Perfluorooctane Sulfonamide-Mediated Modulation of Hepatocellular Lipid Homeostasis and Oxidative Stress Responses in Atlantic Salmon Hepatocytes

• Published in: Chemical research in toxicology Vol. 25; no. 6; pp. 1253 - 1264
• Main Authors: Wågbø, Ane Marit, Cangialosi, Maria V, Cicero, Nicola, Letcher, Robert J, Arukwe, Augustine
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18.06.2012
• Subjects: Animals; Dose-Response Relationship, Drug; Fluorocarbons - pharmacology; Hepatocytes - drug effects; Hepatocytes - metabolism; Homeostasis - drug effects; Lipid Metabolism - drug effects; Oxidative Stress - drug effects; Salmo salar; Structure-Activity Relationship; Sulfonamides - pharmacology
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/tx300110u

We have investigated the effects of perfluorooctane sulfonamide (PFOSA) on cellular functions and lipid homeostasis (including β-oxidation) in salmon primary hepatocytes. Salmon hepatocytes were exposed to PFOSA at 0 (control), 2, 20, and 50 μM for 12 and 24 h. Fatty acids (FAs) and lipids were determined by GC-MS; FA elongase (FAE), Δ5-desaturase (FAD5), Δ6-desaturase (FAD6), peroxisome proliferator-activated receptors (PPARs), acyl coenzyme A (ACOX-1), glutathione peroxidase (GPx), catalase (CAT), and glutathione S-transferase (GST) mRNA were analyzed using qPCR. GST activity was analyzed by biochemical assays using 1-chloro-2,4-dinitrobenzene (CDNB) as substrate. Our data showed that PFOSA produced significant changes in FA composition that predominantly involved a decrease (at 12 h) and an increase (at 24 h) in FA methyl esters (FAMEs), MUFA, total PUFA, and (n-3 and n-6) PUFA. Particularly, an increase of α-linolenic acid (ALA; 18:3n-3), eicosapentaenoic acid [EPA; 20:5n-3], and arachidonic acid [ARA: 20:4n-6] with associated increase in FAE, FAD5, and FAD6 mRNA were observed after PFOSA exposure, while cis-13,16-docosadienoic acid (22:2) was significantly decreased. PFOSA produced apparent concentration-dependent increase of PPARα and PPARγ. CAT, GPx, and GST mRNA show that PFOSA produced concentration- and time-specific increase of CAT and GST, but no changes in GST activity were observed. In general, these responses indicate that PFOSA evokes deleterious effects on cellular lipid homeostasis and transcriptional responses that regulate cellular oxidative homeostasis in salmon hepatocytes.