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7-Ketocholesterol, which is one of the earliest cholesterol oxidization products identified, is essentially formed by the auto-oxidation of cholesterol. In the body, 7-ketocholesterol is both provided by food and produced endogenously. This pro-oxidant and pro-inflammatory molecule, which can activate apoptosis and autophagy at high concentrations, is an abundant component of oxidized Low Density Lipoproteins. 7-Ketocholesterol appears to significantly contribute to the development of age-related diseases (cardiovascular diseases, age-related macular degeneration, and Alzheimer's disease), chronic inflammatory bowel diseases and to certain cancers. Recent studies have also shown that 7-ketocholesterol has anti-viral activities, including on SARS-CoV-2, which are, however, lower than those of oxysterols resulting from the oxidation of cholesterol on the side chain. Furthermore, 7-ketocholesterol is increased in the serum of moderately and severely affected COVID-19 patients. In the case of COVID-19, it can be assumed that the antiviral activity of 7-ketocholesterol could be counterbalanced by its toxic effects, including pro-oxidant, pro-inflammatory and pro-coagulant activities that might promote the induction of cell death in alveolar cells. It is therefore suggested that this oxysterol might be involved in the pathophysiology of COVID-19 by contributing to the acute respiratory distress syndrome and promoting a deleterious, even fatal outcome. Thus, 7-ketocholesterol could possibly constitute a lipid biomarker of COVID-19 outcome and counteracting its toxic effects with adjuvant therapies might have beneficial effects in COVID-19 patients.
Imen Ghzaiel; Khouloud Sassi; Amira Zarrouk; Thomas Nury; Mohamed Ksila; Valerio Leoni; Balkiss Bouhaouala-Zahar; Sonia Hammami; Mohamed Hammami; John J. Mackrill; Mohammad Samadi; Taoufik Ghrairi; Anne Vejux; Gérard Lizard. 7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19. The Journal of Steroid Biochemistry and Molecular Biology 2021, 212, 105939 .
AMA StyleImen Ghzaiel, Khouloud Sassi, Amira Zarrouk, Thomas Nury, Mohamed Ksila, Valerio Leoni, Balkiss Bouhaouala-Zahar, Sonia Hammami, Mohamed Hammami, John J. Mackrill, Mohammad Samadi, Taoufik Ghrairi, Anne Vejux, Gérard Lizard. 7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19. The Journal of Steroid Biochemistry and Molecular Biology. 2021; 212 ():105939.
Chicago/Turabian StyleImen Ghzaiel; Khouloud Sassi; Amira Zarrouk; Thomas Nury; Mohamed Ksila; Valerio Leoni; Balkiss Bouhaouala-Zahar; Sonia Hammami; Mohamed Hammami; John J. Mackrill; Mohammad Samadi; Taoufik Ghrairi; Anne Vejux; Gérard Lizard. 2021. "7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19." The Journal of Steroid Biochemistry and Molecular Biology 212, no. : 105939.
The Mediterranean diet is associated with health benefits due to bioactive compounds such as polyphenols. The biological activities of three polyphenols (quercetin (QCT), resveratrol (RSV), apigenin (API)) were evaluated in mouse neuronal N2a cells in the presence of 7-ketocholesterol (7KC), a major cholesterol oxidation product increased in patients with age-related diseases, including neurodegenerative disorders. In N2a cells, 7KC (50 µM; 48 h) induces cytotoxic effects characterized by an induction of cell death. When associated with RSV, QCT and API (3.125; 6.25 µM), 7KC-induced toxicity was reduced. The ability of QCT, RSV and API to prevent 7KC-induced oxidative stress was characterized by a decrease in reactive oxygen species (ROS) production in whole cells and at the mitochondrial level; by an attenuation of the increase in the level and activity of catalase; by attenuating the decrease in the expression, level and activity of glutathione peroxidase 1 (GPx1); by normalizing the expression, level and activity of superoxide dismutases 1 and 2 (SOD1, SOD2); and by reducing the decrease in the expression of nuclear erythroid 2-like factor 2 (Nrf2) which regulates antioxidant genes. QCT, RSV and API also prevented mitochondrial dysfunction in 7KC-treated cells by counteracting the loss of mitochondrial membrane potential (ΨΔm) and attenuating the decreased gene expression and/or protein level of AMP-activated protein kinase α (AMPKα), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) implicated in mitochondrial biogenesis. At the peroxisomal level, QCT, RSV and API prevented the impact of 7KC by counteracting the decrease in ATP binding cassette subfamily D member (ABCD)3 (a peroxisomal mass marker) at the protein and mRNA levels, as well as the decreased expresssion of genes associated with peroxisomal biogenesis (Pex13, Pex14) and peroxisomal β-oxidation (Abcd1, Acox1, Mfp2, Thiolase A). The 7KC-induced decrease in ABCD1 and multifunctional enzyme type 2 (MFP2), two proteins involved in peroxisomal β-oxidation, was also attenuated by RSV, QCT and API. 7KC-induced cell death, which has characteristics of apoptosis (cells with fragmented and/or condensed nuclei; cleaved caspase-3; Poly(ADP-ribose) polymerase (PARP) fragmentation) and autophagy (cells with monodansyl cadaverine positive vacuoles; activation of microtubule associated protein 1 light chain 3–I (LC3-I) to LC3-II, was also strongly attenuated by RSV, QCT and API. Thus, in N2a cells, 7KC induces a mode of cell death by oxiapoptophagy, including criteria of OXIdative stress, APOPTOsis and autoPHAGY, associated with mitochondrial and peroxisomal dysfunction, which is counteracted by RSV, QCT, and API reinforcing the interest for these polyphenols in prevention of diseases associated with increased 7KC levels.
