Preclinical studies of toxicity and safety of the AS-48 bacteriocin
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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, MercedesEditorial
Elsevier BV
Materia
Cytotoxicity Antimicrobial peptides Topical delivery Zebrafish model Mouse model
Fecha
2019-07-04Referencia bibliográfica
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.
Patrocinador
This research was funded by the Spanish Ministry of Economy and Competitiveness (SAF2013-48971-C2-1-R, CSD2010-00065, and AGL2015-67995-C3-3-R, all including funds from the European Regional Development Funding, ERDF) and by the Research Groups (BIO160, CTS 944 and CTS 164, UGR) from Junta de Andalucía (Spain). The CIBER-EHD is funded by the Instituto de Salud Carlos III. RM-E is grateful for an FPU Grant (FPU14/01537) from the Ministry of Education, (Spain).Resumen
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