Toxicity Evaluation to Mice of Phylloseptin-1, an Antimicrobial Peptide from the Skin Secretion of Phyllomedusa hypochondrialis (Amphibia)

The growing resistance of microorganisms to antibiotics has been considered as a global public health problem. Therefore, the search for novel antimicrobial drugs, chemically unrelated to the presently used antibiotics, is urgently needed. Our group has recently characterized a new family of antimicrobial peptides – phylloseptins – isolated from the skin secretion of the South American amphibian Phyllomedusa hypochondrialis, which showed a strong antimicrobial effect against Gram-positive and Gram-negative bacteria. We now investigate the in vivo toxicity of synthetic phylloseptin-1 (PS-1) toward bone marrow, liver, spleen, kidney and lung after endovenous administration to Swiss mice of a bolus dose of 4 mg/kg. Genotoxicity was evaluated by quantifying erythrocyte micronuclei. PS-1-treated mice showed no alteration in the histology of liver, spleen, kidney and lung, as well as of blood biochemistry, as compared to normal controls. Cytotoxicity tests, evaluated either by blood cytometry or bone marrow polychromatophilic erythrocyte index, revealed no deleterious effect of PS-1. Moreover, the peptide showed no toxicity towards bone marrow erythrocytes. We concluded that, in a concentration ten times over that providing antimicrobial effect, synthetic PS-1 showed no in vivo toxicity.