{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:26:22Z","timestamp":1791829582008,"version":"4.3.4"},"reference-count":57,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T00:00:00Z","timestamp":1664841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology of Taiwan","award":["MOST 109-2320-B-040-MY3"],"award-info":[{"award-number":["MOST 109-2320-B-040-MY3"]}]},{"name":"Ministry of Science and Technology of Taiwan","award":["MOST 110-2314-B-040-019"],"award-info":[{"award-number":["MOST 110-2314-B-040-019"]}]},{"name":"Ministry of Science and Technology of Taiwan","award":["CSH-2021-C-051"],"award-info":[{"award-number":["CSH-2021-C-051"]}]},{"name":"Ministry of Science and Technology of Taiwan","award":["CSH-2022-C-039"],"award-info":[{"award-number":["CSH-2022-C-039"]}]},{"name":"Chung Shan Medical University Hospital research program of Taiwan","award":["MOST 109-2320-B-040-MY3"],"award-info":[{"award-number":["MOST 109-2320-B-040-MY3"]}]},{"name":"Chung Shan Medical University Hospital research program of Taiwan","award":["MOST 110-2314-B-040-019"],"award-info":[{"award-number":["MOST 110-2314-B-040-019"]}]},{"name":"Chung Shan Medical University Hospital research program of Taiwan","award":["CSH-2021-C-051"],"award-info":[{"award-number":["CSH-2021-C-051"]}]},{"name":"Chung Shan Medical University Hospital research program of Taiwan","award":["CSH-2022-C-039"],"award-info":[{"award-number":["CSH-2022-C-039"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rutin, also called quercetin-3-rhamnosyl glucoside, is a natural flavonol glycoside present in many plants. Rutin is used to treat various diseases, such as inflammation, diabetes, and cancer. For polymeric biomaterials, triethylene glycol dimethacrylate (TEGDMA) is the most commonly used monomer and serves as a restorative resin, a dentin bonding agent and sealant, and a bone cement component. Overall, TEGDMA induces various toxic effects in macrophages, including cytotoxicity, apoptosis, and genotoxicity. The aim of this study was to investigate the protective mechanism of rutin in alleviating TEGDMA-induced toxicity in RAW264.7 macrophages. After treatment with rutin, we assessed the cell viability and apoptosis of TEGDMA-induced RAW264.7 macrophages using an methylthiazol tetrazolium (MTT) assay and Annexin V-FITC\/propidium iodide assay, respectively. Subsequently, we assessed the level of genotoxicity using comet and micronucleus assays, assessed the cysteinyla aspartate specific proteinases (caspases) and antioxidant enzyme (AOE) activity using commercial kits, and evaluated the generation of reactive oxygen species (ROS) using a dichlorodihydrofluorescein diacetate (DCFH-DA) assay. We evaluated the expression of heme oxygenase (HO)-1, the expression of nuclear factor erythroid 2 related factor (Nrf-2), and phosphorylation of AMP activated protein kinase (AMPK) using the Western blot assay. The results indicated that rutin substantially reduced the level of cytotoxicity, apoptosis, and genotoxicity of TEGDMA-induced RAW264.7 macrophages. Rutin also blocked the activity of caspase-3, caspase-8, and caspase-9 in TEGDMA-stimulated RAW264.7 macrophages. In addition, it decreased TEGDMA-induced ROS generation and AOE deactivation in macrophages. Finally, we found that TEGDMA-inhibited slightly the HO-1 expression, Nrf-2 expression, and AMPK phosphorylation would be revered by rutin. In addition, the HO-1 expression, Nrf-2 expression, and AMPK phosphorylation was enhanced by rutin. These findings indicate that rutin suppresses TEGDMA-induced caspase-mediated toxic effects through ROS generation and antioxidative system deactivation through the Nrf-2\/AMPK pathway. Therefore, rutin has the potential to serve as a novel antitoxicity agent for TEGDMA in RAW264.7 macrophages.