Aline Yammine; Amira Zarrouk; Thomas Nury; Anne Vejux; Norbert Latruffe; Dominique Vervandier-Fasseur; Mohammad Samadi; John J. Mackrill; Hélène Greige-Gerges; Lizette Auezova; Gérard Lizard. Prevention by Dietary Polyphenols (Resveratrol, Quercetin, Apigenin) Against 7-Ketocholesterol-Induced Oxiapoptophagy in Neuronal N2a Cells: Potential Interest for the Treatment of Neurodegenerative and Age-Related Diseases. Cells 2020, 9, 2346 .
AMA StyleAline Yammine, Amira Zarrouk, Thomas Nury, Anne Vejux, Norbert Latruffe, Dominique Vervandier-Fasseur, Mohammad Samadi, John J. Mackrill, Hélène Greige-Gerges, Lizette Auezova, Gérard Lizard. Prevention by Dietary Polyphenols (Resveratrol, Quercetin, Apigenin) Against 7-Ketocholesterol-Induced Oxiapoptophagy in Neuronal N2a Cells: Potential Interest for the Treatment of Neurodegenerative and Age-Related Diseases. Cells. 2020; 9 (11):2346.
Chicago/Turabian StyleAline Yammine; Amira Zarrouk; Thomas Nury; Anne Vejux; Norbert Latruffe; Dominique Vervandier-Fasseur; Mohammad Samadi; John J. Mackrill; Hélène Greige-Gerges; Lizette Auezova; Gérard Lizard. 2020. "Prevention by Dietary Polyphenols (Resveratrol, Quercetin, Apigenin) Against 7-Ketocholesterol-Induced Oxiapoptophagy in Neuronal N2a Cells: Potential Interest for the Treatment of Neurodegenerative and Age-Related Diseases." Cells 9, no. 11: 2346.
The brain, which is a cholesterol-rich organ, can be subject to oxidative stress in a variety of pathophysiological conditions, age-related diseases and some rare pathologies. This can lead to the formation of 7-ketocholesterol (7KC), a toxic derivative of cholesterol mainly produced by auto-oxidation. So, preventing the neuronal toxicity of 7KC is an important issue to avoid brain damage. As there are numerous data in favor of the prevention of neurodegeneration by the Mediterranean diet, this study aimed to evaluate the potential of a series of polyphenols (resveratrol, RSV; quercetin, QCT; and apigenin, API) as well as ω3 and ω9 unsaturated fatty acids (α-linolenic acid, ALA; eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA, and oleic acid, OA) widely present in this diet, to prevent 7KC (50 µM)-induced dysfunction of N2a neuronal cells. When polyphenols and fatty acids were used at non-toxic concentrations (polyphenols: ≤6.25 µM; fatty acids: ≤25 µM) as defined by the fluorescein diacetate assay, they greatly reduce 7KC-induced toxicity. The cytoprotective effects observed with polyphenols and fatty acids were comparable to those of α-tocopherol (400 µM) used as a reference. These polyphenols and fatty acids attenuate the overproduction of reactive oxygen species and the 7KC-induced drop in mitochondrial transmembrane potential (ΔΨm) measured by flow cytometry after dihydroethidium and DiOC6(3) staining, respectively. Moreover, the studied polyphenols and fatty acids reduced plasma membrane permeability considered as a criterion for cell death measured by flow cytometry after propidium iodide staining. Our data show that polyphenols (RSV, QCT and API) as well as ω3 and ω9 unsaturated fatty acids (ALA, EPA, DHA and OA) are potent cytoprotective agents against 7KC-induced neurotoxicity in N2a cells. Their cytoprotective effects could partly explain the benefits of the Mediterranean diet on human health, particularly in the prevention of neurodegenerative diseases.
Aline Yammine; Thomas Nury; Anne Vejux; Norbert Latruffe; Dominique Vervandier-Fasseur; Mohammad Samadi; Hélène Greige-Gerges; Lizette Auezova; Gérard Lizard. Prevention of 7-Ketocholesterol-Induced Overproduction of Reactive Oxygen Species, Mitochondrial Dysfunction and Cell Death with Major Nutrients (Polyphenols, ω3 and ω9 Unsaturated Fatty Acids) of the Mediterranean Diet on N2a Neuronal Cells. Molecules 2020, 25, 2296 .
AMA StyleAline Yammine, Thomas Nury, Anne Vejux, Norbert Latruffe, Dominique Vervandier-Fasseur, Mohammad Samadi, Hélène Greige-Gerges, Lizette Auezova, Gérard Lizard. Prevention of 7-Ketocholesterol-Induced Overproduction of Reactive Oxygen Species, Mitochondrial Dysfunction and Cell Death with Major Nutrients (Polyphenols, ω3 and ω9 Unsaturated Fatty Acids) of the Mediterranean Diet on N2a Neuronal Cells. Molecules. 2020; 25 (10):2296.
Chicago/Turabian StyleAline Yammine; Thomas Nury; Anne Vejux; Norbert Latruffe; Dominique Vervandier-Fasseur; Mohammad Samadi; Hélène Greige-Gerges; Lizette Auezova; Gérard Lizard. 2020. "Prevention of 7-Ketocholesterol-Induced Overproduction of Reactive Oxygen Species, Mitochondrial Dysfunction and Cell Death with Major Nutrients (Polyphenols, ω3 and ω9 Unsaturated Fatty Acids) of the Mediterranean Diet on N2a Neuronal Cells." Molecules 25, no. 10: 2296.
Neurodegenerative diseases, particularly Parkinson’s and Alzheimer’s, have common features: protein accumulation, cell death with mitochondrial involvement and oxidative stress. Patients are treated to cure the symptoms, but the treatments do not target the causes; so, the disease is not stopped. It is interesting to look at the side of nutrition which could help prevent the first signs of the disease or slow its progression in addition to existing therapeutic strategies. Lipids, whether in the form of vegetable or animal oils or in the form of fatty acids, could be incorporated into diets with the aim of preventing neurodegenerative diseases. These different lipids can inhibit the cytotoxicity induced during the pathology, whether at the level of mitochondria, oxidative stress or apoptosis and inflammation. The conclusions of the various studies cited are oriented towards the preventive use of oils or fatty acids. The future of these lipids that can be used in therapy/prevention will undoubtedly involve a better delivery to the body and to the brain by utilizing lipid encapsulation.
