The role of transcription factor Nrf2 in the toxicity of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in C57BL/6 mouse astrocytes

Autor: Diane Hardej, Saif A. Alharthy
Rok vydání: 2021
Předmět:
medicine.medical_specialty
NF-E2-Related Factor 2
Health
Toxicology and Mutagenesis
Apoptosis
010501 environmental sciences
Toxicology
medicine.disease_cause
environment and public health
01 natural sciences
Lipid peroxidation
03 medical and health sciences
chemistry.chemical_compound
Lactate dehydrogenase
Internal medicine
medicine
Animals
Cells
Cultured
030304 developmental biology
0105 earth and related environmental sciences
Mice
Knockout
Pharmacology
chemistry.chemical_classification
Fluorocarbons
0303 health sciences
Reactive oxygen species
L-Lactate Dehydrogenase
General Medicine
Glutathione
respiratory system
Mice
Inbred C57BL
Oxidative Stress
Perfluorooctane
Endocrinology
Alkanesulfonic Acids
chemistry
Astrocytes
Toxicity
Perfluorooctanoic acid
Caprylates
Reactive Oxygen Species
Oxidative stress
Zdroj: Environmental Toxicology and Pharmacology. 86:103652
ISSN: 1382-6689
DOI: 10.1016/j.etap.2021.103652
Popis: 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.
Databáze: OpenAIRE
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