Abstract | BACKGROUND: METHODS: Adult male rats received intragingival injections with either 10 microl of physiologic saline or Escherichia coli endotoxin (1 mg/ml) every other day for 6 days and were distributed into 8 treatment groups (12 rats/group): saline (S), endotoxin alone (E), E + CMT-1, E + CMT-3, E + CMT-4, E + CMT-7, E + CMT-8, and doxycycline. All animals were treated daily with 1 ml of 2% carboxymethyl cellulose (CMC) alone or containing one of the above-mentioned CMTs (2 mg/day) orally. The gingival tissues were removed, extracted, and assayed for gelatinase ( GLSE). Some rat maxillary jaws from each treatment group were fixed in buffered formalin and processed for histology and immunohistochemistry for the cytokines tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6, and MMP-2 and MMP-9. RESULTS:
Endotoxin injection induced elevated GLSE activity (functional assay and osteoclast-mediated bone resorption), the former identified as predominantly MMP-9 (92 kDa GLSE) by gelatin zymography. All 6 tetracyclines (2 mg/day) inhibited periodontal breakdown in the following order of efficacy: CMT-8 > CMT- 1 > CMT-3 > doxycycline > CMT-4 > CMT-7. Immunohistochemistry was positive for TNF, IL-1, and IL-6 in the inflammatory cells from untreated endotoxin rat tissues, whereas treatment with CMTs decreased the number of immuno-positive stained cells for cytokines and MMPs. The in vivo efficacy of these drugs varied with CMT structure and was significantly correlated with bone resorption: r2 = -0.77, P<0.01; gelatinase inhibitory activity: r2 = -0.84, P <0.01; and serum drug concentrations. CONCLUSION: Since both conventional (antimicrobial) and non-antimicrobial tetracyclines inhibited periodontal bone resorption induced by endotoxin injection, MMP-mediated bone loss in this model can be prevented by inhibition of MMPs.
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Authors | Nungavarum S Ramamurthy, Barry R Rifkin, Robert A Greenwald, Jing-Wen Xu, Yu Liu, Gloria Turner, Lorne M Golub, Anthony T Vernillo |
Journal | Journal of periodontology
(J Periodontol)
Vol. 73
Issue 7
Pg. 726-34
(Jul 2002)
ISSN: 0022-3492 [Print] United States |
PMID | 12146531
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Anti-Bacterial Agents
- Endotoxins
- Interleukins
- Protease Inhibitors
- Tetracyclines
- Tumor Necrosis Factor-alpha
- Gelatinases
- Doxycycline
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Topics |
- Alveolar Bone Loss
(chemically induced, drug therapy, enzymology)
- Analysis of Variance
- Animals
- Anti-Bacterial Agents
(pharmacology, therapeutic use)
- Disease Models, Animal
- Doxycycline
(pharmacology, therapeutic use)
- Electrophoresis, Polyacrylamide Gel
- Endotoxins
- Gelatinases
(antagonists & inhibitors)
- Immunoenzyme Techniques
- Interleukins
(analysis)
- Male
- Periodontitis
(chemically induced, drug therapy, enzymology)
- Protease Inhibitors
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Tetracyclines
(pharmacology, therapeutic use)
- Tumor Necrosis Factor-alpha
(analysis)
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