Nitric oxide synthase inhibition prevents alveolar bone resorption in experimental periodontitis in rats

Background: Periodontitis is the most frequent cause of tooth loss in adults. Nitric oxide (NO) has been linked to bone resorption mechanisms during inflammation processes. The aim of this study was to investigate the effect of NOS (NO synthase) inhibitors in the alveolar bone loss in an experimental periodontitis disease (EPD) model. Methods: Wistar rats were subjected to a ligature placement around the second upper left molars and were sacrificed at 11 days. Alveolar bone loss was evaluated by the sum of distances between the cusp tips and the alveolar bone along the axis of each molar root, subtracting from the contralateral side. Histopathological analysis was based on cell influx, alveolar bone, and cementum integrity. Leukogram was performed at 6 hours and 1, 7, and 11 days after the EPD induction. Groups were treated with the NOS inhibitors, aminoguanidine (AG) (2.5 to 10 mg/kg/d), or L-arginine methyl ester (L-NAME, 5 to 20 mg/ kg/d) intraperitoneally (i.p.), 1 hour before the EPD induction and daily for 11 days. Controls received only saline (EPD group). As controls for L-NAME specificity, groups were co-treated with either L-arginine (150 to 600 mg/kg/d) or D-arginine (600 mg/ kg/d) and L-NAME (20 mg/kg/d). Different groups were used for morphometric and histopathological analysis. Results: Both L-NAME and AG significantly and dose-dependently inhibited the alveolar bone loss as compared to EPD group. L-NAME (20 mg/kg/d) reduced the alveolar bone loss by 50%, whereas AG (5 mg/kg/d) reduced it by 47% compared to EPD. This result was coupled to a significant reduction of cell influx to the periodontium, as well as to the preservation of alveolar bone and cementum, seen at histopathology, for both compounds. The co-administration of L-arginine, but not of D-arginine reversed L-NAME effects. Conclusion: These data provide evidence that NOS inhibitors prevent inflammatory bone resorption in experimental periodontitis.