Thomas Nury; Gérard Lizard; Anne Vejux. Lipids Nutrients in Parkinson and Alzheimer’s Diseases: Cell Death and Cytoprotection. International Journal of Molecular Sciences 2020, 21, 2501 .
AMA StyleThomas Nury, Gérard Lizard, Anne Vejux. Lipids Nutrients in Parkinson and Alzheimer’s Diseases: Cell Death and Cytoprotection. International Journal of Molecular Sciences. 2020; 21 (7):2501.
Chicago/Turabian StyleThomas Nury; Gérard Lizard; Anne Vejux. 2020. "Lipids Nutrients in Parkinson and Alzheimer’s Diseases: Cell Death and Cytoprotection." International Journal of Molecular Sciences 21, no. 7: 2501.
In the case of neurodegenerative pathologies, the therapeutic arsenal available is often directed towards the consequences of the disease. The purpose of this study is, therefore, to evaluate the ability of docosahexaenoic acid (DHA), a molecule present in certain foods and considered to have health benefits, to inhibit the cytotoxic effects of very long-chain fatty acids (C24:0, C26:0), which can contribute to the development of some neurodegenerative diseases. The effect of DHA (50 µM) on very long-chain fatty acid-induced toxicity was studied by several complementary methods: phase contrast microscopy to evaluate cell viability and morphology, the MTT test to monitor the impact on mitochondrial function, propidium iodide staining to study plasma membrane integrity, and DHE staining to measure oxidative stress. A Western blot assay was used to assess autophagy through modification of LC3 protein. The various experiments were carried out on the cellular model of 158N murine oligodendrocytes. In 158N cells, our data establish that DHA is able to inhibit all tested cytotoxic effects induced by very long-chain fatty acids.
Thomas Nury; Margaux Doria; Gérard Lizard; Anne Vejux. Docosahexaenoic Acid Attenuates Mitochondrial Alterations and Oxidative Stress Leading to Cell Death Induced by Very Long-Chain Fatty Acids in a Mouse Oligodendrocyte Model. International Journal of Molecular Sciences 2020, 21, 641 .
AMA StyleThomas Nury, Margaux Doria, Gérard Lizard, Anne Vejux. Docosahexaenoic Acid Attenuates Mitochondrial Alterations and Oxidative Stress Leading to Cell Death Induced by Very Long-Chain Fatty Acids in a Mouse Oligodendrocyte Model. International Journal of Molecular Sciences. 2020; 21 (2):641.
Chicago/Turabian StyleThomas Nury; Margaux Doria; Gérard Lizard; Anne Vejux. 2020. "Docosahexaenoic Acid Attenuates Mitochondrial Alterations and Oxidative Stress Leading to Cell Death Induced by Very Long-Chain Fatty Acids in a Mouse Oligodendrocyte Model." International Journal of Molecular Sciences 21, no. 2: 641.
Neurodegenerative diseases are characterized by oxidative stress, mitochondrial damage, and death of neuronal cells. To counteract such damage and to favor neurogenesis, neurotrophic factors could be used as therapeutic agents. Octadecaneuropeptide (ODN), produced by astrocytes, is a potent neuroprotective agent. In N2a cells, we studied the ability of ODN to promote neuronal differentiation. This parameter was evaluated by phase contrast microscopy, staining with crystal violet, cresyl blue, and Sulforhodamine 101. The effect of ODN on cell viability and mitochondrial activity was determined with fluorescein diacetate and DiOC6(3), respectively. The impact of ODN on the topography of mitochondria and peroxisomes, two tightly connected organelles involved in nerve cell functions and lipid metabolism, was evaluated by transmission electron microscopy and fluorescence microscopy: detection of mitochondria with MitoTracker Red, and peroxisome with an antibody directed against the ABCD3 peroxisomal transporter. The profiles in fatty acids, cholesterol, and cholesterol precursors were determined by gas chromatography, in some cases coupled with mass spectrometry. Treatment of N2a cells with ODN (10−14 M, 48 h) induces neurite outgrowth. ODN-induced neuronal differentiation was associated with modification of topographical distribution of mitochondria and peroxisomes throughout the neurites and did not affect cell viability and mitochondrial activity. The inhibition of ODN-induced N2a differentiation with H89, U73122, chelerythrine and U0126 supports the activation of a PKA/PLC/PKC/MEK/ERK-dependent signaling pathway. Although there is no difference in fatty acid profile between control and ODN-treated cells, the level of cholesterol and some of its precursors (lanosterol, desmosterol, lathosterol) was increased in ODN-treated cells. The ability of ODN to induce neuronal differentiation without cytotoxicity reinforces the interest for this neuropeptide with neurotrophic properties to overcome nerve cell damage in major neurodegenerative diseases.
Amira Namsi; Thomas Nury; Amira. S. Khan; Jérôme Leprince; David Vaudry; Claudio Caccia; Valerio Leoni; Atanas G. Atanasov; Marie-Christine Tonon; Olfa Masmoudi-Kouki; Gérard Lizard; Nury; Khan; Masmoudi- Kouki. Octadecaneuropeptide (ODN) Induces N2a Cells Differentiation through a PKA/PLC/PKC/MEK/ERK-Dependent Pathway: Incidence on Peroxisome, Mitochondria, and Lipid Profiles. Molecules 2019, 24, 3310 .
