Effect of antioxidants on the H2O2-induced premature senescence of human fibroblasts

Abstract

The study was aimed at evaluation of the role of secondary oxidative stress in the stress-induced premature senescence (SIPS) of human fibroblasts induced by H2O2. Two fibroblast lines were used: lung MRC-5 and ear H8F2p25LM fibroblasts. The lines differed considerably in sensitivity to H2O2 (IC50 of 528 and 33.5 µM, respectively). The cells were exposed to H2O2 concentrations corresponding to IC50 and after 24 h supplemented with a range of antioxidants. Most of antioxidants studied slightly augmented the survival of fibroblasts at single concentrations or in a narrow concentration range, but the results were not consistent among the cell lines. Chosen antioxidants (4-amino-TEMPO, curcumin, caffeic acid and p-coumaric acid) did not restore the level of glutathione decreased by H2O2. Hydrogen peroxide treatment did not induce secondary production of H2O2 and even decreased it, decreased mitochondrial potential in both cell lines and induced changes in the mitochondrial mass inconsistent between the lines. Antioxidant protected mitochondrial potential only in H8F2p25LM cells, but attenuated changes in mitochondrial mass. These results speak against the intermediacy of secondary oxidative stress in the SIPS induced by H2O2 and suggest that the small protective action of antioxidants is due to their effects on mitochondria.

The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence

“…It has been shown that p-CA can have beneficial effects on skin aging by decreasing collagenase, elastase, and hyaluronidase activity [ 386 ], and by reducing the inflammatory response and chondrocytes senescence, inhibiting MAPK and NF-kB signalling pathways [ 327 ]. However, although some works have demonstrated the antioxidant property of p-CA, Pieńkowska et al highlighted that this acid is unable to counteract the premature senescence of human fibroblasts [ 387 ]. Consequently, the presence of contradictory evidence in literature requires further research.…”

Preventive Effect of Nuciferine on H2O2-Induced Fibroblast Senescence and Pro-Inflammatory Cytokine Gene Expression

“…The previously published reports demonstrated that the dermal fibroblasts receiving H 2 O 2 underwent G0/G1 arrest. This cellular adaptation was also observed concomitantly with ROS accumulation and oxidation-associated damage [ 10 , 11 ]. In this regard, oxidative stress could result in DNA damage and cell cycle arrest [ 6 ].…”

“…Senescent fibroblast cells have a specifically enlarged cytoplasm, poor response to growth factors, and β-galactosidase activity [ 4 , 23 , 24 ]. The H 2 O 2 , when being exposed to cultured fibroblasts, induces premature senescence by imposing oxidative stress and sustained accumulation of oxidative DNA damage [ 10 , 11 ]. In this study, the preventive ability of nuciferine to mitigate H 2 O 2 -induced premature senescence was assessed.…”

“…The previous seminal studies plausibly explain the mechanistic basis for senescent prevention of nuciferine in the present work. Furthermore, according to recent research on plant extract and inflammation, it has been demonstrated that natural compounds with antioxidant activities can prevent senescent progression by modulating SASP factors and associated genes [ 10 , 14 , 29 ]. Based on the obtained results and previous work, nuciferine could reduce inflammatory mediators and prevent fibroblasts from H 2 O 2 toxicity.…”

“…The impact of various senescence-inducing stress signals and the strategies to circumvent them have been an important area of focus in aging skin research [ 9 ]. Several lines of evidence suggest that hydrogen peroxide (H 2 O 2 ) induces fibroblast senescence and subsequent cell death [ 10 , 11 ]. The H 2 O 2 is experimentally used to study oxidative-stress-induced premature senescence within a short period of time.…”