Oxidative stress caused by a low concentration of hydrogen peroxide induces senescence-like changes in mouse gingival fibroblasts

Abstract

Periodontal tissue deteriorates under persistent oxidative stress induced by inflammatory reactions in the microflora of the oral cavity. This study aimed to evaluate the cellular properties of mouse gingival fibroblasts (MGFs) in the presence of oxidative stress. MGFs from 10-, 30- and 52-week-old mice were used to evaluate the changes in the cellular properties with aging. The study investigated the effects of oxidative stress on the cellular properties of MGFs from 10-week-old mice. The expression of p53, p21 and murine double minute 2 (Mdm2) in the MGFs in response to oxidative stress was also examined. By day 8, the number of MGFs increased in culture. However, the increase was markedly lower in MGFs derived from aged mice. Oxidative stress due to hydrogen peroxide (H2O2)-induced morphological changes characterized by a round shape with enlarged nuclei and expanded cytoplasm. The cell number of MGFs was decreased subsequent to treatment with 50 μM or a higher concentration of H2O2. MGFs treated with H2O2 at 20 μM showed a similar cell growth curve as the one seen in 52-week-old mice. Phosphorylated p53 protein was increased in MGFs subsequent to treatment with 20 μM H2O2, along with an upregulated transcription of p21 and Mdm2 mRNAs. These results suggest that treatment with a lower concentration of H2O2 in MGFs induces cell cycle arrest, resulting in stress-induced premature senescence, possibly correlated with the development of periodontal diseases.

H2O2 activates matrix metalloproteinases through the nuclear factor kappa B pathway and Ca2+ signals in human periodontal fibroblasts

“…Previous works indicate that exogenous H 2 O 2 generates intracellular Ca 2+ signals and activation of transcription factors, including NFjB in rat nervous cells and human dermal fibroblasts; however, a high variability of responses has been reported according to cell type (23)(24)(25). Accordingly, H 2 O 2 induced Ca 2+ -dependent signaling at concentrations similar to this study in osteoclast-like cells (5), whereas concentrations from 20 lM induced senescence of gingival fibroblasts from mice (26).…”

Cytotoxic Effects of Hydrogen Peroxide on Human Gingival Fibroblasts In Vitro

“…Gingival fibroblasts are known to be affected by H 2 O 2 . 32,33 However, studies have shown that fibroblasts in other parts of the body are more strongly affected. 34 In the present study, highly concentrated H 2 O 2 caused inflammation in gingival fibroblasts and had toxic effects, with marked changes in cell morphology.…”

The impact of antioxidant agents complimentary to periodontal therapy on oxidative stress and periodontal outcomes: A systematic review

“…2,3 Recently, studies have pointed to oxidative stress as being part of the pathogenesis of periodontal diseases. 4 Oxidative stress is a condition caused by a harmful increase in the production of reactive oxygen species (ROS), 5 which are important signalling molecules in the regulation of several cellular processes, 6 emerging when there is an imbalance between ROS levels and the host antioxidant defences. Consequences of the oxidative stress include adaptation, damage or cell death 7 through a variety of mechanisms, such as DNA, lipid and protein damage.…”