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Tetracyclines inhibit connective tissue breakdown: new therapeutic implications for an old family of drugs.
- Source :
-
Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists [Crit Rev Oral Biol Med] 1991; Vol. 2 (3), pp. 297-321. - Publication Year :
- 1991
-
Abstract
- Tetracyclines have long been considered useful adjuncts in peridontal therapy based on their antimicrobial efficacy against putative periodontopathogens. However, recently these drugs were found to inhibit mammalian collagenases and several other matrix metalloproteinases (MMPs) by a mechanism independent of their antimicrobial activity. Evidence is presented that this property may be therapeutically useful in retarding pathologic connective tissue breakdown, including bone resorption. The experiments leading to this discovery are described and possible mechanisms are addressed, including the specificity of tetracyclines' anti-collagenase activity, the role of the drugs' metal ion (Zn2+, Ca2+)-binding capacity, and the site on the tetracycline molecule responsible for this nonantimicrobial property. Of extreme interest, the tetracycline molecule has been chemically modified in multiple ways, generating a new family of compounds called CMTs (chemically modified tetracyclines) that lack antimicrobial but still retain anti-collagenase activity. The first of these CMTs, 4-de-di-methylaminotetracycline, was found not to produce a major side-effect of antimicrobial tetracycline therapy--its administration to experimental animals did not result in the emergence of tetracycline-resistant microorganisms in the oral flora and gut. Numerous examples of the clinical potential of this non-antimicrobial property of tetracyclines in the treatment of periodontal and several medical diseases (e.g., sterile corneal ulcers, rheumatoid arthritis, skin bullous lesions, tumor-induced angiogenesis and metastasis) are discussed.
- Subjects :
- Animals
Connective Tissue drug effects
Connective Tissue enzymology
Humans
Microbial Collagenase chemistry
Periodontal Diseases drug therapy
Periodontal Diseases enzymology
Tetracyclines chemistry
Tetracyclines therapeutic use
Microbial Collagenase antagonists & inhibitors
Tetracyclines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1045-4411
- Volume :
- 2
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists
- Publication Type :
- Academic Journal
- Accession number :
- 1654139
- Full Text :
- https://doi.org/10.1177/10454411910020030201