P17 The H2S-releasing naproxen-derivative ATB-346 inhibits alveolar bone loss and inflammation in rats with ligature-induced periodontitis

Abstract

Periodontitis is the result of the extension of gingival inflammation far down the periodontium, thus damaging the structures responsible for tooth-bone insertion, which may subsequently cause tooth loss. Non-steroidal antiinflammatory drugs (NSAIDs) are widely prescribed for control of a variety of inflammatory conditions, although gastric effects limit their use. In experimental periodontitis, NSAIDs also decrease the associated alveolar bone loss. Since the addition of an H2S-releasing moiety to classical NSAIDs result in antiinflammatory compounds with improved gastric safeness [1] , we decided to compare the effects of naproxen with its H2S-releasing derivative ATB-346 (Antibe Therapeutics Inc., Canada) on ligature-induced periodontitis in rats. All animal procedures were approved by the local ICB-USP Ethics Committee. A 3–0 cotton ligature was subgingivally placed around the lower right first molar of male Wistar rats (220–250 g), previously anesthetized with ketamine and xylazine (80 mg/kg and 16 mg/kg, i.p., respectively); sham animals had the ligature removed immediately after the procedure. After ligature placement, groups of animals (n = 8) started to receive daily equimolar oral bolus doses of naproxen (10 mg/kg), ATB-346 (16 mg/kg) or vehicle (1 ml/kg of 0.5% CMC) during the following 7 days; a non-treated group was also included. After this period, the anesthetized animals were euthanized (exsanguination) and the mandibles were collected, X-rayed for alveolar bone loss measurement (distance between the cemento-enamel junction and the alveolar bone crest at the mesial face of the ligatured tooth), and prepared for histological analysis. Samples of stomach and gingiva were also collected for measurement of myeloperoxidase (MPO) activity (a marker of granulocyte infiltration) and interleukin (IL)-1β contents. Data were analyzed by one-way ANOVA followed by the Student-Neuman-Keuls test. Seven days after ligature placement, both untreated or vehicle-treated animals showed similar bone loss (0.94 ± 0.06 and 0.96 ± 0.08 mm, respectively), which was significantly inhibited by either naproxen (0.74 ± 0.06 mm, P These results show that the presence of the H2S-releasing moiety in the ATB-346 compound does not impair the effects of the parent naproxen on periodontitis, but rather prevents the occurrence of deleterious effects on the gastric mucosa due to long-term prostaglandin inhibition. Financial support: CAPES, CNPq, FAPESP.