AMA StyleAmira Namsi, Thomas Nury, Amira. S. Khan, Jérôme Leprince, David Vaudry, Claudio Caccia, Valerio Leoni, Atanas G. Atanasov, Marie-Christine Tonon, Olfa Masmoudi-Kouki, Gérard Lizard, Nury, Khan, Masmoudi- Kouki. Octadecaneuropeptide (ODN) Induces N2a Cells Differentiation through a PKA/PLC/PKC/MEK/ERK-Dependent Pathway: Incidence on Peroxisome, Mitochondria, and Lipid Profiles. Molecules. 2019; 24 (18):3310.
Chicago/Turabian StyleAmira Namsi; Thomas Nury; Amira. S. Khan; Jérôme Leprince; David Vaudry; Claudio Caccia; Valerio Leoni; Atanas G. Atanasov; Marie-Christine Tonon; Olfa Masmoudi-Kouki; Gérard Lizard; Nury; Khan; Masmoudi- Kouki. 2019. "Octadecaneuropeptide (ODN) Induces N2a Cells Differentiation through a PKA/PLC/PKC/MEK/ERK-Dependent Pathway: Incidence on Peroxisome, Mitochondria, and Lipid Profiles." Molecules 24, no. 18: 3310.
In this work, new nanohybrids based on superparamagnetic iron oxide nanoparticles (SPIONs) were elaborated and discussed for the first time as nanovectors of a derivative molecule of trans-resveratrol (RSV), a natural antioxidant molecule, which can be useful for brain disease treatment. The derivative molecule was chemically synthesized (4’-hydroxy-4-(3-aminopropoxy) trans-stilbene: HAPtS) and then grafted onto SPIONs surface using an organosilane coupling agent, which is 3-chloropropyltriethoxysilane (CPTES) and based on nucleophilic substitution reactions. The amount of HAPtS loaded onto SPIONs surface was estimated by thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS) analyses at 116 µmol·g−1 SPIONs. The synthesized HAPtS molecule, as well as the associated nanohybrids, were fully characterized by transmission electron microscopy (TEM), XPS, TGA, infrared (IR) and UV-visible spectroscopies, dynamic light scattering (DLS), and zeta potential measurements. The in vitro biological assessment of the synthesized nanohybrid’s efficiency was carried out on C6 glioma cells and showed that the nanovector SPIONs-CPTES-HAPtS do not affect the mitochondrial metabolism (MTT test), but damage the plasma membrane (FDA test), which could contribute to limiting the proliferation of cancerous cells (clonogenic test) at a HAPtS concentration of 50 µM. These nanoparticles have a potential cytotoxic effect that could be used to eliminate cancer cells.
Fadoua Sallem; Rihab Haji; Dominique Vervandier-Fasseur; Thomas Nury; Lionel Maurizi; Julien Boudon; Gérard Lizard; Nadine Millot. Elaboration of Trans-Resveratrol Derivative-Loaded Superparamagnetic Iron Oxide Nanoparticles for Glioma Treatment. Nanomaterials 2019, 9, 287 .
AMA StyleFadoua Sallem, Rihab Haji, Dominique Vervandier-Fasseur, Thomas Nury, Lionel Maurizi, Julien Boudon, Gérard Lizard, Nadine Millot. Elaboration of Trans-Resveratrol Derivative-Loaded Superparamagnetic Iron Oxide Nanoparticles for Glioma Treatment. Nanomaterials. 2019; 9 (2):287.
Chicago/Turabian StyleFadoua Sallem; Rihab Haji; Dominique Vervandier-Fasseur; Thomas Nury; Lionel Maurizi; Julien Boudon; Gérard Lizard; Nadine Millot. 2019. "Elaboration of Trans-Resveratrol Derivative-Loaded Superparamagnetic Iron Oxide Nanoparticles for Glioma Treatment." Nanomaterials 9, no. 2: 287.
Polydopamine (pDA)-modified iron oxide core-shell nanoparticles (IONPs) are developed and designed as nanovectors of drugs. Reactive quinone of pDA enhances the binding efficiency of various biomolecules for targeted delivery. Glutathione disulfide (GSSG), an abundant thiol species in the cytoplasm, was immobilized on the pDA-IONP surface. It serves as a cellular trigger to release the drug from the nanoparticles providing an efficient platform for the drug delivery system. Additionally, GSSG on the surface was further modified to form S-nitrosoglutathione that can act as nitric oxide (NO) donors. These NPs were fully characterized using a transmission electronic microscopy (TEM), thermogravimetric analysis (TGA), dynamic light scattering (DLS), zeta potential, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR) and UV-vis spectroscopies. Doxorubicin (DOX) and docetaxel (DTX) are two anticancer drugs, which were loaded onto nanoparticles with respective loading efficiencies of 243 and 223 µmol/g of IONPs, calculated using TGA measurements. DOX release study, using UV-vis spectroscopy, showed a pH responsive behavior, making the elaborated nanocarrier a potential drug delivery system. (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) -2H-tetrazolium (MTS) and apoptosis assays were performed on PC3 cell lines to evaluate the efficiency of the developed nanocarriers. These nanoparticles thus can prove their worth in cancer treatment on account of their easy access to the site and release of drug in response to changes to internal parameters such as pH, chemicals, etc.
Nimisha Singh; Fadoua Sallem; Celine Mirjolet; Thomas Nury; Suban Kumar Sahoo; Nadine Millot; Rajender Kumar. Polydopamine Modified Superparamagnetic Iron Oxide Nanoparticles as Multifunctional Nanocarrier for Targeted Prostate Cancer Treatment. Nanomaterials 2019, 9, 138 .
AMA StyleNimisha Singh, Fadoua Sallem, Celine Mirjolet, Thomas Nury, Suban Kumar Sahoo, Nadine Millot, Rajender Kumar. Polydopamine Modified Superparamagnetic Iron Oxide Nanoparticles as Multifunctional Nanocarrier for Targeted Prostate Cancer Treatment. Nanomaterials. 2019; 9 (2):138.