<\/jats:p>","DOI":"10.3390\/ijms231911773","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T23:39:31Z","timestamp":1665272371000},"page":"11773","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Protective Effect of Rutin on Triethylene Glycol Dimethacrylate-Induced Toxicity through the Inhibition of Caspase Activation and Reactive Oxygen Species Generation in Macrophages"],"prefix":"10.3390","volume":"23","author":[{"given":"Li-Chiu","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Dentistry, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"},{"name":"School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9731-2577","authenticated-orcid":false,"given":"Yu-Chao","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"},{"name":"School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun-Lin","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, National Chung Hsing University, Taichung 40227, Taiwan"},{"name":"Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Pharmacy, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu-Mei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"},{"name":"School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni-Yu","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"},{"name":"School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8991-6394","authenticated-orcid":false,"given":"Yu-Hsiang","family":"Kuan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Pharmacy, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jsps.2016.04.025","article-title":"The pharmacological potential of rutin","volume":"25","author":"Ganeshpurkar","year":"2017","journal-title":"J. Saudi Pharm. Soc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6241017","DOI":"10.1155\/2018\/6241017","article-title":"Rutin as a Potent Antioxidant: Implications for Neurodegen-erative Disorders","volume":"2018","author":"Enogieru","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6063","DOI":"10.1007\/s11033-022-07395-0","article-title":"Rutin protects rat liver and kidney from sodium valproate-induce damage by attenuating oxidative stress, ER stress, inflammation, apoptosis and autophagy","volume":"49","author":"Kandemir","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Tung, Y.T., Zeng, J.L., Ho, S.T., Xu, J.W., Lin, I.H., and Wu, J.H. (2021). Djulis Hull Improves Insulin Resistance and Modulates the Gut Microbiota in High-Fat Diet (HFD)-Induced Hyperglycaemia. Antioxidants, 11.","DOI":"10.3390\/antiox11010045"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"379","DOI":"10.2174\/1567201818666211005090656","article-title":"Formulation and Characterization of Rutin Loaded Chitosan-alginate Nanoparticles: Antidiabetic and Cytotoxicity Studies","volume":"19","author":"Surendra","year":"2022","journal-title":"Curr. Drug Deliv."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"153909","DOI":"10.1016\/j.phymed.2021.153909","article-title":"Quercetin- and rutin-based nano-formulations for cancer treatment: A systematic review of improved efficacy and molecular mechanisms","volume":"97","author":"Mondal","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1515\/jcim-2015-0078","article-title":"Attenuation of genotoxicity, oxidative stress, apoptosis and inflammation by rutin in benzo(a)pyrene exposed lungs of mice: Plausible role of NF-\u03baB, TNF-\u03b1 and Bcl-2","volume":"13","author":"Shahid","year":"2016","journal-title":"J. Complement. Integr. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/tox.23009","article-title":"Rutin-protected BisGMA-induced cytotoxicity, genotoxicity, and apoptosis in macrophages through the reduction of the mitochondrial apoptotic pathway and induction of antioxidant enzymes","volume":"36","author":"Huang","year":"2020","journal-title":"Environ. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"115129","DOI":"10.1016\/j.jep.2022.115129","article-title":"Leonurus japonicus Houttuyn induces reactive oxygen species-mediated apoptosis via regulation of miR-19a-3p\/PTEN\/PI3K\/AKT in U937 and THP-1 cells","volume":"291","author":"Park","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s00056-021-00292-4","article-title":"Elution study of acrylic monomers from orthodontic materials using high performance liquid chromatography (HPLC)","volume":"83","author":"Kux","year":"2022","journal-title":"J. Orofac. Orthop."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1002\/cre2.296","article-title":"The effects of the dental methacrylates TEGDMA, Bis-GMA, and UDMA on neutrophils in vitro","volume":"6","author":"Alizadehgharib","year":"2020","journal-title":"Clin. Exp. Dent. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/0300-5712(95)00036-4","article-title":"Diffusion of monomers from bonding resin-resin composite combinations through dentine in vitro","volume":"24","author":"Gerzina","year":"1996","journal-title":"J. Dent."