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BisGMA‐induced cytotoxicity and genotoxicity in macrophages are attenuated by wogonin via reduction of intrinsic caspase pathway activation
Authors:Yu‐Chao Chang  Shiuan‐Shinn Lee  Kevin Gee Lee  Yi‐Chun Huang  Chun‐Jung Chen  Wen‐Ying Chen  Pin‐Ho Pan  Yu‐Hsiang Kuan
Affiliation:1. School of Dentistry, Chung Shan Medical University, Taichung, Taiwan;2. School of Public Health, Chung Shan Medical University, Taichung, Taiwan;3. School of Health, National Taichung University of Science and Technology, Taichung, Taiwan;4. Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan;5. Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan;6. Department of Pediatrics, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan;7. Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan;8. Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan
Abstract: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.
Keywords:BisGMA  wogonin  cytotoxicity  genotoxicity  caspase
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