Minocycline reduces gingival collagenolytic activity during diabetes

Autor: A. Nemiroff, N. S. Ramamurthy, G. Lehrer, Hsi-Ming Lee, R. Kaplan, L. M. Golub, Thomas F. Mcnamara
Rok vydání: 1983
Předmět:
Zdroj: Journal of Periodontal Research. 18:516-526
ISSN: 1600-0765
0022-3484
DOI: 10.1111/j.1600-0765.1983.tb00388.x
Popis: Diabetes increases gingival collagenase activity, an effect that may be mediated by endogenous tissue changes and exacerbated by an overgrowth of Gram-negative organisms in the gingival crevice (see Ramamurthy & Golub 1983, McNamara et al. 1982). In an attempt to reverse this collagenolytic abnormality, we administered an appropriate antibiotic, minocycline (a semisynthetic tetracycline), to diabetic rats and humans. Adult male conventional or germfree rats were made diabetic with streptozotocin, and half of these animals were administered minocycline (20 mg per day) by tube feeding for 3–4 weeks prior to sacrifice. The buccal gingiva, entire skins, and mandibles were dissected and tested for collagenolytic enzyme activity, collagen content, and alveolar bone loss, espectively. In a preliminary study, minocycline (200 mg per day) was administered for 7 days to an insulin-dependent diabetic adolescent human and an adult non-diabetic human; the twin brother of the diabetic was treated with penicillin. Gingival fluid collagenase activity was measured (using [3H-methyl] collagen as substrate in a new microassay) in 8 periodontal pockets in each subject before and after antibiotic therapy. Examination of collagenase digestion products by SDS-polyacrylamide gel electrophoresis and fluorography was also carried out. In rats, minocycline treatment: (1) suppressed the abnormally elevated collagenolytic enzyme activity in gingiva of diabetic rats, even under germfree conditions; (2) inhibited PMN leukocyte collagenase activity in vitro, an effect that was reversed by the addition of calcium ions (penicillin-streptomycin had no effect on the activity of this enzyme); and (3) retarded the abnormal loss of skin collagen and alveolar bone in diabetic rats. In a preliminary study on humans, minocycline therapy reduced the collagenase activity of gingival crevicular fluid, an effect not produced by penicillin. Our data suggests that (1) tetracycline therapy inhibits tissue collagenolytic enzyme activity by a mechanism al least in part unrelated to its antibacterial efficacy, and (2) this mechanism may provide a new therapeutic approach for suppressing excessive collagen resorption which occurs during periodontal disease and which can occur during other pathologic conditions.
Databáze: OpenAIRE
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