Detoxifying effects of optimal hyperoxia (40% oxygenation) exposure on benzo[a]pyrene-induced toxicity in human keratinocytes
- Authors
- Kwon, Yong Chan; Kim, Hyung Sik; Lee, Byung-Mu
- Issue Date
- Jan-2020
- Publisher
- TAYLOR & FRANCIS INC
- Keywords
- Optimal hyperoxia; detoxification; benzo[a]pyrene; oxygen; Nrf2; antioxidant
- Citation
- JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, v.83, no.2, pp 82 - 94
- Pages
- 13
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES
- Volume
- 83
- Number
- 2
- Start Page
- 82
- End Page
- 94
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/7620
- DOI
- 10.1080/15287394.2020.1730083
- ISSN
- 1528-7394
1087-2620
- Abstract
- Detoxifying effects of hyperoxia, which is widely used in clinical practice, were investigated using HaCat cells (human keratinocytes) treated with benzo[a]pyrene (B[a]P) as a model agent to induce adverse effects in the skin. It is well-established that B[a]P may produce toxicities including cancer, endocrine disruption, and phototoxicity involving DNA damage, free radical generation, and down regulation of nuclear factor erythroid 2-related factor 2 (Nrf2). It is well-known that Nrf2 is associated increase of antioxidant enzyme catalase (CAT) or detoxification enzyme glutathione S-transferase (GST) in HaCat cells treated with B[a]P under optimal condition of hyperoxia (40% oxygenation) conditions. To further examine the underlying basis of this phenomenon, factors affecting the expression of Nrf2 were determined. Nrf2 was upregulated accompanied by a rise in p38 MAPK, sequestosome-1 (also known as p62) and NF-kappa B. In contrast, Nrf2 was downregulated associated with an elevation in glycogen synthase kinase 3 beta (GSK-3 beta) and peroxisome proliferator-activated receptor alpha (PPAR alpha). Hyperoxia was also found to diminish DNA damage and generation of free radicals initiated in B[a]P-treated cells which was attributed to an significant rise of Nrf2, leading to elevated antioxidant activities or detoxification proteins including heme oxygenase 1 (HO-1), superoxide dismutase (SOD), glutathione peroxidase-1/2 (GPX-1/2), CAT, GST and glutathione (GSH). In addition, factors related to skin aging were also altered by hyperoxia. Data suggest that optimal hyperoxia exposure of 40% oxygenation may reduce cellular toxicity induced by B[a]P in HaCat cells as evidenced by inhibition of DNA damage, free radical generation, and down-regulation of Nrf2.
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Collections - Pharmacy > Department of Pharmacy > 1. Journal Articles
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