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Impact of resveratrol in risk conditions: evaluation of bone repair processess and of experimental periodontitis in diabectic and smoking rats

Grant number: 14/09480-8
Support type:Regular Research Grants
Duration: November 01, 2014 - October 31, 2016
Field of knowledge:Health Sciences - Dentistry - Periodontology
Principal researcher:Fernanda Vieira Ribeiro
Grantee:Fernanda Vieira Ribeiro
Home Institution: Vice-Reitoria de Pesquisa e Pós-Graduação. Universidade Paulista (UNIP). São Paulo , SP, Brazil
Assoc. researchers:Márcio Zaffalon Casati ; Renato Corrêa Viana Casarin


Diabetes mellitus (DM) and smoking are related to increased severity and prevalence of periodontal disease and negative effects on the bone repair. Resveratrol (resv) is a natural compound with biological effects acting in the modulation of inflammatory mediators and in events associated with bone metabolism. However, no data is available concerning the impact of resveratrol in the bone healing and in the periodontitis in the presence of DM or smoking. The present research covers 2 studies which will be carried out in parallel with the following aims: 1) determine the influence of resv in diabetic or smoking rats during the bone repair of critical-sized defects and in the bone repair around titanium implants and 2) determine the impact of resv in diabetic or smoking rats in the bone loss during experimental periodontitis. To answer the aims related to DM, 100 rats will be assigned to one of the groups: DM+RESV (n=20): induced DM + resv; DM+PLA (n=20): negative control - induced DM + placebo; DM+INS (n=20): positive control - induced DM + insulin; DM+RESV+INS (n=20): induced DM + resv + insulin; NDM (n=20): non-induced DM + placebo. DM will be induced with a single injection of streptozotocin. To answer the aims related to smoking, 60 rats will be assigned to: CS+RESV (n=20): cigarette smoke inhalation + resv; CS+PLA (n=20): cigarette smoke inhalation + placebo; NCS (n=20): non-cigarette smoke inhalation + placebo. Two calvarial defects will be created and one screw-shaped titanium implant will be inserted in each tibiae of the animals (day 0). In the day 19, periodontitis will be induced using a ligature at first mandibular and second maxillary molars. The treatments will begin at day 0 until 30 day of the experiment. One of the calvarial defects will be processed for histomorphometric analysis, and the tissue relative to the other defect will be collected for mRNA quantification of BMP-2, OPN, OPG, RANKL, Runx2, Osx, ²-catenina, Lrp-5 and Dkk1, using quantitative PCR. One of implants will be evaluated by Micro Computed Tomography and the other implant will be submitted to counter-torque analysis and gene expression of the same bone-related factors (BMP-2, OPN, OPG, RANKL, Runx2, Osx, ²-catenina, Lrp-5 and Dkk1) in the peri-implant tissue. Mandible and maxilla will be processed for morphometric analysis. The gingival tissue of mandibular molars will be collected for the quantification of IL-1², IL-4, IL-6, IL-17, INF-³ and TNF-± levels, using Luminex/MAGpix assay and the gingival tissue of maxillary molars will be submitted to gene expression analyses of OPG, RANKL, Runx2, Sost and Dkk1, using RT-PCR. The results will be compared using ANOVA ou Kruskal Wallis, after normality test, with the level of significance set at 5%. (AU)

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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CIRANO, F. R.; PIMENTEL, S. P.; CASATI, M. Z.; CORREA, M. G.; PINO, D. S.; MESSORA, M. R.; SILVA, P. H. F.; RIBEIRO, F. V.. Effect of curcumin on bone tissue in the diabetic rat: repair of peri-implant and critical-sized defects. International Journal of Oral and Maxillofacial Surgery, v. 47, n. 11, p. 1495-1503, . (14/09480-8)
PIMENTEL, SUZANA P.; CASATI, MARCIO Z.; RIBEIRO, V, FERNANDA; CORREA, MONICA GRAZIELI; FRANCK, FELIPE C.; BENATTI, BRUNO B.; CIRANO, FABIANO R.. Impact of natural curcumin on the progression of experimental periodontitis in diabetic rats. JOURNAL OF PERIODONTAL RESEARCH, . (14/09480-8)
PINO, DANILO SIQUEIRA; CASARIN, RENATO CORREA; PIMENTEL, SUZANA PERES; CIRANO, FABIANO RIBEIRO; CORREA, MONICA GRAZIELI; RIBEIRO, FERNANDA VIEIRA. Effect of Resveratrol on Critical-Sized Calvarial Defects of Diabetic Rats: Histometric and Gene Expression Analysis. JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY, v. 75, n. 12, . (14/09480-8)
RIBEIRO, FERNANDA V.; PINO, DANILO S.; FRANCK, FELIPE C.; BENATTI, BRUNO B.; TENENBAUM, HOWARD; DAVIES, JOHN E.; PIMENTEL, SUZANA P.; CASARIN, RENATO C.; CIRANO, FABIANO R.; CASATI, MARCIO Z.. Resveratrol Inhibits Periodontitis-Related Bone Loss in Rats Subjected to Cigarette Smoke Inhalation. Journal of Periodontology, v. 88, n. 8, p. 788-798, . (14/09480-8)
LAMEIRA, JR., ALADIM GOMES; FRANCOSO, BEATRIZ GANHITO; ABSY, SAMIR; PECORARI, VANESSA GALEGO; CASATI, MARCIO ZAFALON; RIBEIRO, FERNANDA VIEIRA; ANDIA, DENISE CARLETO. Resveratrol Reverts Epigenetic and Transcription Changes Caused by Smoke Inhalation on Bone-Related Genes in Rats. DNA AND CELL BIOLOGY, v. 37, n. 8, p. 670-679, . (14/09480-8, 13/09650-8)

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