Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY, 11439, USA; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY, 11439, USA.
Environ Toxicol Pharmacol. 2021 Aug;86:103652. doi: 10.1016/j.etap.2021.103652. Epub 2021 Apr 1.
Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are members of perfluoroalkyl substances (PFAS). This study aimed to determine the protective role of Nrf2 against the toxicity of these agents. Nrf2-/- and wild-type astrocytes were exposed to PFOS (75-600 μM) and PFOA (400-1000 μM) for 24 h. Lactate dehydrogenase (LDH) release was significantly higher in nrf2-/- than in the wild-type astrocytes. Exposure to 600 μM PFOS and 800 μM PFOA showed significant increases in reactive oxygen species, lipid peroxidation, and apoptosis in nrf2-/- astrocytes as compared to wild-type astrocytes. The GSH/GSSG ratio was significantly decreased in nrf2-/- astrocytes when compared to wild-type astrocytes. Additionally, PFOS and PFOS caused dramatic ultrastructural alterations to the mitochondria. BHT pretreatment in wild-type cells decreased ROS production with exposure to both agents. Results of the present study conclude that PFOS and PFOA are cytotoxic to astrocytes and that nrf2 -/- cells are more sensitive to toxicity by these agents.
全氟辛烷磺酸（PFOS）和全氟辛酸（PFOA）是全氟烷基物质（PFAS）的成员。本研究旨在确定 Nrf2 对这些物质毒性的保护作用。Nrf2-/-和野生型星形胶质细胞分别暴露于 PFOS（75-600 μM）和 PFOA（400-1000 μM）24 小时。与野生型星形胶质细胞相比，Nrf2-/-星形胶质细胞中乳酸脱氢酶（LDH）的释放明显更高。与野生型星形胶质细胞相比，暴露于 600 μM PFOS 和 800 μM PFOA 可使 Nrf2-/-星形胶质细胞中的活性氧、脂质过氧化和细胞凋亡明显增加。与野生型星形胶质细胞相比，Nrf2-/-星形胶质细胞中的 GSH/GSSG 比值明显降低。此外，PFOS 和 PFOS 导致线粒体的超微结构发生明显改变。在暴露于两种物质时，BHT 预处理可减少野生型细胞中的 ROS 生成。本研究的结果表明，PFOS 和 PFOA 对星形胶质细胞具有细胞毒性，并且 Nrf2-/-细胞对这些物质的毒性更为敏感。
