Rutin alleviates bisphenol A-glycidyl methacrylate-induced generation of proinflammatory mediators through the MAPK and NF-κB pathways in macrophages

Bisphenol A-glycidyl methacrylate (BisGMA) is a methacrylate monomer that is mainly used in three-dimensional structures to reconstruct dental and bony defects. BisGMA has toxic and proinflammatory effects on macrophages. Rutin is a natural flavonol glycoside that is present in various plants and has useful biological effects, such as anti-inflammatory, anticancer, and antioxidative effects. The aim of this study was to investigate the anti-inflammation of rutin in macrophages after exposure to BisGMA. Pretreatment of the RAW264.7 macrophage with rutin at 0, 10, 30, and 100 mu M for 30 min before being incubated with BisGMA at 0 or 3 mu M. Proinflammatory cytokines and prostaglandin (PG) E2 were detected by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) was detected by the Griess assay. Expression and phosphorylation of proteins were measured by Western blot assay. Pretreatment with rutin inhibited the BisGMA-induced generation of proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, and PGE2, in macrophages. Rutin also suppressed the BisGMA-induced secretion of NO and expression of inducible nitric oxide synthase (iNOS) in a concentration-dependent manner. Furthermore, rutin suppressed the mitogen-activated protein kinase (MAPK) phosphorylation in a concentration-dependent manner. Finally, rutin suppressed the BisGMA-induced phosphorylation of nuclear factor (NF)-kappa B p65 and degradation of inhibitor of kappa B (I kappa B). These results indicate that the concentration of rutin has an inhibitory effect on proinflammatory mediator generation, MAPK phosphorylation, NF-kappa B p65 phosphorylation, and I kappa B degradation. In conclusion, rutin is a potential anti-inflammatory agent for BisGMA-stimulated macrophages through NF-kappa B p65 phosphorylation and I kappa B degradation resulting from MAPK phosphorylation.