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/s41574-022-00675-6","article-title":"Macrophage functional diversity in NAFLD-more than inflammation","volume":"18","author":"Barreby","year":"2022","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Herb, M., and Schramm, M. (2021). Functions of ROS in Macrophages and Antimicrobial Immunity. Antioxidants, 10.","DOI":"10.3390\/antiox10020313"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"734229","DOI":"10.3389\/fimmu.2021.734229","article-title":"Reactive Oxygen Species in Macrophages: Sources and Targets","volume":"12","author":"Canton","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"114152","DOI":"10.1016\/j.envres.2022.114152","article-title":"Oxidative stress and DNA damage resulting from welding fumes exposure among professional welders: A systematic review and meta-analysis","volume":"214","author":"Rafiee","year":"2022","journal-title":"Environ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"313","DOI":"10.21873\/invivo.11477","article-title":"Cytotoxicity and Pro-inflammatory Properties of Aliphatic Alpha, Beta-unsaturated Acid and Ester Monomers in RAW264.7 Cells and Their Chemical Reactivity","volume":"33","author":"Murakami","year":"2019","journal-title":"In Vivo"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.dental.2008.05.014","article-title":"Effects of TEGDMA and HEMA on the expression of COX-2 and iNOS in cultured murine macrophage cells","volume":"25","author":"Lee","year":"2009","journal-title":"Dent. Mater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1002\/tox.21935","article-title":"Cytotoxicity and genotoxicity of triethyleneglycol-dimethacrylate in macrophages involved in DNA damage and caspases activation","volume":"30","author":"Huang","year":"2015","journal-title":"Environ. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.biomaterials.2011.10.026","article-title":"Function of MAPK and downstream transcription factors in monomer-induced apoptosis","volume":"33","author":"Krifka","year":"2012","journal-title":"Biomaterials"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1016\/j.biomaterials.2010.11.031","article-title":"Activation of stress-regulated transcription factors by triethylene glycol dimethacrylate monomer","volume":"32","author":"Krifka","year":"2011","journal-title":"Biomaterials"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.redox.2017.04.014","article-title":"Time-dependent effect of rutin on skin fibroblasts membrane disruption following UV radiation","volume":"12","author":"Bielawska","year":"2017","journal-title":"Redox. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4721352","DOI":"10.1155\/2017\/4721352","article-title":"Rutin as a Mediator of Lipid Metabolism and Cellular Signaling Pathways Interactions in Fibroblasts Altered by UVA and UVB Radiation","volume":"2017","author":"Skrzydlewska","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9314342","DOI":"10.1155\/2021\/9314342","article-title":"1-Nitropyrene Induced Reactive Oxygen Species-Mediated Apoptosis in Macrophages through AIF Nuclear Translocation and AMPK\/Nrf-2\/HO-1 Pathway Activation","volume":"2021","author":"Su","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"112962","DOI":"10.1016\/j.ecoenv.2021.112962","article-title":"3-Bromofluoranthene-induced cardiotoxicity of zebrafish and apoptosis in the vascular endothelial cells via intrinsic and extrinsic caspase-dependent pathways","volume":"228","author":"Su","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/tox.23384","article-title":"Bisphenol A induced apoptosis via oxidative stress generation involved Nrf2\/HO-1 pathway and mitochondrial dependent pathways in human retinal pigment epithelium (ARPE-19) cells","volume":"37","author":"Chiang","year":"2022","journal-title":"Environ. