RESUMO
BACKGROUND: This study evaluated the effects of the probiotic Bifidobacterium animalis subsp. lactis HN019 (HN019) in the development of experimental periodontitis (EP) in rats submitted to chemotherapy (5-fluorouracil [5FU]). METHODS: Eighty male rats were divided into the following groups: control (C); treated with 5FU (60 mg/kg at day 30 and 40 mg/kg at day 32); treated with probiotic (HN019) (daily, for 44 days, starting at day 0); treatment with 5FU and probiotic (5FU-HN019); only EP (EP) (ligature placed on lower first molars at day 30, maintained for 14 days); EP and treatment with 5FU (EP-5FU); EP and treatment with probiotic (EP-HN019); and EP and treatment with 5FU and probiotic (EP-5FU-HN019). Euthanasia occurred at day 44. Morphometric, histomorphometric, microtomographic, immunohistochemical, immunoenzymatic, and gene expressions analyses were performed. The data obtained were statistically analyzed (p < 0.05). RESULTS: The EP-5FU-HN019 group showed less bone and connective tissue loss when compared with EP-5FU group, while EP-HN019 and EP-5FU-HN019 groups had greater bone volume than EP and EP-5FU groups, respectively (p < 0.05). A decrease in immunostaining for tartrate-resistant acid phosphatase and RANKL, an increase for osteoprotegerin and lower interleukin-1ß levels were observed in EP-5FU-HN019 group, when compared with EP-5FU group (p < 0.0001). Probiotic therapy led to an increase in the proportions of B. lactis in the feces (p = 0.0018), but not in the biofilm, and reduced the expression of Fusobacterium nucleatum and Prevotella intermedia in the biofilm (p < 0.0001). CONCLUSION: B. lactis HN019 reduced the severity of EP in rats submitted to chemotherapy, modulating immunoinflammatory parameters in periodontal tissues and reducing periodontopathogens expression on biofilm in rats submitted to chemotherapy.
Assuntos
Bifidobacterium animalis , Periodontite , Probióticos , Ratos , Masculino , Animais , Periodontite/microbiologia , Terapia de Imunossupressão , Probióticos/farmacologia , Probióticos/uso terapêutico , Fluoruracila/uso terapêuticoRESUMO
BACKGROUND: Periodontal pathogenesis takes into consideration that disease results from a complex inflammatory immune response. Among the major cytokines related to periodontal damage, interleukin (IL)-6 enhances a cascade of tissue destruction. Tocilizumab (TCZ) is a humanized monoclonal anti-human IL-6 receptor that inhibits IL-6-mediated proinflammatory activity. This study aimed to elucidate whether TCZ inhibits the deleterious effect of ligature-induced periodontitis. METHODS: Experimental ligature-induced periodontitis was treated with systemic administration of TCZ intraperitoneally in three different concentration dosages (2 mg/kg, 4 mg/kg, and 8 mg/kg. Euthanasia occurred at 7 and 14 days after the initiation of the study. Local changes in the alveolar bone were measured by bone volume, the ratio of bone volume, and trabecular thickness using microcomputed tomography. Attachment loss and inflammatory infiltrate were evaluated by histology. Immune response was analyzed focusing on the Th17 pattern. RESULTS: TCZ inhibited alveolar bone resorption and attachment loss in 7 and 14 days for all dosage groups in comparison to controls (P < 0.05). Besides, TCZ induced lower expression of inflammatory infiltrate (P <0.05) and less production of Th17-related cytokines (P <0.05) and RANKL (P <0.05). CONCLUSIONS: The inhibition of IL-6-mediated proinflammatory activity by IL-6R blocking reduced alveolar bone resorption and attachment loss supported by the modulation of the Th17 periodontal response. Considering the inflammatory status, modulatory therapy may be a promising approach to periodontal disease.