Cytotoxicity and Pro-inflammatory Properties of Aliphatic Alpha, Beta-unsaturated Acid and Ester Monomers in RAW264.7 Cells and Their Chemical Reactivity

Abstract

Background/Aim: α,β-Unsaturated ester monomers such as methyl methacrylates (MMA), 2-hydroxyethyl methacrylates (2-HEMA), ethyleneglycol dimethacrylate (EGDMA) and triethyleneglycol dimetacrylate (TEGDMA) have been widely used in dentistry as dental materials. The present study was designed to clarify the proinflammatory activity of monomers. Materials and Methods: The cytotoxicity of the monomers and their effects on the expression of cyclooxygenase-2 (Cox2), nitric oxide synthase 2 (Nos2) and heme oxygenase 1 (Ho-1) mRNAs in RAW264.7 cells were determined using a cell counting kit and real-time reverse transcriptase-polymerase chain reaction, respectively. Results: The cytotoxicity declined in the order n-butyl acrylate (nBA) > acrylic acid > TEGDMA > EGDMA > methacrylic acid ≈ 2-HEMA > lauryl methacrylate > nBMA > MMA. nBA and EGDMA at 1 mM up-regulated the expression of Cox2 mRNA. In contrast, 1 mM nBA and 10 mM 2-HEMA up-regulated the expression of Nos2 mRNA. Up-regulation of Ho-1 mRNA expression was found for 0.1 mM nBA, 1 mM EGDMA and 2 mM TEGDMA. The electrophilicity, ω was calculated on the basis of the density function theory BLYP/6-31G*. Conclusion: nBA and EGDMA with high ω values exerted potent proinflammatory activities. nBA, EGDMA and TEGDMA upregulated Ho-1 gene expression. Ho-1 gene activation of monomers may promote resistance of chemical carcinogenesis in biological systems.

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

“…However, excess ROS production can cause peripheral tissue and cellular damage, DNA damage, lipid peroxidation, and pro-inflammatory response [ 14 , 15 , 16 ]. Recent several studies have shown that cytotoxicity was induced by TEGDMA in RAW264.7 macrophages via their large interaction potency and impregnation into lipid bilayers [ 17 ]. The incubation of macrophages with TEGDMA leads to various proinflammatory responses, such as the upregulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) [ 17 , 18 ].…”

Diels–Alder Cross-Linked, Washing-Free Hydrogel Films with Ordered Wrinkling Patterns for Multicellular Spheroid Generation

“…41 For monomer HEMA and crosslinker EGDMA, although they are widely used in biomedical areas it was reported that HEMA could induce apoptosis and cell-cycle delay 38,39 and EGDMA could exert proinflammatory activities. 40 To remove these compounds, the UV-cured PHEMA films were washed rigorously with PBS. As shown in Figure 10, the cells seeded on the washed films presented high viability, suggesting significantly improved biocompatibility of the films.…”

“…The biocompatibility and cytotoxicity of photoinitiators are always a big concern for their biomedical applications . For monomer HEMA and cross-linker EGDMA, although they are widely used in biomedical areas it was reported that HEMA could induce apoptosis and cell-cycle delay , and EGDMA could exert proinflammatory activities . To remove these compounds, the UV-cured PHEMA films were washed rigorously with PBS.…”

“…The UV irradiation step was further omitted by using redox polymerization, instead of photopolymerization, in the synthesis of PHEMA films . Although the PHEMA films were successfully synthesized and patterned, it was inevitable that some low molecular weight initiator, cross-linker, and monomer, which are potentially cytotoxic, − would remain in the resulting films and lower the biocompatibility of the films. For this reason, the films must be extensively washed to remove these low molecular weight compounds before cell seeding. ,, …”

A Review of the Biotechnological Production of Methacrylic Acid

“…The main mechanisms identified were the radical reactivity of MA and derivatives with cellular nucleophiles such as glutathione. MA has also been shown to directly induce DNA damage and inhibit key metabolic enzymes (Plaga et al, 2000;Ansteinsson et al, 2013;Arya et al, 2013;Curson et al, 2014;Murakami et al, 2019). This toxicity makes its direct biological production highly limited in any of the potential microbial hosts considered.…”