Effect of an aldose reductase inhibitor on alveolar bone loss associated with periodontitis in diabetic rats.

Periodontitis is a lesser known but frequent complication of diabetes mellitus and is the major cause of tooth loss in patients with diabetes. Dental therapy for this complication is primarily focused on the control of oral infections. No current therapy directly addresses the potential effects of diabetes itself on this complication. In studies conducted in young normal control and streptozotocin diabetic rats (100 g) treated with and without the aldose reductase inhibitor (ARI) imirestat, experimental periodontitis was induced in one side of the mouth by 3 injections of lipopolysaccharide (LPS) from Escherichia coli 055:B5 9 into the palatal gingiva between the first and second maxillary molars at 48-hour intervals. The other control side was injected with phosphate buffered saline (PBS). Fourteen days after the final injection, all rats were euthanized and the heads were defleshed. The maxillary area was separated from the remaining skull. The cleaned maxillary alveoli were stained in 5% aqueous toluidine blue to identify the cemento-enamel junction (CEJ) on the molars. Alveolar bone loss was measured according to standard methods by determining both the distance between the CEJ and the alveolar bone on the 2 molars between which the injections were made, and by measuring the ratio of root area/enamel area in the same region. These measurements showed that LPS injections resulted in significant bone loss compared with PBS injections in both control and diabetic rats, and that this bone loss was not present in the ARI-treated diabetic rats (P < 0.05). These results suggest that the sorbitol pathway plays a critical role in the pathophysiological mechanism(s) of diabetic periodontitis and that AR may be a direct pharmacological target for the treatment for this disease.