JNK-mediated blockage of autophagic flux exacerbates the triethylene glycol dimethacrylate-induced mitochondrial oxidative damage and apoptosis in preodontoblast

Wang, Konghuai; Yu, Qihao; Wu, Danni; Liu, Ruona; Ren, Xuekun; Fu, Hui; Zhang, Xiaorong; Pan, Yihuai; Huang, Shengbin

doi:10.1016/j.cbi.2021.109432

Cited by 4 publications

(6 citation statements)

References 47 publications

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“…Previous studies have highlighted that TEGDMA induces apoptosis and necrosis in macrophages, preodontoblasts, and pulp cells [ 19 , 30 , 32 ]. During caecal ligation and puncture surgery, rutin inhibits cardiac apoptosis in high-glucose and sepsis-induced cardiomyopathy [ 33 , 34 ]. Rutin also decreases the rate of apoptosis in the liver and kidneys in rats with deltamethrin-induced hepatotoxicity and nephrotoxicity [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Rutin on Triethylene Glycol Dimethacrylate-Induced Toxicity through the Inhibition of Caspase Activation and Reactive Oxygen Species Generation in Macrophages

Yang

Chang

Yeh

et al. 2022

IJMS

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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.

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Section: Discussionmentioning

confidence: 99%

Protective Effect of Rutin on Triethylene Glycol Dimethacrylate-Induced Toxicity through the Inhibition of Caspase Activation and Reactive Oxygen Species Generation in Macrophages

Yang

Chang

Yeh

et al. 2022

IJMS

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“…These data indicated that melatonin attenuated TEGDMA-induced mDPC6T cell apoptosis. It is clear that TEGDMA-induced mDPC6T mitochondrial reactive oxygen species elevation and membrane potential decrease were significant [ 18 , 36 ]. Interestingly, melatonin significantly ameliorated mitochondrial ROS levels, as indicated by reduced MitoSOX staining intensity ( Figure 2 C,D).…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, we propose that melatonin plays a role in mitigating mitochondrial dysfunction-regulated apoptosis partly through the JNK/MAPK pathway. It has been reported that TEGDMA causes mitochondrial oxidative damage via JNK-dependent autophagy to exacerbate mDPC6T cell apoptosis [ 9 , 36 ]. Melatonin can modulate autophagy by various pathways.…”

Section: Discussionmentioning

confidence: 99%

“…The test compounds were prepared as stock solutions and diluted to the desired final concentrations immediately before use. Apoptosis was induced in mDPC6T cells by treatment with TEGDMA (2 mM) for 6 h [ 18 , 36 ]. To examine the protective effect of melatonin on TEGDMA-induced mDPC6T damage, varying concentrations of melatonin (50, 100, 150, and 200 μM) were added along with TEGDMA to the culture medium.…”

Section: Methodsmentioning

confidence: 99%

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Melatonin protects TEGDMA-induced preodontoblast mitochondrial apoptosis via the JNK/MAPK signaling pathway

Yu,

Hua,

Zhao

et al. 2024

ABBS

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Resin monomer-induced dental pulp injury presents a pathology related to mitochondrial dysfunction. Melatonin has been regarded as a strong mitochondrial protective bioactive compound from the pineal gland. However, it remains unknown whether melatonin can prevent dental pulp from resin monomer-induced injury. The aim of this study is to investigate the effects of melatonin on apoptosis of mouse preodontoblast cells (mDPC6T) induced by triethylene glycol dimethacrylate (TEGDMA), a major component in dental resin, and to determine whether the JNK/MAPK signaling pathway mediates the protective effect of melatonin. A well-established TEGDMA-induced mDPC6T apoptosis model is adopted to investigate the preventive function of melatonin by detecting cell viability, apoptosis rate, expressions of apoptosis-related proteins, mitochondrial ROS (mtROS) production, mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) level. Inhibitors of MAPKs are used to explore which pathway is involved in TEGDMA-induced apoptosis. Finally, the role of the JNK/MAPK pathway is verified using JNK agonists and antagonists. Our results show that melatonin attenuates TEGDMA-induced mDPC6T apoptosis by reducing mtROS production and rescuing MMP and ATP levels. Furthermore, mitochondrial dysfunction and apoptosis are alleviated only by the JNK/MAPK inhibitor SP600125 but not by other MAPK inhibitors. Additionally, melatonin downregulates the expression of phosphorylated JNK and counteractes the activating effects of anisomycin on the JNK/MAPK pathway, mimicking the effects of SP600125. Our findings demonstrate that melatonin protects mDPC6T cells against TEGDMA-induced apoptosis partly through JNK/MAPK and the maintenance of mitochondrial function, offering a novel therapeutic strategy for the prevention of resin monomer-induced dental pulp injury.

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“…Meanwhile, UDMA changes the normal morphology of dental pulp cells, lengthening or shortening normal spindle cells and reducing their activity [ 95 ]. Moreover, oxidative stress of gingival fibroblasts and pre-odontoblasts is initiated by TEGDMA through mitochondrial dysfunction [ 96 , 97 ]. The above are examples of the toxic effects of monomers on cells.…”

Section: Monomers Released During Biodegradation and Their Biological...mentioning

confidence: 99%

Biodegradation of Dental Resin-Based Composite—A Potential Factor Affecting the Bonding Effect: A Narrative Review

Guo

Gao

et al. 2022

Biomedicines

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In recent years, although resin composite has played an important role in the restoration of tooth defects, it still has several disadvantages, including being biodegraded by saliva, bacteria and other enzymes in the oral cavity, which may result in repair failure. This factor is not conducive to the long-term survival of the prosthesis in the mouth. In this article, we review the causes, influencing factors and prevention methods of resin biodegradation. Biodegradation is mainly caused by esterase in saliva and bacteria, which breaks the ester bond in resin and causes the release of monomers. The mechanical properties of the prosthesis can then be affected. Meanwhile, cathepsin and MMPs are activated on the bonding surface, which may decompose the dentin collagen. In addition, neutrophils and residual water on the bonding surface can also aggravate biodegradation. Currently, the primary methods to prevent biodegradation involve adding antibacterial agents to resin, inhibiting the activity of MMPs and enhancing the crosslinking of collagen fibers. All of the above indicates that in the preparation and adhesion of resin materials, attention should be paid to the influence of biodegradation to improve the prosthesis’s service life in the complex environment of the oral cavity.

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JNK-mediated blockage of autophagic flux exacerbates the triethylene glycol dimethacrylate-induced mitochondrial oxidative damage and apoptosis in preodontoblast

Cited by 4 publications

References 47 publications

Protective Effect of Rutin on Triethylene Glycol Dimethacrylate-Induced Toxicity through the Inhibition of Caspase Activation and Reactive Oxygen Species Generation in Macrophages

Protective Effect of Rutin on Triethylene Glycol Dimethacrylate-Induced Toxicity through the Inhibition of Caspase Activation and Reactive Oxygen Species Generation in Macrophages

Melatonin protects TEGDMA-induced preodontoblast mitochondrial apoptosis via the JNK/MAPK signaling pathway

Biodegradation of Dental Resin-Based Composite—A Potential Factor Affecting the Bonding Effect: A Narrative Review

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