Chicago/Turabian StyleNimisha Singh; Fadoua Sallem; Celine Mirjolet; Thomas Nury; Suban Kumar Sahoo; Nadine Millot; Rajender Kumar. 2019. "Polydopamine Modified Superparamagnetic Iron Oxide Nanoparticles as Multifunctional Nanocarrier for Targeted Prostate Cancer Treatment." Nanomaterials 9, no. 2: 138.
The present study consisted in evaluating the antioxidant, anti-inflammatory and cytoprotective properties of ethanolic extracts from three mint species (Mentha spicata L. (MS), Mentha pulegium L. (MP) and Mentha rotundifolia (L.) Huds (MR)) with biochemical methods on murine RAW 264.7 macrophages (a transformed macrophage cell line isolated from ascites of BALB/c mice infected by the Abelson leukemia virus). The total phenolic, flavonoid and carotenoid contents were determined with spectrophotometric methods. The antioxidant activities were quantified with the Kit Radicaux Libres (KRLTM), the ferric reducing antioxidant power (FRAP) and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. The MS extract showed the highest total phenolic content, and the highest antioxidant capacity, while the MR extract showed the lowest total phenolic content and the lowest antioxidant capacity. The cytoprotective and anti-inflammatory activities of the extracts were quantified on murine RAW 264.7 macrophages treated with 7-ketocholesterol (7KC; 20 µg/mL: 50 µM) associated or not for 24 h and 48 h with ethanolic mint extracts used at different concentrations (25, 50, 100, 200 and 400 µg/mL). Under treatment with 7KC, an important inhibition of cell growth was revealed with the crystal violet test. This side effect was strongly attenuated in a dose dependent manner with the different ethanolic mint extracts, mainly at 48 h. The most important cytoprotective effect was observed with the MS extract. In addition, the effects of ethanolic mint extracts on cytokine secretion (Interleukin (IL)-6, IL-10, Monocyte Chemoattractant Protein (MCP)-1, Interferon (IFN)-ϒ, Tumor necrosis factor (TNF)-α) were determined at 24 h on lipopolysaccharide (LPS, 0.2 µg/mL)-, 7KC (20 µg/mL)- and (7KC + LPS)-treated RAW 264.7 cells. Complex effects of mint extracts were observed on cytokine secretion. However, comparatively to LPS-treated cells, all the extracts strongly reduce IL-6 secretion and two of them (MP and MR) also decrease MCP-1 and TNF-α secretion. However, no anti-inflammatory effects were observed on 7KC- and (7KC + LPS)-treated cells. Altogether, these data bring new evidences on the potential benefits (especially antioxidant and cytoprotective properties) of Algerian mint on human health.
Fatiha Brahmi; Thomas Nury; Meryam Debbabi; Samia Hadj-Ahmed; Amira Zarrouk; Michel Prost; Khodir Madani; Lila Boulekbache-Makhlouf; Gérard Lizard. Evaluation of Antioxidant, Anti-Inflammatory and Cytoprotective Properties of Ethanolic Mint Extracts from Algeria on 7-Ketocholesterol-Treated Murine RAW 264.7 Macrophages. Antioxidants 2018, 7, 184 .
AMA StyleFatiha Brahmi, Thomas Nury, Meryam Debbabi, Samia Hadj-Ahmed, Amira Zarrouk, Michel Prost, Khodir Madani, Lila Boulekbache-Makhlouf, Gérard Lizard. Evaluation of Antioxidant, Anti-Inflammatory and Cytoprotective Properties of Ethanolic Mint Extracts from Algeria on 7-Ketocholesterol-Treated Murine RAW 264.7 Macrophages. Antioxidants. 2018; 7 (12):184.
Chicago/Turabian StyleFatiha Brahmi; Thomas Nury; Meryam Debbabi; Samia Hadj-Ahmed; Amira Zarrouk; Michel Prost; Khodir Madani; Lila Boulekbache-Makhlouf; Gérard Lizard. 2018. "Evaluation of Antioxidant, Anti-Inflammatory and Cytoprotective Properties of Ethanolic Mint Extracts from Algeria on 7-Ketocholesterol-Treated Murine RAW 264.7 Macrophages." Antioxidants 7, no. 12: 184.
Cholesterol oxidation products, also named oxysterols, can be formed either by cholesterol auto-oxidation, enzymatically or both. Among these oxysterols, 7-ketocholesterol (7KC) is mainly formed during radical attacks that take place on the carbon 7 of cholesterol. As increased levels of 7KC have been found in the tissues, plasma and/or cerebrospinal fluid of patients with major diseases, especially age-related diseases (cardiovascular diseases, eye diseases, neurodegenerative diseases), some cancers, and chronic inflammatory diseases, it is suspected that 7KC, could contribute to their development. Since 7KC, provided by the diet or endogenously formed, is not or little efficiently metabolized, except in hepatic cells, its cellular accumulation can trigger numerous side effects including oxidative stress, inflammation and cell death. To counteract 7KC-induced side effects, it is necessary to characterize the metabolic pathways activated by this oxysterol to identify potential targets for cytoprotection and geroprotection. Currently, several natural compounds (tocopherols, fatty acids, polyphenols, etc) or mixtures of compounds (oils) used in traditional medicine are able to inhibit the deleterious effects of 7KC. The different molecules identified could be valued in different ways (functional foods, recombinant molecules, theranostic) to prevent or treat diseases associated with 7KC.
Fatiha Brahmi; Anne Vejux; Randa Sghaier; Amira Zarrouk; Thomas Nury; Wiem Meddeb; Leila Rezig; Amira Namsi; Khouloud Sassi; Aline Yammine; Iham Badreddine; Dominique Vervandier-Fasseur; Khodir Madani; Lila Boulekbache-Makhlouf; Boubker Nasser; Gérard Lizard. Prevention of 7-ketocholesterol-induced side effects by natural compounds. Critical Reviews in Food Science and Nutrition 2018, 59, 3179 -3198.