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"112062","DOI":"10.1016\/j.ecoenv.2021.112062","article-title":"Genotoxic effects of 1-nitropyrene in macrophages are mediated through a p53-dependent pathway involving cytochrome c release, caspase activation, and PARP-1 cleavage","volume":"213","author":"Wu","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sun, Y., Wang, X., Gong, Q., Li, J., Huang, H., Xue, F., Dai, J., and Tang, F. (2022). Extraintestinal Pathogenic Escherichia coli Utilizes Surface-Located Elongation Factor G to Acquire Iron from Holo-Transferrin. Microbiol. Spectr., 10.","DOI":"10.1128\/spectrum.01662-21"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"620510","DOI":"10.3389\/fimmu.2021.620510","article-title":"Function of Macrophages in Disease: Current Understanding on Molecular Mechanisms","volume":"12","author":"Zhang","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.3389\/fphar.2019.01255","article-title":"Targeting Macrophages: Friends or Foes in Disease?","volume":"10","author":"Ardura","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00784-004-0293-0","article-title":"Cytotoxicity evaluation of dental resin composites and their flowable derivatives","volume":"9","author":"Darmani","year":"2005","journal-title":"Clin. Oral Investig."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Lov\u00e1sz, B.V., Berta, G., Lempel, E., S\u00e9t\u00e1l\u00f3, G., Vecserny\u00e9s, M., and Szalma, J. (2021). TEGDMA (Triethylene Glycol Dimethacrylate) Induces Both Caspase-Dependent and Caspase-Independent Apoptotic Pathways in Pulp Cells. Polymers, 13.","DOI":"10.3390\/polym13050699"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"109336","DOI":"10.1016\/j.cbi.2020.109336","article-title":"Dental resin monomers induce early and potent oxidative damage on human odontoblast-like cells","volume":"333","author":"Baldion","year":"2021","journal-title":"Chem. Biol. Interact."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"109432","DOI":"10.1016\/j.cbi.2021.109432","article-title":"JNK-mediated blockage of autophagic flux exacerbates the triethylene glycol dimethacrylate-induced mitochondrial oxidative damage and apoptosis in preodontoblast","volume":"339","author":"Wang","year":"2021","journal-title":"Chem. Biol. Interact."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"944","DOI":"10.3892\/etm.2021.10376","article-title":"Rutin alleviates cardiomyocyte injury induced by high glucose through inhibiting apoptosis and endoplasmic reticulum stress","volume":"22","author":"Wang","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"834077","DOI":"10.3389\/fphys.2022.834077","article-title":"Rutin Inhibits Cardiac Apoptosis and Prevents Sepsis-Induced Cardiomyopathy","volume":"13","author":"Meng","year":"2022","journal-title":"Front. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"62975","DOI":"10.1007\/s11356-021-15190-w","article-title":"Protective effects of rutin against deltamethrin-induced hepatotoxicity and nephrotoxicity in rats via regulation of oxidative stress, inflammation, and apoptosis","volume":"28","author":"Kandemir","year":"2021","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/tox.23432","article-title":"DNA damage and cell apoptosis induced by fungicide difenoconazole in mouse mononuclear macrophage RAW264.7","volume":"37","author":"Li","year":"2022","journal-title":"Environ. Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Schaffert, A., Arnold, J., Karkossa, I., Bl\u00fcher, M., von Bergen, M., and Schubert, K. (2021). The Emerging Plasticizer Alternative DINCH and Its Metabolite MINCH Induce Oxidative Stress and Enhance Inflammatory Responses in Human THP-1 Macrophages. Cells, 10.","DOI":"10.3390\/cells10092367"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"638","DOI":"10.4012\/dmj.2016-316","article-title":"NAC ameliorates dental composite-induced DNA double-strand breaks and chromatin condensation","volume":"36","author":"Styllou","year":"2017","journal-title":"Dent. Mater. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.dental.2015.04.009","article-title":"Assessment of HEMA and TEGDMA induced DNA damage by multiple genotoxicological endpoints in human lymphocytes","volume":"31","author":"Ginzkey","year":"2015","journal-title":"Dent. Mater."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/jbm.b.31960","article-title":"Glutathione level and genotoxicity in human oral keratinocytes exposed to TEGDMA","volume":"100","author":"Volk","year":"2012","journal-title":"J. Biomed. Mater Res. B Appl. Biomater."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1080\/01480545.2018.1465948","article-title":"Modulatory role of rutin on 2,5-hexanedione-induced chromosomal and DNA damage in rats: Validation of computational predictions","volume":"43","author":"Muhammad","year":"2020","journal-title":"Drug Chem. Toxicol."