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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Soluble epoxide hydrolase inhibitor promotes immunomodulation to inhibit bone resorption

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Napimoga, M. H. [1] ; Rocha, E. P. [1] ; Trindade-da-Silva, C. A. [2, 3] ; Demasi, A. P. D. [1] ; Martinez, E. F. [1] ; Macedo, C. G. [1] ; Abdalla, H. B. [4] ; Bettaieb, A. [5] ; Haj, F. G. [6] ; Clemente-Napimoga, J. T. [1] ; Inceoglu, B. [2, 3] ; Hammock, B. D. [2, 3]
Total Authors: 12
[1] Sao Leopoldo Mandic Inst & Res Ctr, Campinas, SP - Brazil
[2] Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 - USA
[3] Univ Calif Davis, UC Davis Comprehens Canc Ctr, Davis, CA 95616 - USA
[4] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Physiol, Lab Orofacial Pain, Piracicaba, SP - Brazil
[5] Univ Tennessee, Dept Nutr, Knoxville, TN 37996 - USA
[6] Univ Calif Davis, Dept Nutr, Davis, CA 95616 - USA
Total Affiliations: 6
Document type: Journal article
Source: JOURNAL OF PERIODONTAL RESEARCH; v. 53, n. 5, p. 743-749, OCT 2018.
Web of Science Citations: 1

Background and ObjectiveSoluble epoxide hydrolase (sEH) is an enzyme in the arachidonate cascade which converts epoxy fatty acids (EpFAs), such as epoxyeicosatrienoic acids (EETs) produced by cytochrome P450 enzymes, to dihydroxy-eicosatrienoic acids. In the last 20 years with the development of inhibitors to sEH it has been possible to increase the levels of EETs and other EpFAs in in vivo models. Recently, studies have shown that EETs play a key role in blocking inflammation in a bone resorption process, but the mechanism is not clear. In the current study we used the sEH inhibitor (1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea {[}TPPU]) to investigate the immunomodulatory effects in a mouse periodontitis model. Material and MethodsMice were infected on days 0, 2, and 4 with Aggregatibacter actinomycetemcomitans and divided into groups (n=6) that were treated orally, daily for 15days, with 1mg/kg of TPPU. Then, the mice were killed and their jaws were analyzed for bone resorption using morphometry. Immunoinflammatory markers in the gingival tissue were analyzed by microarray PCR or western blotting. ResultsInfected mice treated with TPPU showed lower bone resorption than infected mice without treatment. Interestingly, infected mice showed increased expression of sEH; however, mice treated with TPPU had a reduction in expression of sEH. Besides, several proinflammatory cytokines and molecular markers were downregulated in the gingival tissue in the group treated with 1mg/kg of TPPU. ConclusionThe sEH inhibitor, TPPU, showed immunomodulatory effects, decreasing bone resorption and inflammatory responses in a bone resorption mouse model. (AU)

Grantee:Marcelo Henrique Napimoga
Support type: Regular Research Grants