A Dual Zinc plus Arginine formulation protects against tumor necrosis factor-alpha-induced barrier dysfunction and enhances cell proliferation and migration in an in vitro gingival keratinocyte model

Arch Oral Biol. 2021 Jun:126:105126. doi: 10.1016/j.archoralbio.2021.105126. Epub 2021 Apr 10.

Abstract

Objective: To investigate the effects of Dual Zinc plus Arginine formulations (aqueous solution and dentifrice) on tumor necrosis factor-alpha (TNF-α)-induced barrier dysfunction as well as on cell proliferation and migration in an in vitro gingival keratinocyte model.

Design: Gingival keratinocytes were seeded onto the membrane of a double-chamber system in the absence and presence of recombinant TNF-α and the formulations under investigation. The barrier function was assessed by determination of transepithelial electrical resistance (TER) and paracellular transport of fluorescein isothiocyanate (FITC)-dextran. The distribution of zonula occludens-1 (ZO-1) and occludin was visualized by immunofluorescence microscopy. The effects of the formulations on keratinocyte cell proliferation were determined using a fluorescent cell tracker dye, while a migration assay kit was used to investigate their effects on cell migration.

Results: Under conditions where TNF-α induces loss of keratinocyte barrier integrity, the Dual Zinc plus Arginine formulations (aqueous solution and dentifrice) protected the keratinocyte tight junction against the damages since they prevented the TNF-α-induced drop in TER and increase in FITC-dextran paracellular flux in the in vitro model. The treatment of keratinocytes with the formulations markedly mitigated the altered distribution of ZO-1 and occludin. Both formulations increased the proliferation of keratinocytes and alleviated the negative impact caused by TNF-α. Lastly, the formulations increased the migration capacity of keratinocytes.

Conclusions: The ability of the Dual Zinc plus Arginine formulations to protect the barrier integrity of gingival keratinocytes from TNF-α-induced damage and to promote their proliferation and migration suggests that they may offer benefits for oral health.

Keywords: Arginine; Epithelial barrier; Keratinocyte; Periodontal disease; TNF-α; Toothpaste.

MeSH terms

  • Arginine* / pharmacology
  • Cell Proliferation
  • Intestinal Mucosa
  • Keratinocytes
  • Tumor Necrosis Factor-alpha*
  • Zinc

Substances

  • Tumor Necrosis Factor-alpha
  • Arginine
  • Zinc