N-acetyl cysteine directed detoxification of 2-hydroxyethyl methacrylate by adduct formation

Nocca, Giuseppina; D’Antò, Vincenzo; Desiderio, Claudia; Rossetti, Diana Valeria; Valletta, Rosa; Baquala, Adriana Marquez; Schweikl, Helmut; Lupi, Alessandro; Rengo, Sandro; Spagnuolo, Gianrico

doi:10.1016/j.biomaterials.2009.12.015

Cited by 45 publications

(45 citation statements)

References 45 publications

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“…Here, we demonstrated that co-treatment with 5 mM NAC induced an increase in cell proliferation, a reduction in cell apoptosis and a reverse in cell cycle perturbation, confirming the in vitro detoxification ability of NAC against Bis-GMA in HOK cells. It appeared that NAC counteracted the toxicity of monomers mainly through its ability in balancing the cellular redox status, although NAC might also follow other alternative mechanisms like formation of NAC-monomer adduct or induction of cell differentiation (Paranjpe et al, 2007, Nocca et al, 2010. Interestingly, previous investigations have demonstrated that 5 mM NAC provided better protects against monomers than 1 mM NAC, whereas the worst was 10 mM NAC (Eckhardt et al, 2009).…”

Section: Discussionmentioning

confidence: 89%

“…Previous investigations (Geurtsen et al, 1998) showed that the resistance against resin monomers depend on the cells used for testing. These differences between cell lines might be related to structural physical-chemical properties of each cell phenotype (Nocca et al, 2010). In addition, the intracellular concentration might be varied in different cell lines, though monomers available in the extracellular culture medium are the same (Nocca et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

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N-acetyl cysteine protects human oral keratinocytes from Bis-GMA-induced apoptosis and cell cycle arrest by inhibiting reactive oxygen species-mediated mitochondrial dysfunction and the PI3K/Akt pathway

Zhu

et al. 2015

Toxicology in Vitro

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

N-acetyl cysteine protects human oral keratinocytes from Bis-GMA-induced apoptosis and cell cycle arrest by inhibiting reactive oxygen species-mediated mitochondrial dysfunction and the PI3K/Akt pathway

Zhu

et al. 2015

Toxicology in Vitro

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“…Additionally, it has been revealed that HEMA increases the intracellular ROS level and depletes the intracellular GSH stores, leading to cell cycle perturbation and apoptosis [35–37]. The HEMA-induced cell cycle perturbation can be inhibited by the addition of N -acetyl- l -cysteine (NAC), in which the NAC undergoes Michael addition to methacryloyl group of HEMA and form NAC-HEMA adduct [38]. Herein, this cellular oxidative stress is also caused by Michael addition between a sulfhydryl group of GSH and the methacryloyl groups of the monomers [39].…”

Section: Discussionmentioning

confidence: 99%

Sensitization Potential of Dental Resins: 2-Hydroxyethyl Methacrylate and Its Water-Soluble Oligomers Have Immunostimulatory Effects

et al. 2013

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The immunostimulatory effects of the representative dental resin monomer 2-hydroxyethyl methacrylate (HEMA), a HEMA derivative that does not contain a double bond (2-hydroxyethyl isobutyrate, HEIB), and polymerized water-soluble oligomers of HEMA (PHEMA) were investigated. It is known that expression levels of either or both of CD54 and CD86 in THP-1 cells are increased by exposure to sensitizing substances. In this study, the expression levels of CD54 and CD86, the production of reactive oxygen species (ROS), and the viability of the cells were measured after 24 h of incubation with these materials at different concentrations. The concentrations of the materials that induced the expression of both CD54 and CD86 were low in the following order: NiSO4, HEMA, and methyl methacrylate (MMA). These results indicate that these dental resin monomers have lower sensitizing potentials than NiSO4. Although HEIB, which lacks a double bond, resulted in negligible ROS production and reduced cytotoxicity than HEMA, it induced the expression of CD54 and CD86. Comparison of the results for HEMA and HEIB indicates that dental resin monomer-induced sensitization may be related not only to the oxidative stress related to the methacryloyl group but also to the structures of these compounds. Of particular interest is the result that a water-soluble PHEMA oligomer with a relatively high-molecular weight also exhibited negligible cytotoxicity, whereas the expression level of CD54 increased after exposure to PHEMA at a high concentration. This result serves as a warning that polymerized substances also have the potential to induce sensitization. This study provides insight into the nature of allergic responses to dental resin materials in clinical use and may facilitate the development of more biocompatible restorative materials in the future.

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“…Methacrylate monomers can reach millimolar concentrations at least in the pulp and that is why they are used at relatively high concentrations of up to 2.5 × 10 −2 mol/l and above, in many in vitro studies [10, 14]. Recently, Nocca et al [49] showed that the concentrations of HEMA inside 3T3 fibroblasts was 15–20 times lower than that present in the cells’ medium, when added in the range 1–8 mM.…”

Section: Discussionmentioning

confidence: 99%

2-Hydroxylethyl methacrylate (HEMA), a tooth restoration component, exerts its genotoxic effects in human gingival fibroblasts trough methacrylic acid, an immediate product of its degradation

et al. 2011

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HEMA (2-hydroxyethyl methacrylate), a methacrylate commonly used in dentistry, was reported to induce genotoxic effects, but their mechanism is not fully understood. HEMA may be degraded by the oral cavity esterases or through mechanical stress following the chewing process. Methacrylic acid (MAA) is the primary product of HEMA degradation. In the present work we compared cytotoxic and genotoxic effects induced by HEMA and MAA in human gingival fibroblasts (HGFs). A 6-h exposure to HEMA or MAA induced a weak decrease in the viability of HGFs. Neither HEMA nor MAA induced strand breaks in the isolated plasmid DNA, but both compounds evoked DNA damage in HGFs, as evaluated by the alkaline comet assay. Oxidative modifications to the DNA bases were monitored by the DNA repair enzymes Endo III and Fpg. DNA damage induced by HEMA and MAA was not persistent and was removed during a 120 min repair incubation. Results from the neutral comet assay indicated that both compounds induced DNA double strand breaks (DSBs) and they were confirmed by the γ-H2AX assay. Both compounds induced apoptosis and perturbed the cell cycle. Therefore, methacrylic acid, a product of HEMA degradation, may be involved in its cytotoxic and genotoxic action.

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N-acetyl cysteine directed detoxification of 2-hydroxyethyl methacrylate by adduct formation

Cited by 45 publications

References 45 publications

N-acetyl cysteine protects human oral keratinocytes from Bis-GMA-induced apoptosis and cell cycle arrest by inhibiting reactive oxygen species-mediated mitochondrial dysfunction and the PI3K/Akt pathway

N-acetyl cysteine protects human oral keratinocytes from Bis-GMA-induced apoptosis and cell cycle arrest by inhibiting reactive oxygen species-mediated mitochondrial dysfunction and the PI3K/Akt pathway

Sensitization Potential of Dental Resins: 2-Hydroxyethyl Methacrylate and Its Water-Soluble Oligomers Have Immunostimulatory Effects

2-Hydroxylethyl methacrylate (HEMA), a tooth restoration component, exerts its genotoxic effects in human gingival fibroblasts trough methacrylic acid, an immediate product of its degradation

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