title: BisGMA-induced cytotoxicity and genotoxicity in macrophages are attenuated by wogonin via reduction of intrinsic caspase pathway activation.
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.
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Fu-Mei
authors.initials: FM
authors.lastname: Huang
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Yu-Chao
authors.initials: YC
authors.lastname: Chang
authors.affiliation: School of Public Health, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shiuan-Shinn
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Department of Neurology, Show Chwan Memorial Hospital, Changhua, Taiwan.|Department of Nursing, College of Medicine & Nursing, Hung Kuang University, Taichung, Taiwan.
authors.forename: Chung-Hsin
authors.initials: CH
authors.lastname: Yeh
authors.affiliation: School of Public Health, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Kevin Gee
authors.initials: KG
authors.lastname: Lee
authors.affiliation: School of Health, National Taichung University of Science and Technology, Taichung, Taiwan.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Chun-Jung
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan.
authors.forename: Pin-Ho
authors.initials: PH
authors.lastname: Pan
authors.affiliation: Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Kuan
mesh_terms: D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D017438:Bisphenol A-Glycidyl Methacrylate / Q000633:toxicity*; D020169:Caspases / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D053938:DNA Fragmentation; D044950:Flavanones / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D010718:Phosphatidylserines / Q000378:metabolism; D000067996:RAW 264.7 Cells; D012117:Resins, Synthetic / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016587:Antimutagenic Agents; D044950:Flavanones; D016166:Free Radical Scavengers; D009153:Mutagens; D010718:Phosphatidylserines; D012117:Resins, Synthetic; D017438:Bisphenol A-Glycidyl Methacrylate; D020169:Caspases; C085514:wogonin
keywords: BisGMA; caspase; cytotoxicity; genotoxicity; wogonin