title: Safety evaluation of the antimicrobial peptide bovicin HC5 orally administered to a murine model.
abstract: BACKGROUND
  Bovicin HC5 is an antimicrobial peptide that shows a broad spectrum of activity and potential for biotechnological and therapeutic applications. To gain insight about the safety of bovicin HC5 application, the histological and immunostimulatory effects of orally administrated bovicin HC5 to BALB/c mice were evaluated. BALB/c mice were divided into three groups: negative control (NC group); mice given purified bovicin HC5 (Bov group); mice given ovalbumin (positive control, PC group; a murine model of enteropathy). The mice were initially pre-sensitized, and PBS, bovicin HC5 or ovalbumin were administered for 30 days by daily gavages. Histological and morphometric analysis were performed and the relative expression of cytokines was analyzed by real-time RT-PCR.
  
  
  RESULTS
  The oral administration of bovicin HC5 to BALB/c mice reduced weight gain and caused alterations in the small intestine, although absorptive changes have not been detected. The number of total goblet cells and the mucopolysaccharides production were not affected by bovicin HC5 administration. A hypertrophy of Paneth cells and an increase in the number of mitotic cells were observed in Bov group, while the number of mast cells remained unaltered. Increased expression of TNF-α, INF-γ and IL-12 was observed in the small intestine upon bovicin HC5 administration.
  
  
  CONCLUSIONS
  Bovicin HC5 has only minor effects on intestinal permeability and did not elicit an allergenic response upon oral administration to animal models. Considering the low in vivo toxicity of bovicin HC5, it might be a good candidate for enteral applications.
authors.forename: Aline Dias
authors.initials: AD
authors.lastname: Paiva
authors.forename: Kenner Morais
authors.initials: KM
authors.lastname: Fernandes
authors.forename: Roberto Sousa
authors.initials: RS
authors.lastname: Dias
authors.forename: Alípio dos Santos
authors.initials: Ados S
authors.lastname: Rocha
authors.forename: Leandro Licursi de
authors.initials: LL
authors.lastname: Oliveira
authors.forename: Clóvis Andrade
authors.initials: CA
authors.lastname: Neves
authors.forename: Sérgio Oliveira de
authors.initials: SO
authors.lastname: Paula
authors.forename: Hilário Cuquetto
authors.initials: HC
authors.lastname: Mantovani
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001430:Bacteriocins / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006025:Glycosaminoglycans / Q000096:biosynthesis; D020397:Goblet Cells / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000033:anatomy & histology / Q000187:drug effects*; D008407:Mast Cells / Q000187:drug effects; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015430:Weight Gain
chemical_list: D001430:Bacteriocins; D006025:Glycosaminoglycans; D014409:Tumor Necrosis Factor-alpha; C514465:bovicin HC5, Streptococcus bovis HC5; D018664:Interleukin-12; D007371:Interferon-gamma
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