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

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.