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) 属于全氟烷基物质 (PFAS)。本研究旨在确定 Nrf2 对这些药物毒性的保护作用。 Nrf2-/-和野生型星形胶质细胞暴露于 PFOS (75−600 μM) 和 PFOA (400−1000 μM) 24 小时。 nrf2 -/- 中的乳酸脱氢酶 (LDH) 释放显着高于野生型星形胶质细胞。与野生型星形胶质细胞相比，暴露于 600 μM PFOS 和 800 μM PFOA 后，nrf2-/-星形胶质细胞中的活性氧、脂质过氧化和细胞凋亡显着增加。与野生型星形胶质细胞相比， nrf2-/-星形胶质细胞的 GSH/GSSG 比率显着降低。此外，全氟辛烷磺酸和全氟辛烷磺酸引起线粒体超微结构的巨大改变。野生型细胞中的 BHT 预处理降低了暴露于这两种试剂的 ROS 产生。本研究的结果得出结论，PFOS 和 PFOA 对星形胶质细胞具有细胞毒性，并且nrf2 -/-细胞对这些药物的毒性更敏感。