Radical-scavenging and Pro-/anti-inflammatory Activity of Tetracycline and Related Phenolic Compounds With or Without Visible Light Irradiation

In Vivo. 2020 Jan-Feb;34(1):81-94. doi: 10.21873/invivo.11748.

Abstract

Background/aim: Microbial tetracycline (TC) pastes have been employed to treat oral bacterial infection. In the present study, we investigated the kinetic radical-scavenging and pro-/anti-inflammatory activity of TC with or without visible light irradiation (VLI).

Materials and methods: The radical-scavenging activity of TC and minocycline (MC) was determined by differential scanning calorimetry (DSC). The stoichiometric factor (n) and the rate constant of inhibition and propagation (kinh/kp) were determined. The levels of cyclooxygenase-2 (Cox2), tumor necrosis factor-α (Tnfα) or nitric oxide synthase 2 (Nos2) mRNA in RAW264.7 cells stimulated with lipopolysaccharide (LPS) were investigated using real-time reverse transcriptase-polymerase chain reaction.

Results: The n and kinh/kp values for 1 mM TC in 2,2'-azobisisobutyronitrile and benzoyl peroxide systems were 0.1-0.2 and 119-250, respectively, whereas the corresponding values for quercetin (QU) and resveratrol (RE) were 2-4 and 7-15, respectively. In RAW264.7 cells stimulated with LPS, Cox2 and Tnfα mRNA were over-expressed in the presence of TC. MC down-regulated only the expression of Cox2 by about 50% in LPS-stimulated cells. The anti-inflammatory activity determined on the basis of Cox2 inhibition declined in the order QU>RE>MC>TC. Upon application of VLI, only TC down-regulated the expression of LPS-stimulated Cox2 and Tnfα mRNA. After exposure to VLI, TC, but not MC, markedly up-regulated hemoxygenase-1 (Ho-1) expression.

Conclusion: TC is a chain-breaking antioxidant with a large kinh Upon activation by VLI, TC may undergo degradation and its degradation products affect pleiotropic mediators such as Cox2, Tnfα and Ho-1. TC may be useful as a local photodynamic therapy for periodontal diseases.

Keywords: Cox2; Ho-1; LPS; Nos2; RAW264.7 cell; Radical-scavenging activity; Tnfα; tetracyclines; visible light.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / metabolism
  • Cell Line
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Down-Regulation / drug effects
  • Free Radical Scavengers / pharmacology
  • Heme Oxygenase-1 / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Nitric Oxide Synthase Type II / metabolism
  • Periodontal Diseases / chemically induced
  • Periodontal Diseases / drug therapy
  • Periodontal Diseases / metabolism
  • Phenols / pharmacology*
  • Quercetin / pharmacology
  • RAW 264.7 Cells
  • RNA, Messenger / metabolism
  • Resveratrol / pharmacology
  • Tetracyclines / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / drug effects

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents
  • Antioxidants
  • Cyclooxygenase 2 Inhibitors
  • Free Radical Scavengers
  • Lipopolysaccharides
  • Phenols
  • RNA, Messenger
  • Tetracyclines
  • Tumor Necrosis Factor-alpha
  • Quercetin
  • Nitric Oxide Synthase Type II
  • Heme Oxygenase-1
  • Cyclooxygenase 2
  • Resveratrol