# Oxidative Stress, Pro-Inflammatory Response, Cytotoxicity and Apoptosis Induced by Contemporary Endodontic Sealers in Human Periodontal Ligament Fibroblasts

**Authors:** Stanisław Krokosz, Virginia Ewa Lis, Sara Zięba, Mateusz Maciejczyk, Ewa Zalewska, Maria Obrycka, Edyta Gołaś, Małgorzata Żendzian-Piotrowska, Jerzy Ładny, Anna Skutnik-Radziszewska, Karol Dąbrowski, Julia Kuźmiuk, Anna Zalewska

PMC · DOI: 10.3390/jfb17020105 · 2026-02-22

## TL;DR

This study compares how different dental sealers affect human periodontal cells, finding some cause more inflammation and protein damage than others.

## Contribution

The study provides a comparative analysis of oxidative stress, inflammation, and cytotoxicity of eight modern endodontic sealers in human periodontal ligament fibroblasts.

## Key findings

- Calcium silicate-based sealers showed better redox profiles and less protein oxidation compared to calcium hydroxide-based sealers.
- EndoSeal MTA and AH Plus increased pro-inflammatory cytokine release, while BioRoot TM showed the lowest cytokine expression.
- All sealers induced minimal apoptosis, with TotalFill BC maintaining high cell viability.

## Abstract

The biological compatibility of endodontic sealers is a key determinant of periapical tissue healing. This in vitro study investigated the cytotoxic, pro-inflammatory, and redox-related effects of eight endodontic sealers on human periodontal ligament fibroblasts (HPdLFs): Biopulp (Chema-Elektromet), AH Plus (Dentsply Sirona), MTA Fillapex (Angelus), EndoSeal MTA (Maruchi), GuttaFlow (Coltène), AH Plus Bioceramic (Dentsply Sirona), TotalFill BC (FKG Dentaire SA), and BioRoot TM (Septodont). Cells were exposed for 24 h to 10-fold-diluted sealer extracts prepared in accordance with the manufacturers’ instructions, while control samples underwent identical procedures without sealer contact. Oxidative stress biomarkers, antioxidant defense parameters, protein oxidation indices, apoptotic activity (caspase-3), pro-inflammatory cytokines (IL-1, IL-6), and cell viability (MTT assay) were assessed. Under the applied conditions, all materials induced only limited global oxidative stress, with most alterations reflecting selective protein and glycoxidative modifications. Nevertheless, AH Plus, MTA Fillapex, and the calcium hydroxide-based Biopulp exhibited a less favorable redox profile and greater protein oxidation compared with calcium silicate-based sealers. AH Plus and EndoSeal MTA were associated with increased IL-6 release, whereas EndoSeal MTA moderately elevated IL-1 levels. BioRoot TM demonstrated the lowest cytokine expression, and TotalFill BC preserved high cell viability. Caspase-3 activity remained comparable across all experimental groups, indicating minimal induction of apoptosis.

## Linked entities

- **Proteins:** Casp3 (caspase 3)
- **Chemicals:** IL-1 (PubChem CID 139555045), IL-6 (PubChem CID 165368475)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, PLK3 (polo like kinase 3) [NCBI Gene 1263] {aka CNK, FNK, PLK-3, PRK}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, INS (insulin) [NCBI Gene 483665], ABL2 (ABL proto-oncogene 2, non-receptor tyrosine kinase) [NCBI Gene 27] {aka ABLL, ARG}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CAT (catalase) [NCBI Gene 847], RENBP (renin binding protein) [NCBI Gene 5973] {aka RBP, RNBP}, GSS (glutathione synthetase) [NCBI Gene 2937] {aka CNSHA6, GSHS, HEL-S-64p, HEL-S-88n}
- **Diseases:** mitochondrial dysfunction (MESH:D028361), Inflammatory (MESH:D007249), injury to (MESH:D014947), diabetes (MESH:D003920), bone fragility (MESH:C536063), Cytotoxicity (MESH:D064420), AOPPs (MESH:D020178), infected (MESH:D007239), bacterial (MESH:D001424), chronic (MESH:D002908)
- **Chemicals:** thionitrobenzoic acid (MESH:C011136), 1-methyl-2-phenylindole (MESH:C520322), formazan (MESH:D005562), AH Plus (MESH:C534916), sodium chloride (MESH:D012965), MTA Fillapex (MESH:C086631), adrenaline (MESH:D004837), Calcium silicate (MESH:C031293), DT (MESH:C007543), EDTA (MESH:D004492), GuttaFlow (MESH:C515718), advanced glycation end products (MESH:D017127), tyrosine (MESH:D014443), Argpyrimidine (MESH:C107313), iodide (MESH:D007454), Biopulp (MESH:C028835), glycine (MESH:D005998), silicone (MESH:D012828), 4-HNE (MESH:C027576), xylenol orange (MESH:C016833), KN (MESH:D007737), 5,5'-dithiobis-(2-nitrobenzoic acid) (MESH:D004228), bismuth (MESH:D001729), HEPES (MESH:D006531), MTA (MESH:D000068437), superoxide (MESH:D013481), Ac-Asp-Glu-Val-Asp-pNA (-), H2O2 (MESH:D006861), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MESH:C022616), Chema (MESH:C057647), zirconium (MESH:D015040), hydroxyapatite (MESH:D017886), amines (MESH:D000588), N-formylkynurenine (MESH:C007772), arginine (MESH:D001120), TM (MESH:D013932), Epoxy resin (MESH:D004853), peroxides (MESH:D010545), thiol (MESH:D013438), calcium hydroxide (MESH:D002126), MTT (MESH:C070243), NADPH (MESH:D009249), adrenochrome (MESH:D000323), lipid (MESH:D008055), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (MESH:C002502), methanesulfonic acid (MESH:C045880), Resin (MESH:D012116), iodine (MESH:D007455), PEN (MESH:C062187), methylglyoxal (MESH:D011765), bicinchoninic acid (MESH:C047117), Biodentine (MESH:C506393), GSH (MESH:D005978), CO2 (MESH:D002245), DMSO (MESH:D004121), calcium (MESH:D002118), H2SO4 (MESH:C033158), lysine (MESH:D008239), tryptophan (MESH:D014364)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** HDPSC — Homo sapiens (Human), Somatic stem cell (CVCL_AV90)

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12942283/full.md

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Source: https://tomesphere.com/paper/PMC12942283