AMA StyleFatiha Brahmi, Anne Vejux, Randa Sghaier, Amira Zarrouk, Thomas Nury, Wiem Meddeb, Leila Rezig, Amira Namsi, Khouloud Sassi, Aline Yammine, Iham Badreddine, Dominique Vervandier-Fasseur, Khodir Madani, Lila Boulekbache-Makhlouf, Boubker Nasser, Gérard Lizard. Prevention of 7-ketocholesterol-induced side effects by natural compounds. Critical Reviews in Food Science and Nutrition. 2018; 59 (19):3179-3198.
Chicago/Turabian StyleFatiha Brahmi; Anne Vejux; Randa Sghaier; Amira Zarrouk; Thomas Nury; Wiem Meddeb; Leila Rezig; Amira Namsi; Khouloud Sassi; Aline Yammine; Iham Badreddine; Dominique Vervandier-Fasseur; Khodir Madani; Lila Boulekbache-Makhlouf; Boubker Nasser; Gérard Lizard. 2018. "Prevention of 7-ketocholesterol-induced side effects by natural compounds." Critical Reviews in Food Science and Nutrition 59, no. 19: 3179-3198.
The propagation of nerve impulses in myelinated nerve fibers depends on a number of factors involving the myelin and neural axons. In several neurodegenerative diseases, nerve impulses can be affected by the structural and biochemical characteristics of the myelin sheath and the activity of ion channels located in the nodes of Ranvier. Though it is generally accepted that lipid disorders are involved in the development of neurodegenerative diseases, little is known about their impact on nerve impulses. Cholesterol oxide derivatives (also called oxysterols), which are either formed enzymatically or as a result of cholesterol auto-oxidation or both, are often found in abnormal levels in the brain and body fluids of patients with neurodegenerative diseases. This leads to the question of whether these molecules, which can accumulate in the plasma membrane and influence its structure and functions (fluidity, membrane proteins activities, signaling pathways), can have an impact on nerve impulses. It is currently thought that the ability of oxysterols to modulate nerve impulses could be explained by their influence on the characteristics and production of myelin as well as the functionality of Na+ and K+ channels.
Maryem Bezine; Amira Namsi; Randa Sghaier; Rym Ben Khalifa; Haithem Hamdouni; Fatiha Brahmi; Iham Badreddine; Wafa Mihoubi; Thomas Nury; Anne Vejux; Amira Zarrouk; Jérôme de Sèze; Thibault Moreau; Boubker Nasser; Gérard Lizard. The effect of oxysterols on nerve impulses. Biochimie 2018, 153, 46 -51.
AMA StyleMaryem Bezine, Amira Namsi, Randa Sghaier, Rym Ben Khalifa, Haithem Hamdouni, Fatiha Brahmi, Iham Badreddine, Wafa Mihoubi, Thomas Nury, Anne Vejux, Amira Zarrouk, Jérôme de Sèze, Thibault Moreau, Boubker Nasser, Gérard Lizard. The effect of oxysterols on nerve impulses. Biochimie. 2018; 153 ():46-51.
Chicago/Turabian StyleMaryem Bezine; Amira Namsi; Randa Sghaier; Rym Ben Khalifa; Haithem Hamdouni; Fatiha Brahmi; Iham Badreddine; Wafa Mihoubi; Thomas Nury; Anne Vejux; Amira Zarrouk; Jérôme de Sèze; Thibault Moreau; Boubker Nasser; Gérard Lizard. 2018. "The effect of oxysterols on nerve impulses." Biochimie 153, no. : 46-51.
In the prevention of neurodegeneration associated with aging and neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease), neuronal differentiation is of interest. In this context, neurotrophic factors are a family of peptides capable of promoting the growth, survival, and/or differentiation of both developing and immature neurons. In contrast to these peptidyl compounds, polyphenols are not degraded in the intestinal tract and are able to cross the blood–brain barrier. Consequently, they could potentially be used as therapeutic agents in neurodegenerative pathologies associated with neuronal loss, thus requiring the stimulation of neurogenesis. We therefore studied the ability to induce neuronal differentiation of two major polyphenols present in the Mediterranean diet: resveratrol (RSV), a major compound found in grapes and red wine, and apigenin (API), present in parsley, rosemary, olive oil, and honey. The effects of these compounds (RSV and API: 6.25–50 µM) were studied on murine neuro-2a (N2a) cells after 48 h of treatment without or with 10% fetal bovine serum (FBS). Retinoic acid (RA: 6.25–50 µM) was used as positive control. Neuronal differentiation was morphologically evaluated through the presence of dendrites and axons. Cell growth was determined by cell counting and cell viability by staining with fluorescein diacetate (FDA). Neuronal differentiation was more efficient in the absence of serum than with 10% FBS or 10% delipidized FBS. At concentrations inducing neuronal differentiation, no or slight cytotoxicity was observed with RSV and API, whereas RA was cytotoxic. Without FBS, RSV and API, as well as RA, trigger the neuronal differentiation of N2a cells via signaling pathways simultaneously involving protein kinase A (PKA)/phospholipase C (PLC)/protein kinase C (PKC) and MEK/ERK. With 10% FBS, RSV and RA induce neuronal differentiation via PLC/PKC and PKA/PLC/PKC, respectively. With 10% FBS, PKA and PLC/PKC as well as MEK/ERK signaling pathways were not activated in API-induced neuronal differentiation. In addition, the differentiating effects of RSV and API were not inhibited by cyclo[DLeu5] OP, an antagonist of octadecaneuropeptide (ODN) which is a neurotrophic factor. Moreover, RSV and API do not stimulate the expression of the diazepam-binding inhibitor (DBI), the precursor of ODN. Thus, RSV and API are able to induce neuronal differentiation, ODN and its receptor are not involved in this process, and the activation of the (PLC/PKC) signaling pathway is required, except with apigenin in the presence of 10% FBS. These data show that RSV and API are able to induce neuronal differentiation and therefore mimic neurotrophin activity. Thus, RSV and API could be of interest in regenerative medicine to favor neurogenesis.
