ABSTRACT
OBJECTIVE: Grape seed proanthocyanidine extract (GSPE) is a strong antioxidant derived 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 factor and hypoxia inducible factor (HIF)-1α immunohistochemistry were performed. Tartrate-resistant acid phosphatase-positive osteoclast cells and relative total inflammatory 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 osteoclast 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 decreasing MMP-8 and HIF-1α levels and increase osteoblastic activity in diabetic rats with experimental periodontitis.
Subject(s)
Alveolar Bone Loss/drug therapy , Alveolar Bone Loss/pathology , Diabetes Mellitus, Experimental/complications , Grape Seed Extract/pharmacology , Grape Seed Extract/therapeutic use , Periodontitis/drug therapy , Periodontitis/pathology , Proanthocyanidins/pharmacology , Proanthocyanidins/therapeutic use , Alveolar Bone Loss/classification , Alveolar Process/pathology , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Blood Glucose/analysis , Body Weight , Disease Models, Animal , Grape Seed Extract/administration & dosage , Hypoxia-Inducible Factor 1/analysis , Immunohistochemistry , Inflammation/drug therapy , Inflammation/pathology , Injections, Intraperitoneal , Ligation/adverse effects , Male , Matrix Metalloproteinase 8/analysis , Osteoblasts/drug effects , Osteoblasts/pathology , Osteoclasts/drug effects , Osteoclasts/pathology , Proanthocyanidins/administration & dosage , Rats , Rats, Wistar , Streptozocin/administration & dosage , Streptozocin/pharmacology , Tartrate-Resistant Acid Phosphatase/analysis , Vascular Endothelial Growth Factor A/analysisABSTRACT
The aims of our study were to assess whether the increased oxidative stress in experimental otitis media with effusion (OME) induced by histamine was reflected erythrocytes and middle ear effusion fluid by lipid peroxidation; to survey the alterations in antioxidant enzyme activities in experimental OME; and to determine the effect of dantrolene on this oxidative stress. Erythrocyte and middle ear effusion malondialdehyde (MDA) level, erythrocyte glutathione (GSH) and glutathione peroxidase (GSH-Px), glutathione reductase (GRD) and glutathione-S-transferase (GST) activities were measured in three groups of seven guinea pigs, 3 hours after injection of 0.1 mL of histamine (or saline) into the middle ear in guinea pigs with OME (experimental group), in a dantrolene sodium group and in a control group. Erythrocyte and effusion MDA levels in the dantrolene group were significantly lower than those of the experimental group. Erythrocyte GSH-Px, GST, GRD activities, and GSH levels were significantly higher in the dantrolene group than in the experimental group. Dantrolene sodium decreased the erythrocyte and effusion MDA levels, on the other hand, it increased the GSH and GSH-dependent enzymes. These findings suggest that reactive oxygen species (ROS) play a role in histamine-induced OME. Pre-treatment with dantrolene sodium increases antioxidant enzymes activities and decreases formation of MDA, the indicator of lipid peroxidation, in histamine-induced OME.