},{"key":"ref_44","first-page":"390","article-title":"Effect of rutin on oxidative DNA damage in PC12 neurons cultured in nutrients deprivation condition","volume":"23","author":"Ghorbani","year":"2020","journal-title":"Iran J. Basic Med. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/cdd.2014.216","article-title":"Old, new and emerging functions of caspases","volume":"22","author":"Shalini","year":"2015","journal-title":"Cell. Death Differ."},{"key":"ref_46","first-page":"1","article-title":"Ameliorating effect of rutin against diclofenac-induced cardiac injury in rats with underlying function of FABP3, MYL3, and ANP","volume":"4","author":"Dogra","year":"2022","journal-title":"Drug Chem. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.neuro.2022.03.005","article-title":"The protective effect of rutin against the cisplatin-induced cochlear damage in vitro","volume":"90","author":"Zheng","year":"2022","journal-title":"Neurotoxicology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1038\/sj.jid.5701141","article-title":"NF-kappaB inhibition reveals differential mechanisms of TNF versus TRAIL-induced apoptosis upstream or at the level of caspase-8 activation independent of cIAP2","volume":"128","author":"Diessenbacher","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_49","first-page":"595","article-title":"Caspase-dependent and -independent cell death pathways after DNA damage (Review)","volume":"14","author":"Kim","year":"2005","journal-title":"Oncol. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4326","DOI":"10.1073\/pnas.1819473116","article-title":"Reactive oxygen species modulate macrophage immunosuppressive phenotype through the up-regulation of PD-L1","volume":"116","author":"Roux","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1002\/jbm.a.36600","article-title":"TEGDMA releasing in resin composites with different filler contents and its correlation with mitochondrial mediated cytotoxicity in human gingival fibroblasts","volume":"107","author":"Liu","year":"2019","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1007\/s00784-014-1370-7","article-title":"NADPH oxidase 4 is involved in the triethylene glycol dimethacrylate-induced reactive oxygen species and apoptosis in human embryonic palatal mesenchymal and dental pulp cells","volume":"19","author":"Yeh","year":"2015","journal-title":"Clin. Oral Investig."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Zandi, P., and Schnug, E. (2022). Reactive Oxygen Species, Antioxidant Responses and Implications from a Microbial Modulation Perspective. Biology, 11.","DOI":"10.3390\/biology11020155"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.bcp.2018.02.010","article-title":"The macrophage heme-heme oxygenase-1 system and its role in inflammation","volume":"153","author":"Vijayan","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1007\/s00018-016-2223-0","article-title":"Role of Nrf2\/HO-1 system in development, oxidative stress response and diseases: An evolutionarily conserved mechanism","volume":"73","author":"Loboda","year":"2016","journal-title":"Cellular Mol. Life Sci.: CMLS"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"101393","DOI":"10.1016\/j.redox.2019.101393","article-title":"AMPK leads to phosphorylation of the transcription factor Nrf2, tuning transactivation of selected target genes","volume":"29","author":"Matzinger","year":"2020","journal-title":"Redox Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1007\/s12011-021-02764-5","article-title":"Rutin Ameliorates Cadmium-Induced Necroptosis in the Chicken Liver via Inhibiting Oxidative Stress and MAPK\/NF-\u03baB Pathway","volume":"200","author":"Liu","year":"2022","journal-title":"Biol. Trace Elem. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11773\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:46:25Z","timestamp":1760143585000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11773"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,4]]},"references-count":57,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911773"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911773","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,4]]}}}