Elburki, Muna S.Rossa, Carlos [UNESP]Guimaraes, Morgana R. [UNESP]Goodenough, MarkLee, Hsi-MingCurylofo, Fabiana A. [UNESP]Zhang, YuJohnson, FrancisGolub, Lorne M.2014-12-032014-12-032014-01-01Mediators Of Inflammation. New York: Hindawi Publishing Corporation, 10 p., 2014.0962-9351http://hdl.handle.net/11449/112505Tetracycline-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.10engArtigo10.1155/2014/959471WOS:000338870200001Acesso abertoWOS000338870200001.pdf