Effects of antioxidants and MAPK inhibitors on cell death and reactive oxygen species levels in H2O2-treated human pulmonary fibroblasts
Open accessAbstract
H2O2‑induced cytotoxicity in normal human pulmonary fibroblasts (HPFs) is of interest in toxicological research since HPFs are involved in lung inflammation, fibrosis and cancer. The present study investigated the cytotoxic effects of H2O2 on normal HPFs in relation to reactive oxygen species (ROS) and mitogen‑activated protein kinases (MAPKs) using the well‑known antioxidants N‑acetyl cysteine (NAC) and propyl gallate (PG), as well as MAPK inhibitors. Treatment with 50 µM H2O2 inhibited the growth of the HPFs by ~45% in 24 h. H2O2 induced cell death via apoptosis and triggered the loss of mitochondrial membrane potential (MMP; ∆ψm) in the HPFs. H2O2 also increased the ROS levels, including O2•‑, in the HPFs and induced glutathione (GSH) depletion. NAC and PG attenuated the death of the HPFs and the loss of MMP (∆ψm) through the use of H2O2. NAC decreased the ROS levels in the H2O2‑treated HPFs and PG markedly prevented an increase in O2•‑ levels in these cells. However, PG alone induced cell death in the HPF control cells and increased the ROS levels in these cells. None of the MAPK (MEK, JNK and p38) inhibitors affected cell growth inhibition or cell death by H2O2. In addition, these inhibitors did not significantly affect the ROS levels and GSH depletion in the H2O2‑treated HPFs. In conclusion, H2O2 induced growth inhibition and cell death in the HPFs via GSH depletion. NAC and PG attenuated H2O2‑induced HPF cell death but each regulated the ROS levels in a different manner. Treatment with MAPK inhibitors did not affect cell death or the ROS levels in the H2O2‑treated HPFs.
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UV radiation induces excessive ROS production, which activates the MAPK/AP-1 pathway and stimulates MMP expression, promoting collagen degradation and resulting in skin photoaging.
“Furthermore, ROS can also activate the MAPK/AP-1 pathway and stimulate the expression of MMPs, promoting the degradation of collagen and resulting in skin photoaging [59].”
From Boosting the Photoaged Skin: The Potential Role of Dietary Components (2021) · cites this paper as [59]
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- Authors
- PARK, W. H.
- Affiliations
- Jeonbuk National University (KR)
- Corresponding author
- PARK, WOO HYUN
- ORCID
- PARK, WOO HYUN
- Venue
- Oncology Letters
- Publisher
- Spandidos Publications
- Published
- 2013-02-28
- Volume
- 5
- Issue
- 5
- Pages
- 1633-1638
- ISSN
- 1792-1074 (ISSN-L)
- 1792-1082
- PMC
- PMC3678714
- OpenAlex
- W2071803503
- Cited by
- 23
- References
- 30
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 1 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 2
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Oncology Letters (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Chonbuk National University
- Korea Science and Engineering Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- hydrogen peroxide, lung fibroblasts, reactive oxygen species, antioxidants, N-acetylcysteine, propyl gallate, MAPK inhibitors, apoptosis, mitochondrial membrane potential, glutathione depletion, superoxide, cell death, oxidative stress, MEK, JNK, p38 MAPK
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