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Toxic Effects of Urethane Dimethacrylate on Macrophages Through Caspase Activation, Mitochondrial Dysfunction, and Reactive Oxygen Species Generation

Urethane dimethacrylate (UDMA) is a dimethacrylate-based resin monomer that can react with other related monomers and inorganic particles, causing hydrophobic polymerization through cross-linking upon light activation. UDMA polymers are commonly used for the reconstruction and reinforcement of teeth...

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Autores principales: Chang, Chih-Yang, Chiang, Chen-Yu, Chiang, Yun-Wei, Lee, Min-Wei, Lee, Chien-Ying, Chen, Hung-Yi, Lin, Hui-Wen, Kuan, Yu-Hsiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361960/
https://www.ncbi.nlm.nih.gov/pubmed/32580382
http://dx.doi.org/10.3390/polym12061398
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author Chang, Chih-Yang
Chiang, Chen-Yu
Chiang, Yun-Wei
Lee, Min-Wei
Lee, Chien-Ying
Chen, Hung-Yi
Lin, Hui-Wen
Kuan, Yu-Hsiang
author_facet Chang, Chih-Yang
Chiang, Chen-Yu
Chiang, Yun-Wei
Lee, Min-Wei
Lee, Chien-Ying
Chen, Hung-Yi
Lin, Hui-Wen
Kuan, Yu-Hsiang
author_sort Chang, Chih-Yang
collection PubMed
description Urethane dimethacrylate (UDMA) is a dimethacrylate-based resin monomer that can react with other related monomers and inorganic particles, causing hydrophobic polymerization through cross-linking upon light activation. UDMA polymers are commonly used for the reconstruction and reinforcement of teeth and bones. UDMA can become unbound and be released from light-cured polymer resins. Thus far, no evidence exists on the toxic effects of UDMA and its related working mechanisms for macrophages. Therefore, in the present study, we investigated the cytotoxicity, mode of cell death, DNA damage, caspase activities, mitochondrial dysfunction, and reactive oxygen species (ROS) generation in RAW264.7 macrophages treated with UDMA using the lactate dehydrogenase (LDH) assay kit, Annexin V-FITC and PI assays, micronucleus formation and comet assay, caspase fluorometric assay, JC-1 assay, and 2ʹ,7ʹ-dichlorofluorescin diacetate (DCFH-DA) assay, respectively. Our results show that UDMA induced cytotoxicity; apoptosis and necrosis; genotoxicity, which is also called DNA damage; increased caspase-3, -8, and -9 activities; mitochondrial dysfunction; and intracellular ROS generation in a concentration-dependent manner in RAW264.7 macrophages. Thus, based on the observed inhibited concentration parallel trends, we concluded that UDMA induces toxic effects in macrophages. Furthermore, UDMA-induced intracellular ROS generation, cytotoxicity, and DNA damage were reduced by N-acetyl-L-cysteine.
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spelling pubmed-73619602020-07-21 Toxic Effects of Urethane Dimethacrylate on Macrophages Through Caspase Activation, Mitochondrial Dysfunction, and Reactive Oxygen Species Generation Chang, Chih-Yang Chiang, Chen-Yu Chiang, Yun-Wei Lee, Min-Wei Lee, Chien-Ying Chen, Hung-Yi Lin, Hui-Wen Kuan, Yu-Hsiang Polymers (Basel) Article Urethane dimethacrylate (UDMA) is a dimethacrylate-based resin monomer that can react with other related monomers and inorganic particles, causing hydrophobic polymerization through cross-linking upon light activation. UDMA polymers are commonly used for the reconstruction and reinforcement of teeth and bones. UDMA can become unbound and be released from light-cured polymer resins. Thus far, no evidence exists on the toxic effects of UDMA and its related working mechanisms for macrophages. Therefore, in the present study, we investigated the cytotoxicity, mode of cell death, DNA damage, caspase activities, mitochondrial dysfunction, and reactive oxygen species (ROS) generation in RAW264.7 macrophages treated with UDMA using the lactate dehydrogenase (LDH) assay kit, Annexin V-FITC and PI assays, micronucleus formation and comet assay, caspase fluorometric assay, JC-1 assay, and 2ʹ,7ʹ-dichlorofluorescin diacetate (DCFH-DA) assay, respectively. Our results show that UDMA induced cytotoxicity; apoptosis and necrosis; genotoxicity, which is also called DNA damage; increased caspase-3, -8, and -9 activities; mitochondrial dysfunction; and intracellular ROS generation in a concentration-dependent manner in RAW264.7 macrophages. Thus, based on the observed inhibited concentration parallel trends, we concluded that UDMA induces toxic effects in macrophages. Furthermore, UDMA-induced intracellular ROS generation, cytotoxicity, and DNA damage were reduced by N-acetyl-L-cysteine. MDPI 2020-06-22 /pmc/articles/PMC7361960/ /pubmed/32580382 http://dx.doi.org/10.3390/polym12061398 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chang, Chih-Yang
Chiang, Chen-Yu
Chiang, Yun-Wei
Lee, Min-Wei
Lee, Chien-Ying
Chen, Hung-Yi
Lin, Hui-Wen
Kuan, Yu-Hsiang
Toxic Effects of Urethane Dimethacrylate on Macrophages Through Caspase Activation, Mitochondrial Dysfunction, and Reactive Oxygen Species Generation
title Toxic Effects of Urethane Dimethacrylate on Macrophages Through Caspase Activation, Mitochondrial Dysfunction, and Reactive Oxygen Species Generation
title_full Toxic Effects of Urethane Dimethacrylate on Macrophages Through Caspase Activation, Mitochondrial Dysfunction, and Reactive Oxygen Species Generation
title_fullStr Toxic Effects of Urethane Dimethacrylate on Macrophages Through Caspase Activation, Mitochondrial Dysfunction, and Reactive Oxygen Species Generation
title_full_unstemmed Toxic Effects of Urethane Dimethacrylate on Macrophages Through Caspase Activation, Mitochondrial Dysfunction, and Reactive Oxygen Species Generation
title_short Toxic Effects of Urethane Dimethacrylate on Macrophages Through Caspase Activation, Mitochondrial Dysfunction, and Reactive Oxygen Species Generation
title_sort toxic effects of urethane dimethacrylate on macrophages through caspase activation, mitochondrial dysfunction, and reactive oxygen species generation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361960/
https://www.ncbi.nlm.nih.gov/pubmed/32580382
http://dx.doi.org/10.3390/polym12061398
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