Salivary NETosis-Related and Oxidative Stress Biomarkers Define a Conventional Cigarette Smoking-Associated Inflammatory Phenotype in Periodontitis: A Cross-Sectional Observational Study

Sufaru, Irina-Georgeta; Lazar, Luminita; Teodorescu, Alexandra Cornelia; Forna, Norina Consuela; Agop-Forna, Doriana; Lazar, Ana Petra; Iacob, Maria; Amarie, Teofana; Solomon, Sorina Mihaela

doi:10.3390/biomedicines14061272

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Salivary NETosis-Related and Oxidative Stress Biomarkers Define a Conventional Cigarette Smoking-Associated Inflammatory Phenotype in Periodontitis: A Cross-Sectional Observational Study

by

Irina-Georgeta Sufaru

¹

,

Luminita Lazar

^2,*

,

Alexandra Cornelia Teodorescu

^1,*

,

Norina Consuela Forna

¹,

Doriana Agop-Forna

¹,

Ana Petra Lazar

³,

Maria Iacob

¹,

Teofana Amarie

¹ and

Sorina Mihaela Solomon

¹

Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania

²

George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Department of Periodontology, 540139 Targu Mures, Romania

³

George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Department of Oral Rehabilitation and Occlusology, 540139 Targu Mures, Romania

^*

Authors to whom correspondence should be addressed.

Biomedicines 2026, 14(6), 1272; https://doi.org/10.3390/biomedicines14061272

Submission received: 8 May 2026 / Revised: 28 May 2026 / Accepted: 1 June 2026 / Published: 2 June 2026

(This article belongs to the Special Issue Periodontal Disease and Periodontal Tissue Regeneration—Second Edition)

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Abstract

Background/Objectives: Cigarette smoking is a major risk factor for periodontitis, but the salivary host-response profile associated with smoking-related periodontal inflammation remains incompletely characterized. This study compared salivary NETosis-related and oxidative-inflammatory biomarkers among current smokers, former smokers, and never-smokers with periodontitis. Methods: This cross-sectional study included 159 systemically healthy adults with periodontitis (53 per group: current smokers, former smokers, never-smokers). Individuals with systemic diseases or concomitant medications that could interfere were excluded. Unstimulated whole saliva was analyzed for NETosis-related biomarkers (MPO-DNA complexes, citrullinated histone H3, neutrophil elastase, cell-free DNA) and oxidative-inflammatory markers (MMP-8, IL-1β, IL-6, TNF-α, 8-OHdG, total antioxidant capacity). Results: Salivary MPO-DNA complexes differed significantly among groups (current smokers 33.52 ± 9.96, former smokers 26.90 ± 8.38, never-smokers 19.20 ± 7.50 ng/mL; p < 0.001, η² = 0.317). The composite NETosis score (η² = 0.702) and oxidative-inflammatory score (η² = 0.718) showed the same graded pattern. Biochemical verification confirmed clear group separation (salivary cotinine: current smokers 312.3 ± 77.0, former smokers 9.7 ± 5.1, never-smokers 3.2 ± 1.4 ng/mL). Smoking exposure was positively correlated with biomarker levels and the severity of periodontal disease. Smoking status remained independently associated with MPO-DNA complexes and the NETosis score after covariate adjustment. Conclusions: Current smoking was associated with an enhanced salivary NETosis-related and oxidative-inflammatory phenotype. Former smokers displayed an intermediate profile. Salivary MPO-DNA complexes and composite biomarker scores warrant further investigation as candidate non-invasive indicators of smoking-associated periodontal inflammatory burden, pending diagnostic performance analyses and prospective validation.

Keywords: periodontitis; cigarette smoking; NETosis; salivary biomarkers; oxidative stress; MPO-DNA complexes

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MDPI and ACS Style

Sufaru, I.-G.; Lazar, L.; Teodorescu, A.C.; Forna, N.C.; Agop-Forna, D.; Lazar, A.P.; Iacob, M.; Amarie, T.; Solomon, S.M. Salivary NETosis-Related and Oxidative Stress Biomarkers Define a Conventional Cigarette Smoking-Associated Inflammatory Phenotype in Periodontitis: A Cross-Sectional Observational Study. Biomedicines 2026, 14, 1272. https://doi.org/10.3390/biomedicines14061272

AMA Style

Sufaru I-G, Lazar L, Teodorescu AC, Forna NC, Agop-Forna D, Lazar AP, Iacob M, Amarie T, Solomon SM. Salivary NETosis-Related and Oxidative Stress Biomarkers Define a Conventional Cigarette Smoking-Associated Inflammatory Phenotype in Periodontitis: A Cross-Sectional Observational Study. Biomedicines. 2026; 14(6):1272. https://doi.org/10.3390/biomedicines14061272

Chicago/Turabian Style

Sufaru, Irina-Georgeta, Luminita Lazar, Alexandra Cornelia Teodorescu, Norina Consuela Forna, Doriana Agop-Forna, Ana Petra Lazar, Maria Iacob, Teofana Amarie, and Sorina Mihaela Solomon. 2026. "Salivary NETosis-Related and Oxidative Stress Biomarkers Define a Conventional Cigarette Smoking-Associated Inflammatory Phenotype in Periodontitis: A Cross-Sectional Observational Study" Biomedicines 14, no. 6: 1272. https://doi.org/10.3390/biomedicines14061272

APA Style

Sufaru, I.-G., Lazar, L., Teodorescu, A. C., Forna, N. C., Agop-Forna, D., Lazar, A. P., Iacob, M., Amarie, T., & Solomon, S. M. (2026). Salivary NETosis-Related and Oxidative Stress Biomarkers Define a Conventional Cigarette Smoking-Associated Inflammatory Phenotype in Periodontitis: A Cross-Sectional Observational Study. Biomedicines, 14(6), 1272. https://doi.org/10.3390/biomedicines14061272

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Salivary NETosis-Related and Oxidative Stress Biomarkers Define a Conventional Cigarette Smoking-Associated Inflammatory Phenotype in Periodontitis: A Cross-Sectional Observational Study

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