Amira Namsi; Thomas Nury; Haithem Hamdouni; Aline Yammine; Anne Vejux; Dominique Vervandier-Fasseur; Norbert Latruffe; Olfa Masmoudi-Kouki; Gérard Lizard. Induction of Neuronal Differentiation of Murine N2a Cells by Two Polyphenols Present in the Mediterranean Diet Mimicking Neurotrophins Activities: Resveratrol and Apigenin. Diseases 2018, 6, 67 .
AMA StyleAmira Namsi, Thomas Nury, Haithem Hamdouni, Aline Yammine, Anne Vejux, Dominique Vervandier-Fasseur, Norbert Latruffe, Olfa Masmoudi-Kouki, Gérard Lizard. Induction of Neuronal Differentiation of Murine N2a Cells by Two Polyphenols Present in the Mediterranean Diet Mimicking Neurotrophins Activities: Resveratrol and Apigenin. Diseases. 2018; 6 (3):67.
Chicago/Turabian StyleAmira Namsi; Thomas Nury; Haithem Hamdouni; Aline Yammine; Anne Vejux; Dominique Vervandier-Fasseur; Norbert Latruffe; Olfa Masmoudi-Kouki; Gérard Lizard. 2018. "Induction of Neuronal Differentiation of Murine N2a Cells by Two Polyphenols Present in the Mediterranean Diet Mimicking Neurotrophins Activities: Resveratrol and Apigenin." Diseases 6, no. 3: 67.
The Asteraceae family is economically very important, because many of these plants are grown mainly for their food value, such as lettuce (Lactuca), chicory (Cichorium), and sunflower (Heliantus aminus). One of the typical properties of this family, which includes milk thistle (Sylibum marianum), is the richness of the oil in various compounds (flavonoids, alkaloids, tocopherols, and unsaturated fatty acids). Currently, and for the coming decades, age-related diseases, including neurodegenerative diseases, are a major public health problem. Preventing their appearance or opposing their evolution is a major objective. In this context, the cytoprotective activities of milk thistle seed oil produced in Tunisia were studied on the 158N model using 7-ketocholesterol (7KC) and 24S-hydroxycholesterol (24S) as cytotoxic agents. 7KC and 24S were used because they can be increased in the brain and body fluids of patients with major age-related neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. In order to evaluate the cytoprotective properties of milk thistle seed oil, complementary techniques of microscopy, flow cytometry, and biochemistry were used. The chemical composition of milk thistle seed oil has also been determined by various chromatography techniques. Milk thistle seed oils from different area of Tunisia are rich in tocopherols and are strongly antioxidant according to various biochemical tests (KRL (Kit Radicaux Libres), FRAP (Ferric Reducing Antioxidant Power), and DPPH (2,2-diphenyl-1-picrylhydrazyl)). The main fatty acids are linoleic acid (C18:2 n-6) and oleic acid (C18:1 n-9). The main polyphenols identified are homovanillic acid, p-coumaric acid, quercetin, and apigenin, with a predominance of vanillic acid. On 158N cells, milk thistle seed oil attenuates the cytotoxicity of 7KC and 24S including: loss of cell adhesion, increased plasma membrane permeability, mitochondrial dysfunction, overproduction of reactive oxygen species, induction of apoptosis, and autophagy. The attenuation of the cytotoxicity of 7KC and 24S observed with the milk thistle seed oil is in the order of that observed with α-tocopherol used as a positive control. In the presence of nigella seed oil, considered potentially cytotoxic, no cytoprotective effects were observed. Given the chemical characteristics, antioxidant properties, and cytoprotective activities of milk thistle seed oil, our results highlight the potential benefit of this oil for human health.
Wiem Meddeb; Leila Rezig; Amira Zarrouk; Thomas Nury; Anne Vejux; Michel Prost; Lionel Bretillon; Mondher Mejri; Gérard Lizard. Cytoprotective Activities of Milk Thistle Seed Oil Used in Traditional Tunisian Medicine on 7-Ketocholesterol and 24S-Hydroxycholesterol-Induced Toxicity on 158N Murine Oligodendrocytes. Antioxidants 2018, 7, 95 .
AMA StyleWiem Meddeb, Leila Rezig, Amira Zarrouk, Thomas Nury, Anne Vejux, Michel Prost, Lionel Bretillon, Mondher Mejri, Gérard Lizard. Cytoprotective Activities of Milk Thistle Seed Oil Used in Traditional Tunisian Medicine on 7-Ketocholesterol and 24S-Hydroxycholesterol-Induced Toxicity on 158N Murine Oligodendrocytes. Antioxidants. 2018; 7 (7):95.
Chicago/Turabian StyleWiem Meddeb; Leila Rezig; Amira Zarrouk; Thomas Nury; Anne Vejux; Michel Prost; Lionel Bretillon; Mondher Mejri; Gérard Lizard. 2018. "Cytoprotective Activities of Milk Thistle Seed Oil Used in Traditional Tunisian Medicine on 7-Ketocholesterol and 24S-Hydroxycholesterol-Induced Toxicity on 158N Murine Oligodendrocytes." Antioxidants 7, no. 7: 95.
