Antioxidants (Jan 2023)

Mitochondrial and Redox Changes in Periodontitis and Type 2 Diabetes Human Blood Mononuclear Cells

  • Ildete L. Ferreira,
  • Solange Costa,
  • Bruno J. Moraes,
  • Ana Costa,
  • Olga Fokt,
  • Daniela Marinho,
  • Vera Alves,
  • Isabel P. Baptista,
  • A. Cristina Rego

DOI
https://doi.org/10.3390/antiox12020226
Journal volume & issue
Vol. 12, no. 2
p. 226

Abstract

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Periodontitis (PDT) and type 2 diabetes (T2D) have demonstrated a bidirectional relationship and imbalanced oxidative stress linked to mitochondrial dysfunction. Therefore, we investigated mitochondrial and redox (de)regulation in peripheral blood mononuclear cells (PBMCs) in comorbid T2D-PDT, compared to PDT, T2D patients, and control individuals. PBMCs were analyzed for mitochondrial respiration, reactive oxygen species, antioxidant proteins, and expression of Nrf2-target genes. PDT and T2D-PDT patients exhibited altered periodontal clinical markers, while T2D and T2D-PDT patients displayed increased blood HbA1c. Decreased oxygen consumption and ATP production were observed in the PDT patient’s PBMCs. PDT and T2D-PDT PBMCs also evidenced increased H2O2 levels and reduced catalase levels (also detected in T2D patients), whereas a compromised glutathione cycle was observed in T2D-PDT patients. PBMCs from both T2D or T2D-PDT patients showed increased Nrf2 protein levels, enhanced GCL activity and GCL-catalytic subunit protein levels, and maintained GCLc, GST, and HO-1 mRNA levels. In contrast, the expressions of Nrf2-target genes were significantly diminished in the PDT patient’s PBMCs. Decreased SOD1 and GST mRNA levels were also observed in CD3+CD8+-lymphocytes derived from PDT and T2D-PDT patients. In conclusion, PBMCs from T2D-PDT patients showed major redox changes, while mononuclear cells from PDT patients showed mitochondrial deregulation and reduced expression of Nrf2-target genes.

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