A number of animal studies have been conducted to investigate the host response in diabetes associated periodontitis. The rationale for these studies has been to identify biochemical markers associated with chronic progressive periodontal disease and to develop new adjunctive host modulatory therapeutic approaches, such as the use of non-antimicrobial chemically-modified tetracyclines (CMTs), to manage the long-term complications of diabetes that are not limited to periodontitis. In the current study, 30 adult Type I diabetic rats were given 15 mg/kg of CMT-8 (6a-deoxy 5-hydroxy 4-dedimethylamino tetracycline) daily, by oral gavage, for a period of 3 weeks. On day 21, blood was collected and analyzed for glycated hemoglobin; serum was analyzed for glucose, fructosamine, nitric oxide (NO) and prostaglandin E₂ (PGE₂); thioglycolate stimulated peritoneal macrophages were assayed for tumor necrosis factor-a (TNF-a) secretion. Significantly elevated diabetic blood glucose and glycated hemoglobin values (p<.001) were not affected by CMT treatment, whereas serum fructosamine, PGE₂ and NO levels were substantially lowered (p<.001) by this therapy. By scanning electron microscopy, the phenotypically different diabetic macrophages demonstrated elevated TNF-a production which was reduced to normal non-diabetic levels by systemic CMT treatment (p<.001), as measured by ELISA. We conclude that systemic administration of CMT-8 has pleiotropic effects in diabetic animals potentially reducing or preventing long-term complications of diabetes mellitus. Supported by CollaGenex Pharmaceuticals, Inc. Maria.Ryan@sunysb.edu

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