7β-hydroxycholesterol-induced cell death, oxidative stress, and fatty acid metabolism dysfunctions attenuated with sea urchin egg oil

Abstract

Some oxysterols resulting either from enzymatic oxidation or autoxidation of cholesterol are associated with age-related diseases including neurodegenerative diseases. Among these oxysterols, 7β-hydroxycholesterol (7β-OHC) is often found at increased levels in patients. It is therefore important to identify molecules or mixtures of molecules to prevent 7β-OHC-induced side effects. Consequently, murine oligodendrocytes (158N) were cultured in the absence or presence of 7β-OHC (20 μg/mL, 24 h) with or without a natural oil extracted from sea urchin (Paracentrotus lividus) eggs known for its biological activity. Firstly, the chemical composition of this oil was determined using ³¹P NMR and GC-MS. Secondly, this oil was used to reduce 7β-OHC-induced side effects. To this end, the oil (160 μg/mL) was added to the culture medium of 158N cells 2 h before 7β-OHC. The effects of 7β-OHC with or without the oil on cell viability were studied with the MTT test. Photometric methods were used to analyze antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPx), as well as the generation of lipid peroxidation products (malondialdehyde (MDA), conjugated dienes (CDs)) and protein oxidation product (carbonylated proteins (CPs)). Gas chromatography was used to determine the fatty acid profile. With 7β-OHC, an induction of cell death associated with oxidative stress (alteration of GPx and SOD activities) was observed; an overproduction of lipid peroxidation products (MDA and CDs) and CPs was also revealed. Sea urchin egg oil attenuated 7β-OHC-induced cytotoxicity: 7β-OHC-induced cell death was reduced, GPx and SOD activities were normalized, and lower levels of MDA, CDs and CPs were produced. In addition, whereas a disturbed fatty acid profile was observed with 7β-OHC, similar fatty acid profiles were found in control cells and in cells cultured with 7β-OHC associated with sea urchin egg oil. These data demonstrate the protective activities of sea urchin egg oil against 7β-OHC-induced side effects on 158N cells, supporting the concept that this oil may have benefits in the prevention of neurodegenerative diseases.

Keywords: 158N oligodendrocytes; 7β-hydroxycholesterol; Antioxidant enzymes; Fatty acid; Lipid peroxidation; Sea urchin egg oil.