RESUMO
Oral mucositis (OM) is a common adverse effect resulting from cancer therapy. The OM it has implications that may compromise oncologic treatment and decrease the patient's quality of life. The therapeutic options to prevent or treat the symptoms of OM are scarce; there is no effective therapy that improves the symptoms. Based on the need for further research for the treatment of OM, the present study objective was to evaluate the effect of telmisartan (TELM) on the OM induced by 5-fluorouracil (5-FU), using as animal model Golden Syrian hamsters. 5-FU followed by mechanical trauma on day 4 was used to induce OM in hamsters. Euthanasia occurred on the day 10. The experiments were constituted by the groups saline, mechanical trauma, 5-FU, and TELM in three doses (1, 5, or 10 mg/kg). Macroscopic, histopathological, and immunohistochemical analyses as well as immunofluorescence experiments were performed on the oral mucosa of the animals. The samples also were used for analysis enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reactions (qPCR). TELM (5 or 10 mg/kg) was able to reduce the inflammatory ulceration and infiltration in the oral mucosa of the animals, decreasing the levels of the cytokines TNF-α and IL-1ß. These treatments was minimize the immunostaining for cyclooxygenase-2, matrix metalloproteinase-9, transforming growth factor-ß, and smad 2/3. The nuclear transcription factor kappa B (NFκB) p65 and inducible nitric oxide synthase were reduced in the oral mucosa. Finally, TELM (10 mg/kg) increased the PPARγ gene expression and reduced STAT1 and NFκB p65 gene expression relative to the 5-FU group. Therefore, TELM prevents the OM produced by 5-FU on animal model.
RESUMO
Periodontitis is a chronic inflammatory disease related to tooth loss in adults. Infliximab is a chimeric monoclonal antibody against TNF-α and is prescribed for the treatment of systemic inflammatory diseases. This study aimed to investigate the role of infliximab on experimental periodontal disease (EPD). EPD was induced by passing a 3.0 nylon thread around the upper left second molar in Wistar rats. Animals were either treated with intravenous infliximab (1, 5, 7, and 10 mg/kg) or saline solution 30 min before the periodontitis induction and were followed until they were sacrificed on the 11th day. A subset of rats was euthanized on the third day for analysis of gingival myeloperoxidase (MPO) and the blood MPO granulocyte index. In addition, we analyzed the bone loss index (BLI), the periodontal histopathological score, and the periodontal collagen network using confocal microscopy. We also analyzed metalloproteinase-1/-8, RANK, RANK-L, and osteoprotegerin in maxillary tissue by immunohistochemistry Gingival MPO, IL-1ß, TNF-α were measured by ELISA. EPD caused leukocytosis, significant increases in BLI and gingival pro-inflammatory cytokines and cell infiltrates, with worse histopathological scores and periodontal collagen derangement. Infliximab (5 mg/kg) reduced granulocyte blood counts, gingival IL-1ß, TNF-α, and MPO levels, diminished MMP-1/-8, RANK, and RANK-L bone immunolabeling with better periodontal histopathological scores and collagen network in comparison with the challenged saline group. We concluded that infliximab had significant anti-inflammatory and bone-protective effects in Wistar rats challenged by periodontitis.