Diabetes mellitus (DM) is associated with the development, progression and severity of periodontal disease. Since poorly controlled diabetic patients present impaired tissue healing and immuno-inflammatory response, the use of adjuvant therapies, such as host response modulators, may attend to specific therapeutic needs of this group of patients. The bisphosphonate tiludronic acid (TIL) presents anti-resorptive and anti-inflammatory effects. It has not been studied in the association periodontitis-DM so far. The purpose of this study is to immunohistochemically evaluate the effects of local administration of TIL on experimental periodontitis (EP) in rats with and without streptozotocin-induced DM. Sixty-four adult male rats (Laboratory Animal Care Facility, Ribeirao Preto School of Dentistry/University of Sao Paulo - FORP/USP) will be used. They will be randomly assigned to one of 8 experimental groups (n = 8): NDM-C, NDM-EP, NDM-EP-TIL 1, NDM-EP-TIL 3, DM-C, DM-EP, DM-EP-TIL 1 and DM-EP-TIL 3 (NDM-animals without DM, C-Control, DM-animals with DM). In the 1st day, DM will be induced in the animals of groups DM. In the 8th day, a ligature will be placed in the cervical area of right mandibular first molars of each rat, except for the rats from groups C. 20 uL TIL solutions in the dosages of 1 mg/kg body weight (for groups NDM-EP-TIL 1 and DM-EP-TIL 1) or 3 mg/kg body weight (for groups NDM-EP-TIL 3 and DM-EP-TIL 3) will be injected into the gingiva in the buccal area adjacent to right mandibular first molars every other day. Animals will be euthanized at the 18th day. Immunohistochemical analyses for TRAP, RANKL, OPG and activated caspase-3 will be performed in the periodontal tissues. Data will be statistically analyzed.
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