, as its toxicity could be 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 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 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 sensitization in mice, and the lack of toxicity in a murine model support the consideration of the broad spectrum antimicrobial peptide 2019-12-11T12:22:53Z 2019-12-11T12:22:53Z 2019-07-04 journal article Cebrián, R., Rodríguez-Cabezas, M. E., Martín-Escolano, R., Rubiño, S., Garrido-Barros, M., Montalbán-López, M., ... & Marín, C. (2019). Preclinical studies of toxicity and safety of the AS-48 bacteriocin. Journal of advanced research, 20, 129-139. http://hdl.handle.net/10481/58256 10.1016/j.jare.2019.06.003 eng http://creativecommons.org/licenses/by-nc-nd/3.0/es/ open access Atribución-NoComercial-SinDerivadas 3.0 España Elsevier BV