J Periodont Res. 2018;1–9. wileyonlinelibrary.com/journal/jre | 1 © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Accepted: 4 January 2018 DOI: 10.1111/jre.12536 ORIGINAL ARTICLE Morphometric and histopathological evaluation of the effect of grape seed proanthocyanidin on alveolar bone loss in experimental diabetes and periodontitis H. Toker 1 | H. Balci Yuce 2 | A. Lektemur Alpan 1 | F. Gevrek 3 | M. Elmastas 4 1 Department of Periodontology, Faculty of Dentistry, Cumhuriyet University, Sivas, Turkey 2 Department of Periodontology, Faculty of Dentistry, Gaziosmanpaşa University, Tokat, Turkey 3 Department of Histology and Embryology, Faculty of Medicine, Gaziosmanpaşa University, Tokat, Turkey 4 Department of Chemistry, Faculty of Arts and Science, Gaziosmanpaşa University, Tokat, Turkey Correspondence Hatice Balci Yuce, Department of Periodontology, Gaziosmanpasa University Faculty of Dentistry, Tokat, Turkey. Email: htbalci@gmail.com Objective: Grape seed proanthocyanidine extract (GSPE) is a strong antioxidant de- rived from the grape seeds (Vitis vinifera, Terral J.F.) and has a polyphenolic structure with a wide range of biological activity. The aim of the present study was to evaluate the effects of GSPE on alveolar bone loss and histopathological changes in rats with diabetes mellitus and ligature-induced periodontitis. Material and Methods: Forty rats were divided into 6 study groups. Control (C, 6 rats) group, periodontitis (P, 6 rats) group, diabetes (D, 6 rats) group, diabetes and periodontitis (D+P, 6 rats) group, diabetes, periodontitis and 100 mg/kg/day GSPE (GSPE-100, 8 rats), and diabetes, periodontitis and 200 mg/kg/day GSPE (GSPE-200, 8 rats) group. Diabetes mellitus was induced by intraperitoneal injection of a single dose of streptozotocin (60 mg/kg). Periodontitis was induced via ligation method. Silk ligatures were placed at the mandibular right first molars. GSPE was administered by oral gavage. After 30 days, all rats were killed. Alveolar bone loss was measured morphometrically via a stereomicroscope. For histopathological analyses, Alizarin red staining, and matrix metalloproteinase (MMP)-8, vascular endothelial growth fac- tor and hypoxia inducible factor (HIF)-1α immunohistochemistry were performed. Tartrate-resistant acid phosphatase-positive osteoclast cells and relative total in- flammatory cells were also determined. Results: The highest alveolar bone loss was observed in the D+P group (P < .05). GSP- 200 group decreased alveolar bone loss (P < .05). The D+P group had the highest osteo- clast counts, but the difference was not significant compared to the P, GSPE-100 and GSPE- 200 groups (P > .05). The inflammation in the D+P group was also higher than the other groups (P < .05). The osteoblast numbers increased in the GSPE-100 and GSPE- 200 groups compared to the P and D+P groups (P < .05). MMP-8 and HIF- 1α levels were highest in the D+P group and GSPE significantly decreased these levels (P < .05). Conclusion: Within the limits of this animal study, it can be suggested that GSPE administration may decrease periodontal inflammation and alveolar bone loss via de- creasing MMP-8 and HIF-1α levels and increase osteoblastic activity in diabetic rats with experimental periodontitis. KEYWORDS alveolar bone loss, diabetes, grape seed proanthocyanidins, periodontitis, tartrate-resistant acid phosphatase