Gingival Crevicular Fluid and Plasma Levels of Transglutaminase-2 and Oxidative Stress Markers in Cyclosporin A-Induced Gingival Overgrowth

J Periodontol. 2016 Dec;87(12):1508-1516. doi: 10.1902/jop.2016.160031. Epub 2016 Jul 29.

Abstract

Background: Transglutaminase (TGM)-2 has been shown to contribute to fibrosis by extracellular matrix accumulation in some organs and is activated by intracellular reactive oxygen species. The aim of this study is to investigate levels of gingival crevicular fluid (GCF) and plasma TGM-2 and oxidative stress markers (OSMs) in cyclosporin A (CsA)-induced gingival overgrowth (GO).

Methods: The study enrolled 20 healthy (H) individuals; 20 patients with gingivitis (G); 20 CsA-medicated patients with GO (CsA GO+); and 20 CsA-medicated patients without GO (CsA GO-). GCF and plasma levels of TGM-2 were analyzed by enzyme-linked immunosorbent assay. Spectrofluorometry was used to analyze thiobarbituric acid reactive substance (TBARS); ferric-reducing antioxidant power (FRAP); total oxidant status (TOS); and total antioxidant capacity (TAC).

Results: GCF TGM-2 level was elevated in CsA GO+ compared with G (P = 0.048) and H (P = 0.001) groups. GCF TBARS level was elevated in CsA GO+ compared with other groups (CsA GO- group: P = 0.003; G group: P <0.001; and H group: P <0.001) and was higher in CsA GO- than in H (P = 0.048). GCF FRAP level was lower in CsA GO- than in H (P = 0.04). Both CsA GO+ and CsA GO- groups had lower GCF TOS levels than H (P <0.001 and P = 0.002) and G (P = 0.003 and P = 0.04). GCF TAC was higher in CsA GO+ than in H (P = 0.02). Plasma TGM-2 level was elevated in CsA GO+ compared with G (P = 0.048) and H (P = 0.002). Plasma FRAP level was higher in H and CsA GO- than in CsA GO+ (P = 0.008 and P = 0.02).

Conclusions: CsA use significantly alters GCF and plasma levels of TGM-2 and OSMs. TGM-2 may contribute to CsA-induced GO in CsA-treated patients by changing GCF and plasma levels of OSMs. Further studies are needed to prove causality and its direction.

Keywords: Cyclosporine; gingival crevicular fluid; gingival overgrowth; oxidative stress; plasma; transglutaminase 2.

MeSH terms

  • Case-Control Studies
  • Cyclosporine / adverse effects*
  • GTP-Binding Proteins / analysis*
  • Gingival Crevicular Fluid / chemistry*
  • Gingival Overgrowth*
  • Gingivitis
  • Humans
  • Immunosuppressive Agents
  • Kidney Transplantation
  • Oxidative Stress*
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases / analysis*

Substances

  • Immunosuppressive Agents
  • Cyclosporine
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins