Efficacy of structurally diverse aldose reductase inhibitors on experimental periodontitis in rats

Background: To study aldose reductase and the sorbitol pathway in periodontitis and diabetes, rats with experimental periodontitis with or without diabetes were treated with three structurally diverse aldose reductase inhibitors (ARIs). Methods: Periodontitis was induced with three consecutive palatal injections of Porphyromonas gingivalis lipopolysaccharide (LPS) at 48-hour intervals between the first and second molars on the right side in young, age-matched, streptozotocin-induced rats with and without diabetes 44 days after initiation of diets with and without the ARIs tolrestat, imirestat, and quercetin. As an internal control, phosphate-buffered saline (PBS) was similarly injected on the left side. Twenty-four days after the final injection, all rats were euthanized. Defleshed samples were stained with 5% toluidine blue and palatal digital images were traced to include the enamel crown and exposed root. The root/enamel ratios (to estimate alveolar bone loss) were analyzed with repeated measures analysis of variance. Results: LPS injections resulted in significantly more bone loss versus PBS injections in both the rats with and without diabetes on normal diets (P <0.0001). All three ARIs significantly reduced LPS-induced periodontitis in the animals with and without diabetes (P ≤0.003) to the level where they were not different from PBS-injected sites in normal diet controls. Conclusion: All ARIs demonstrated efficacy in preventing alveolar bone loss because of periodontitis in both animals with and without diabetes, suggesting a role for the sorbitol pathway and the potential for ARIs to reduce inflammatory responses downstream from aldose reductase.