Resumo

Background: The large scale application of bacteriocins remains limited due to the lack of data regarding the cytotoxicity and immunostimulatory activity of these peptides in vivo. Bovicin HC5, a bacteriocin produced by Streptococcus bovis HC5, shows biological activity and mechanism of action similar to nisin, the most well-known bacteriocin. In order to gain insight about the safety of bovicin HC5 application, we analyzed the effects of orally administrated bovicin HC5 to BALB/c mice, focusing on the small intestine. Methods: Five-week-old female BALB/c mice were randomly divided into 3 experimental groups: negative control (NC group); mice given purified bovicin HC5 (Bov group); mice given ovalbumin (positive control, PC group; a murine model of enteropathy induced by sensitization). The mice were initially pre-sensitized with PBS, bovicin HC5 or ovalbumin, and these substances were administered for 30 days by daily gavages to the respective groups (NC, Bov or PC group). Histological and morphometric analysis were performed on tissue sections stained with hematoxylin and eosin, toluidine blue/sodium borate or with Alcian Blue/periodic acid-Schiff. The relative expression of cytokine genes was analyzed by real-time PCR. Results: The oral administration of bovicin HC5 for 58 days to BALB/c mice caused moderate edema, villous enlargement and alteration of the apical portion of the villi at the small intestine. The number of total goblet cells and PAS/AB+ cells was reduced in PC group. A hypertrophy of Paneth cells and an increase in the number of mitotic cells was observed in both Bov and PC groups. Increased number of mast cells was observed in PC group. An increase of TNF-α, INF-γ and IL-12 relative expression occurred upon administration of bovicin HC5, while increased levels of IL-5, IL-13 and IL-4 mRNA expression were detected at the PC group. Conclusion: Orally administrated bovicin HC5 caused some impairment of the small intestine (less severe than the alterations caused by ovalbumin), and stimulated the gut mucosal immunity in BALB/c mice towards significant TH1-polarized response. Considering that bovicin HC5 resisted passage in the GI tract, it might be a good candidate to be used for enteral applications. Acknowledgments: FAPEMIG, CAPES, CNPq and Propesq-UFJF.