A Novel Chemically Modified Curcumin Reduces Severity of Experimental Periodontal Disease in Rats: Initial Observations

Author(s)

Elburki, Muna S. ; Rossa, Carlos ; Guimaraes, Morgana R. ; Goodenough, Mark ; Lee, Hsi-Ming ; Curylofo, Fabiana A. ; Zhang, Yu ; Johnson, Francis ; Golub, Lorne M.

• Document type: Journal article
• Source: Mediators of Inflammation; v. 2014, p. 10-pg., 2014-01-01.

Abstract

Tetracycline-based matrix metalloproteinase-(MMP-) inhibitors are currently approved for two inflammatory diseases, periodontitis and rosacea. The current study addresses the therapeutic potential of a novel pleiotropic MMP-inhibitor not based on an antibiotic. To induce experimental periodontitis, endotoxin (LPS) was repeatedly injected into the gingiva of rats on one side of the maxilla; the contralateral (control) side received saline injections. Two groups of rats were treated by daily oral intubation with a chemically modified curcumin, CMC 2.24, for two weeks; the control groups received vehicle alone. After sacrifice, gingiva, blood, and maxilla were collected, the jaws were defleshed, and periodontal (alveolar) bone loss was quantified morphometrically and by mu-CT scan. The gingivae were pooled per experimental group, extracted, and analyzed for MMPs (gelatin zymography; western blot) and for cytokines (e.g., IL-1 beta; ELISA); serum and plasma samples were analyzed for cytokines and MMP-8. The LPS-induced pathologically excessive bone loss was reduced to normal levels based on either morphometric (P = 0.003) or mu-CT (P = 0.008) analysis. A similar response was seen for MMPs and cytokines in the gingiva and blood. This initial study, on a novel triketonic zinc-binding CMC, indicates potential efficacy on inflammatory mediators and alveolar bone loss in experimental periodontitis and warrants future therapeutic and pharmacokinetic investigations. (AU)

• FAPESP's process: 10/19660-2 - Biological mechanisms of curcumin-mediated modulation of osteoclastogenesis, bone resorption and repair
• Grantee: Morgana Rodrigues Guimarães Stabili
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/15826-9 - Modulation of inflammatory bone resorption by a novel chemically modified curcumin: focus on osteoclastogenesis
• Grantee: Fabiana Almeida Curylofo Zotti
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 09/54080-0 - Acquisition of an in vivo microtomography scanner for use in the Laboratory for Characterization and Evaluation of Biological Responses
• Grantee: Elcio Marcantonio Junior
• Support Opportunities: Multi-user Equipment Program