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| Author(s): |
Bruno Schneider Herrera
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2008-08-07 |
| Examining board members: |
Marcelo Nicolas Muscara;
Edson Antunes;
Jarbas Arruda Bauer;
Francisco Humberto Nociti Junior;
Sandra Helena Penha de Oliveira
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| Advisor: | Marcelo Nicolas Muscara |
| Abstract | |
The periodontal disease is the most prevalent chronic disease in oral diseases. Among the mediators of this process, is the Resolvin E1 (RvE1), a novel mediator pro-resolving of inflammation that is capable to decrease alveolar bone loss secondary to periodontal disease in rabbits; and the nitric oxide (NO), that can be produced in large amount, induced by cytokines and it can stimulate the osteoclast differentiation and activity. The aim of this study is to investigate the effects of RvE1 on osteoclasts (OCs) culture and the pathway involved, also the role of NO in the progression of experimental periodontitis in rats and systemic alterations due to oxidative damage. The OCs differentiation was induced in bone marrow cell culture from C57BL/6 mice (7 days) and treated with various doses of RvE1. NF<font face=\"symbol\">kB and Akt phosphorylation were analyzed with Western blotting and the genic expression of NO synthase (NOS) inducible (iNOS) with \"Real Time\" PCR. The role of receptors ChemR23 and BLT-1 was accessed in OCs isolated membranes performing radioligants. The alveolar bone loss and peripheral organ damage was assessed in rats with ligature-induced periodontitis (P) under a long-term treatment of a NOS inhibitor, L-NAME. The animals received L-NAME from two weeks prior to periodontitis induction and until their sacrifice (3, 7 and 14 days after ligature). The alveolar bone loss was evaluated radiographically, and the protein nitrotyrosine (NT) content, reactive species of thiobarbituric acid (TBARs) and myeloperoxidase activity (MPO) were analyzed in samples of heart, spleen, kidney, lungs and kidneys. RvE1 (3 ng/mL) trough BLT-1 receptor activation (but not ChemR23) inhibits the OCs differentiation and activity (p<0.05) after 5 or 7 days of the culture, as well as the Akt phosphorylation and NF-<font face=\"symbol\">kB translocation to the nucleus, a key event both in OCs differentiation (p<0.05) and iNOS expression decreases. In vivo, P rats (day 7) show an increase of heart NT and renal MPO, but lower lung MPO activity in comparison to the Sham group (S; p<0.05). L-NAME leads to an increase the liver NT expression in P rats on day 3 (p<0.05), but decreases the cardiac NT on day 7 (p<0.01). In comparison with the P group, P+LN rats showed significantly increased liver, heart and kidney MPO content on day 3 (p<0.05), but lower lung MPO (day 7) and spleen TBARs (day 3) content (p<0.05). In summary we have shown that RvE1 binding on BLT-1 receptor inhibits OCs differentiation and activity by interfering with Akt and NF-<font face=\"symbol\">kB signaling and consequently iNOS inhibition, and NO has a central role on periodontitis, not only related to the local consequences on alveolar bone resorption, but also on distant peripheral organs. (AU) | |