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The relative importance of environmental hypoxia due to global climate change on organismal ability to adapt to chemical insult and/or mechanisms of these responses is not well understood. Therefore, we have studied the effects of combined exposure to perfluorooctane sulfonamide (PFOSA) and chemically induced hypoxia on membrane lipid profile and homeostasis. Primary salmon hepatocytes were exposed to PFOSA at 0, 25 and 50 µM singly or in combination with either cobalt chloride (CoCl2: 0 and 150 µM) or deferroxamine (DFO: 0 and 100 µM) for 24 and 48 h. CoCl2 and DFO were used to induce cellular hypoxia because these two chemicals have been commonly used in animal experiments for this purpose and have been shown to increase hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF) levels. Fatty acid (FA) profiles were determined by GC-MS, while gene expression patterns were determined by quantitative PCR. Hypoxic condition was confirmed with time-related increases of HIF-1α mRNA levels in CoCl2 and DFO exposed cells. In general, significant alterations of genes involved in lipid homeostasis were predominantly observed after 48 h exposure. Gene expression analysis showed that biological responses related to peroxisome proliferation (peroxisome proliferator-activated receptors (PPARs) and acyl coenzyme A (ACOX)) and FA desaturation (Δ5- and Δ6-desaturases: FAD5 and FAD6, respectively) and elongation (FAE) were elevated slightly by single exposure (i.e. either PFOSA, CoCl2 or DFO exposure alone), and these responses were potentiated in combined exposure conditions. Principal component analysis (PCA) showed a clustering of peroxisome proliferation responses at transcript levels and FA desaturation against membrane FAs levels whose changes were explained by PFOSA and chemically induced hypoxia exposures. Overall, our data show that most of the observed responses were stronger in combined stressor exposure conditions, compared to individual stressor exposure. In general, our data show that hypoxia may, singly or in combination with PFOSA produce deleterious health, physiological and developmental consequences through the alteration of membrane lipid profile in organisms.

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.

Considerable attention has been given in recent years to the possibility that xenobiotics in the environment may affect reproduction in animals. In this study, the relative impact of tributyltin(IV) (TBT) chloride, one of the most toxic environmental pollutants, was investigated using Ciona intestinalis ovary as a model system. The pleiotropic effects of TBT exposure are concentration dependent and include a decrease of ATP levels, lipid content and nucleic acid content and synthesis. In contrast, a marked increase in calcium (Ca2+) and glucose content is observed. Furthermore, TBT alters enzymatic activity, inhibiting creatine kinase and stimulating alkaline phosphatase and cholinesterase (at concentrations higher than 10−5M in sterile sea water solution). The implications of these effects on reproduction and embryonal development are discussed, along with the possibility that they reflect an extreme cellular defence mechanism triggered to avoid deleterious consequences for the survival of the species.Copyright © 2001 John Wiley & Sons, Ltd.

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