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-κB. In contrast, Nrf2 was downregulated associated with an elevation in glycogen synthase kinase 3 beta (GSK-3β) and peroxisome proliferator-activated receptor alpha (PPARα). 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.

中文翻译：

---

最佳高氧暴露（40％氧合）对人角质形成细胞中苯并[a] py诱导的毒性的排毒作用。

使用苯并[a] effects（B [a] P）处理的HaCat细胞（人角质形成细胞）作为模型药物在皮肤中引起不良反应，对高氧血症的排毒作用进行了临床研究。众所周知，B [a] P可能产生毒性，包括癌症，内分泌干扰以及涉及DNA损伤，自由基生成和核因子红系2相关因子2（Nrf2）下调的光毒性。众所周知，Nrf2与在高氧（40％氧合）条件下用B [a] P处理的HaCat细胞中抗氧化酶过氧化氢酶（CAT）或解毒酶谷胱甘肽S-转移酶（GST）的增加有关。为了进一步检查该现象的潜在基础，确定了影响Nrf2表达的因素。Nrf2上调伴随p38 MAPK，sequestosome-1（也称为p62）和NF-κB的升高。相反，Nrf2的下调与糖原合酶激酶3β（GSK-3β）和过氧化物酶体增殖物激活的受体α（PPARα）升高有关。还发现高氧血症可减少B [a] P处理的细胞中的DNA损伤和自由基的产生，这归因于Nrf2的显着升高，从而导致抗氧化剂活性或排毒蛋白（包括血红素加氧酶1（HO-1））升高。 ，超氧化物歧化酶（SOD），谷胱甘肽过氧化物酶-1/2（GPX-1 / 2），CAT，GST和谷胱甘肽（GSH）。另外，与皮肤老化有关的因素也因高氧而改变。