Methylparaben‐induced decrease in collagen production and viability of cultured human dermal fibroblasts

Abstract

Parabens owing to their many advantageous properties are widely applied in cosmetics, food products and pharmaceuticals. However, recent research results have shown that they possess the ability to accumulate in the human body and exert many adverse effects. In this study, the impact of methylparaben (MP) as the most frequently used preservative in cosmetics, on human dermal fibroblasts and collagen production was evaluated. In cells treated with 0.01, 0.03 and 0.05% MP a dose-dependent decrease in collagen biosynthesis was revealed, which was positively correlated with the activity of prolidase responsible for the recovery of proline. Consequently, the concentration of total collagen secreted into the medium was markedly diminished. A similar reduction in expression of the major skin collagen type I at both the protein and mRNA level as well as collagen type III and VI at the mRNA level was also detected. The decrease in the collagen level may result not only from the reduced synthesis but also increased degradation owing to MP-induced activation of pro-MMP-2 (72 kDa). The increase in activity of MMP-2 (66 kDa) was accompanied by a reduction in the inhibitory activity of TIMP-2. In addition, an inhibitory effect of MP on cell survival and proliferation was revealed in this study. The increased expression and nuclear translocation of caspase-3 as well as increased Bax and decreased Bcl-2 expression may suggest MP-induced cell apoptosis. In summary, we have provided new data on the adverse effects of methylparaben on human dermal fibroblasts and the main structural protein of the skin. Further studies on the mechanisms responsible for its action are in progress. Copyright © 2017 John Wiley & Sons, Ltd.

Anti‑apoptotic effects of glycosaminoglycans via inhibition of ERK/AP‑1 signaling in TNF‑α‑stimulated human dermal fibroblasts

“…However, the results demonstrated that levels of TIMP-1, an inhibitor of MMP-1, increased along with the concentration of GAGs in HDFs stimulated with TNF-α. The results of the present study therefore support the conclusion that MMPs and TIMPs are directly and indirectly involved in the synthesis of collagen type I (40)(41)(42)(43).…”

“…1). The regulatory proteins of collagen degradation were further assessed as many enzymes, including MMPs and tissue inhibitors of metalloproteinase (TIMPs), are directly and indirectly involved in collagen type I degradation (40)(41)(42)(43). The results demonstrated that GAGs inhibited MMP-1 gene activation ( Fig.…”

The Protective Effect of Rosmarinic Acid against Unfavorable Influence of Methylparaben and Propylparaben on Collagen in Human Skin Fibroblasts

“…Taking into account our previous study on the effect of MP alone on the biosynthesis of collagen in the human skin fibroblasts, it can be concluded that combining these two parabens can intensify the negative effect of MP on this skin protein and on the cellular processes. MP at a concentration 10 times lower than that used in our previous study [28], but in combination with PP (0.001% MP and 0.0003% PP) exerted a similar inhibitory effect (by 32.4%) on this process as 0.01% MP alone (by 27%) [28]. Parabens influenced the biosynthesis of total collagen and the expression of two main types (I and III) of the skin collagen directly at the transcriptional level.…”

“…Our research team previously provided data on the harmful effects of MP alone at concentrations of 0.01%, 0.03%, and 0.05% on the expression of collagen in the human skin fibroblasts [28]. In the present study, to better reflect the real situation of human exposure to parabens, we have used the lowest concentration of MP (0.01%), at which we have noted its unfavorable impact on the skin cells, and two lower concentrations (0.001% and 0.003%).…”

Methylparaben and butylparaben alter multipotent mesenchymal stem cell fates towards adipocyte lineage

“…Although this dose of paraben falls in the range of doses reported for paraben studies in the current literature [14, 57–59], our knowledge about human systemic exposure to parabens remains to be limited. It has been suggested that the levels of paraben detected in human subjects vary depending on the age, gender, and ethnicity, possibly reflecting frequency of exposure, the level of parabens contained in the products, and the percentage of skin areas covered with paraben containing cosmetic products [11, 60].…”