Effects of Carpobrotus edulis Extract on Oxidative Stress and 158N Oligodendrocyte Death.

OBJECTIVE: Age-related diseases, including neurodegenerative diseases, are associated with oxidative stress and lipid peroxidation, and increase the levels of cholesterol auto-oxidation products such as 7ß-hydroxycholesterol (7ß-OHC). Thus, it is imperative to identify agents that can prevent 7ß-OHC-induced side-effects. METHODS: We evaluated the potential protective effects of Carpobrotus edulis ethanol-water extract (EWe) on murine oligodendrocytes (158N) cultured in the absence or presence of 7ß-OHC (20 µg/mL, 24 h). The cells were incubated with EWe (20-200 µg/mL) 2 h before 7ß-OHC treatment. Mitochondrial activity and cell growth were evaluated with the MTT assay. Photometric methods were used to analyze antioxidant enzyme [catalase (CAT) and glutathione peroxidase (GPx)] activities and the generation of lipid and protein oxidation products [malondialdehyde (MDA), conjugated diene (CD), and carbonylated proteins (CPs)]. RESULTS: Treatment with 7ß-OHC induced cell death and oxidative stress (reflected by alteration in CAT and SOD activities). Overproduction of lipid peroxidation products (MDA and CDs) and CPs was also reported. The cytotoxic effects associated with 7ß-OHC were attenuated by 160 µg/mL of EWe of C. edulis. Cell death induced by 7ß-OHC treatment was ameliorated, GPx and CAT activities were restored to normal, and MDA, CD, and CP levels were reduced following C. edulis extract treatment. CONCLUSION: These data demonstrate the protective activities of C. edulis EWe against 7ß-OHC-induced disequilibrium in the redox status of 158N cells, indicative of the potential role of this plant extract in the prevention of neurodegenerative diseases.

Biotin attenuation of oxidative stress, mitochondrial dysfunction, lipid metabolism alteration and 7ß-hydroxycholesterol-induced cell death in 158N murine oligodendrocytes.

Mitochondrial dysfunction and oxidative stress are involved in neurodegenerative diseases associated with an enhancement of lipid peroxidation products such as 7ß-hydroxycholesterol (7ß-OHC). It is, therefore, important to study the ability of 7ß-OHC to trigger mitochondrial defects, oxidative stress, metabolic dysfunctions and cell death, which are hallmarks of neurodegeneration, and to identify cytoprotective molecules. The effects of biotin were evaluated on 158N murine oligodendrocytes, which are myelin synthesizing cells, exposed to 7ß-OHC (50 µM) with or without biotin (10 and 100 nM) or α-tocopherol (positive control of cytoprotection). The effects of biotin on 7ß-OHC activities were determined using different criteria: cell adhesion; plasma membrane integrity; redox status. The impact on mitochondria was characterized by the measurement of transmembrane mitochondrial potential (ΔΨm), reactive oxygen species (ROS) overproduction, mitochondrial mass, quantification of cardiolipins and organic acids. Sterols and fatty acids were also quantified. Cell death (apoptosis, autophagy) was characterized by the enumeration of apoptotic cells, caspase-3 activation, identification of autophagic vesicles, and activation of LC3-I into LC3-II. Biotin attenuates 7ß-OHC-induced cytotoxicity: loss of cell adhesion was reduced; antioxidant activities were normalized. ROS overproduction, protein and lipid oxidation products were decreased. Biotin partially restores mitochondrial functions: attenuation of the loss of ΔΨm; reduced levels of mitochondrial O2•- overproduction; normalization of cardiolipins and organic acid levels. Biotin also normalizes cholesterol and fatty acid synthesis, and prevents apoptosis and autophagy (oxiapoptophagy). Our data support that biotin, which prevents oligodendrocytes damages, could be useful in the treatment of neurodegeneration and demyelination.

Effects of Carpobrotus edulis Extract on Oxidative Stress and 158N Oligodendrocyte Death / 生物医学与环境科学（英文）

OBJECTIVE@#Age-related diseases, including neurodegenerative diseases, are associated with oxidative stress and lipid peroxidation, and increase the levels of cholesterol auto-oxidation products such as 7β-hydroxycholesterol (7β-OHC). Thus, it is imperative to identify agents that can prevent 7β-OHC-induced side-effects.@*METHODS@#We evaluated the potential protective effects of Carpobrotus edulis ethanol-water extract (EWe) on murine oligodendrocytes (158N) cultured in the absence or presence of 7β-OHC (20 μg/mL, 24 h). The cells were incubated with EWe (20-200 µg/mL) 2 h before 7β-OHC treatment. Mitochondrial activity and cell growth were evaluated with the MTT assay. Photometric methods were used to analyze antioxidant enzyme [catalase (CAT) and glutathione peroxidase (GPx)] activities and the generation of lipid and protein oxidation products [malondialdehyde (MDA), conjugated diene (CD), and carbonylated proteins (CPs)].@*RESULTS@#Treatment with 7β-OHC induced cell death and oxidative stress (reflected by alteration in CAT and SOD activities). Overproduction of lipid peroxidation products (MDA and CDs) and CPs was also reported. The cytotoxic effects associated with 7β-OHC were attenuated by 160 μg/mL of EWe of C. edulis. Cell death induced by 7β-OHC treatment was ameliorated, GPx and CAT activities were restored to normal, and MDA, CD, and CP levels were reduced following C. edulis extract treatment.@*CONCLUSION@#These data demonstrate the protective activities of C. edulis EWe against 7β-OHC-induced disequilibrium in the redox status of 158N cells, indicative of the potential role of this plant extract in the prevention of neurodegenerative diseases.

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

Some oxysterols resulting either from enzymatic oxidation or autoxidation of cholesterol are associated with age-related diseases including neurodegenerative diseases. Among these oxysterols, 7ß-hydroxycholesterol (7ß-OHC) is often found at increased levels in patients. It is therefore important to identify molecules or mixtures of molecules to prevent 7ß-OHC-induced side effects. Consequently, murine oligodendrocytes (158N) were cultured in the absence or presence of 7ß-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 7ß-OHC-induced side effects. To this end, the oil (160 µg/mL) was added to the culture medium of 158N cells 2 h before 7ß-OHC. The effects of 7ß-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 7ß-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 7ß-OHC-induced cytotoxicity: 7ß-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 7ß-OHC, similar fatty acid profiles were found in control cells and in cells cultured with 7ß-OHC associated with sea urchin egg oil. These data demonstrate the protective activities of sea urchin egg oil against 7ß-OHC-induced side effects on 158N cells, supporting the concept that this oil may have benefits in the prevention of neurodegenerative diseases.