BisGMA‐induced cytotoxicity and genotoxicity in macrophages are attenuated by wogonin via reduction of intrinsic caspase pathway activation

Bisphenol‐A‐glycidyldimethacrylate (BisGMA) is a frequently used monomer in dental restorative resins. However, BisGMA could leach from dental restorative resins after polymerization leading to inflammation in the peripheral environment. Wogonin, a natural flavone derivative, has several benefits, such as antioxidative, anti‐inflammatory and neuroprotective properties. Pretreatment of macrophage RAW264.7 cells with wogonin inhibited cytotoxicity which is induced by BisGMA in a concentration‐dependent manner. BisGMA induced apoptotic responses, such as redistribution of phosphatidylserine from the internal to the external membrane and DNA fragmentation, were decreased by wogonin in a concentration‐dependent manner. In addition, BisGMA‐induced genotoxicity, which detected by cytokinesis‐blocked micronucleus and single‐cell gel electrophoresis assays, were inhibited by wogonin in a concentration‐dependent manner. Furthermore, wogonin suppressed BisGMA–induced activation of intrinsic caspase pathways, such as caspases‐3 and −8. Parallel trends were observed in inhibition of caspase‐3 and −8 activities, apoptosis, and genotoxicity. These results indicate wogonin suppressed the BisGMA‐induced apoptosis and genotoxicity mainly via intrinsic caspase pathway in macrophages. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 176–184, 2016.