Changes in tumor suppressors and inflammatory responses during hydrogen peroxide-induced senescence in rat fibroblasts

Free Radic Res. 2022 Jan;56(1):77-89. doi: 10.1080/10715762.2022.2037582. Epub 2022 Feb 14.

Abstract

Cell proliferation and senescence are processes induced by oxidative stress. In this study, we aimed to establish a cellular model of rapid proliferation and senescence of rat tail-tip fibroblasts by hydrogen peroxide (H2O2), a well-known oxidant. On this basis, changes in oxidative stress, inflammatory response and cell cycle of fibroblasts were studied. After H2O2 treatment, cell counting and flow cytometry results showed that 50 μM of H2O2 for 12 h and 100 μM for 8 h effectively promoted fibroblast proliferation, while 500 μM rapidly led to cell cycle arrest. In addition, stimulation with H2O2 at a concentration of 50 μM also promoted the inflammatory effects of the cells. At a concentration of 100 μM H2O2, the cellular antioxidant system began to collapse at 8 h and began to affect cellular activity. 500 μM of H2O2 at 4 h the levels of senescence-associated β-galactosidase, a marker of senescence and oxidative stress, were almost positive in fibroblasts. In addition, we found that the risk of fibroblasts carcinogenesis increased with increased H2O2 stimulation. The results of this study indicate that H2O2 can cause rapid proliferation and senescence of fibroblasts and that its mechanism of action may be mainly through influencing cellular antioxidant systems, cellular inflammatory responses and cell cycle.

Keywords: H2O2; oxidative stress; proliferation; rat fibroblasts; senescence.

MeSH terms

  • Animals
  • Antioxidants* / metabolism
  • Cellular Senescence
  • Fibroblasts
  • Hydrogen Peroxide* / metabolism
  • Hydrogen Peroxide* / pharmacology
  • Oxidative Stress
  • Rats

Substances

  • Antioxidants
  • Hydrogen Peroxide