Protective Effect of Baicalein on Oxidative Stress-induced DNA Damage and Apoptosis in RT4-D6P2T Schwann Cells

Int J Med Sci. 2019 Jan 1;16(1):8-16. doi: 10.7150/ijms.29692. eCollection 2019.

Abstract

Background: Due to its high antioxidant activity, baicalein, a kind of flavonoid present in Radical Scutellariae, has various pharmacological effects. However, the protective effect against oxidative stress in Schwann cells, which plays an important role in peripheral neuropathy, has not yet been studied. In this study, the effects of baicalein on hydrogen peroxide (H2O2)-induced DNA damage and apoptosis in RT4-D6P2T Schwann cells were evaluated. Methods: Cell viability assay was performed using MTT assay and colony formation assay. Apoptosis was assessed by flow cytometry analysis and DNA fragmentation assay. The effects on DNA damage and ATP content were analyzed by comet method and luminometer. In addition, changes in protein expression were observed by Western blotting. Results: Our results show that baicalein significantly inhibits H2O2-induced cytotoxicity through blocking reactive oxygen species (ROS) generation. We also demonstrate that baicalein is to block H2O2-induced DNA damage as evidenced by inhibition of DNA tail formation and γH2AX phosphorylation. Moreover, baicalein significantly attenuated H2O2-induced apoptosis and mitochondrial dysfunction, and restored inhibition of ATP production. The suppression of apoptosis by baicalein in H2O2-stimulated cells was associated with reduction of increased Bax/Bcl-2 ratio, activation of caspase-9 and -3, and degradation of poly (ADP-ribose) polymerase. Conclusions: These results demonstrate that baicalein eliminates H2O2-induced apoptosis through conservation of mitochondrial function by the removal of ROS. Therefore, it is suggested that baicalein protects Schwann cells from oxidative stress, and may be beneficial for the prevention and treatment of peripheral neuropathy induced by oxidative stress.

Keywords: Baicalein; DNA damage; Schwann cells; apoptosis; oxidative stress.

MeSH terms

  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Cell Survival / drug effects
  • DNA Damage / drug effects*
  • Energy Metabolism / drug effects
  • Flavanones / pharmacology*
  • Flavanones / therapeutic use
  • Gene Expression Regulation
  • Genes, bcl-2
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Oxidants / pharmacology
  • Oxidative Stress / drug effects*
  • Peripheral Nervous System Diseases / drug therapy
  • Peripheral Nervous System Diseases / metabolism
  • Reactive Oxygen Species / antagonists & inhibitors
  • Schwann Cells / physiology*
  • Schwann Cells / ultrastructure
  • bcl-2-Associated X Protein

Substances

  • Antioxidants
  • Flavanones
  • Oxidants
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • baicalein
  • Hydrogen Peroxide