Little is known about K+ regulation playing major roles in the propagation of nerve impulses, as well as in apoptosis and inflammasome activation involved in neurodegeneration. As increased levels of 7-ketocholesterol (7KC), 24S-hydroxycholesterol (24S-OHC) and tetracosanoic acid (C24:0) have been observed in patients with neurodegenerative diseases, we studied the effect of 24 and/or 48 h of treatment with 7KC, 24S-OHC and C24:0 on Kv3.1b potassium channel level, intracellular K+ concentration, oxidative stress, mitochondrial dysfunction, and plasma membrane permeability in 158N oligodendrocytes and BV-2 microglial cells. In 158N cells, whereas increased level of Kv3.1b was only observed with 7KC and 24S-OHC but not with C24:0 at 24 h, an intracellular accumulation of K+ was always detected. In BV-2 cells treated with 7KC, 24S-OHC and C24:0, Kv3.1b level was only increased at 48 h; intracellular K+ accumulation was found at 24 h with 7KC, 24S-OHC and C24:0, and only with C24:0 at 48 h. Positive correlations between Kv3.1b level and intracellular K+ concentration were observed in 158N cells in the presence of 7KC and 24S-OHC, and in 7KC-treated BV-2 cells at 48 h. Positive correlations were also found between Kv3.1b or the intracellular K+ concentration, overproduction of reactive oxygen species, loss of transmembrane mitochondrial potential and increased plasma membrane permeability in 158N and BV-2 cells. Our data support that the lipid environment affects Kv3.1b channel expression and/or functionality, and that the subsequent rupture of K+ homeostasis is relied with oligodendrocytes and microglial cells damages.
Maryem Bezine; Sonia Maatoug; Rym Ben Khalifa; Meryam Debbabi; Amira Zarrouk; Yuqin Wang; William J. Griffiths; Thomas Nury; Mohammad Samadi; Anne Vejux; Jérôme De Seze; Thibault Moreau; Riadh Kharrat; Mohamed El Ayeb; Gérard Lizard. Modulation of Kv3.1b potassium channel level and intracellular potassium concentration in 158N murine oligodendrocytes and BV-2 murine microglial cells treated with 7-ketocholesterol, 24S-hydroxycholesterol or tetracosanoic acid (C24:0). Biochimie 2018, 153, 56 -69.
AMA StyleMaryem Bezine, Sonia Maatoug, Rym Ben Khalifa, Meryam Debbabi, Amira Zarrouk, Yuqin Wang, William J. Griffiths, Thomas Nury, Mohammad Samadi, Anne Vejux, Jérôme De Seze, Thibault Moreau, Riadh Kharrat, Mohamed El Ayeb, Gérard Lizard. Modulation of Kv3.1b potassium channel level and intracellular potassium concentration in 158N murine oligodendrocytes and BV-2 murine microglial cells treated with 7-ketocholesterol, 24S-hydroxycholesterol or tetracosanoic acid (C24:0). Biochimie. 2018; 153 ():56-69.
Chicago/Turabian StyleMaryem Bezine; Sonia Maatoug; Rym Ben Khalifa; Meryam Debbabi; Amira Zarrouk; Yuqin Wang; William J. Griffiths; Thomas Nury; Mohammad Samadi; Anne Vejux; Jérôme De Seze; Thibault Moreau; Riadh Kharrat; Mohamed El Ayeb; Gérard Lizard. 2018. "Modulation of Kv3.1b potassium channel level and intracellular potassium concentration in 158N murine oligodendrocytes and BV-2 murine microglial cells treated with 7-ketocholesterol, 24S-hydroxycholesterol or tetracosanoic acid (C24:0)." Biochimie 153, no. : 56-69.
Argan oil is widely used in Morocco in traditional medicine. Its ability to treat cardiovascular diseases is well-established. However, nothing is known about its effects on neurodegenerative diseases, which are often associated with increased oxidative stress leading to lipid peroxidation and the formation of 7-ketocholesterol (7KC) resulting from cholesterol auto-oxidation. As 7KC induces oxidative stress, inflammation and cell death, it is important to identify compounds able to impair its harmful effects. These compounds may be either natural or synthetic molecules or mixtures of molecules such as oils. In this context: (i) the lipid profiles of dietary argan oils from Berkane and Agadir (Morocco) in fatty acids, phytosterols, tocopherols and polyphenols were determined by different chromatographic techniques; and (ii) their anti-oxidant and cytoprotective effects in 158N murine oligodendrocytes cultured with 7KC (25–50 µM; 24 h) without and with argan oil (0.1% v/v) or α-tocopherol (400 µM, positive control) were evaluated with complementary techniques of cellular and molecular biology. Among the unsaturated fatty acids present in argan oils, oleate (C18:1 n-9) and linoleate (C18:1 n-6) were the most abundant; the highest quantities of saturated fatty acids were palmitate (C16:0) and stearate (C18:0). Several phytosterols were found, mainly schottenol and spinasterol (specific to argan oil), cycloartenol, β-amyrin and citrostadienol. α- and γ-tocopherols were also present. Tyrosol and protocatechic acid were the only polyphenols detected. Argan and extra virgin olive oils have many compounds in common, principally oleate and linoleate, and tocopherols. Kit Radicaux Libres (KRL) and ferric reducing antioxidant power (FRAP) tests showed that argan and extra virgin olive oils have anti-oxidant properties. Argan oils were able to attenuate the cytotoxic effects of 7KC on 158N cells: loss of cell adhesion, cell growth inhibition, increased plasma membrane permeability, mitochondrial, peroxisomal and lysosomal dysfunction, and the induction of oxiapoptophagy (OXIdation + APOPTOsis + autoPHAGY). Altogether, our data obtained in 158N oligodendrocytes provide evidence that argan oil is able to counteract the toxic effects of 7KC on nerve cells, thus suggesting that some of its compounds could prevent or mitigate neurodegenerative diseases to the extent that they are able to cross the blood-brain barrier.
Asmaa Badreddine; Amira Zarrouk; El Mostafa Karym; Meryam Debbabi; Thomas Nury; Wiem Meddeb; Randa Sghaier; Maryem Bezine; Anne Vejux; Lucy Martine; Stéphane Grégoire; Lionel Bretillon; Emmanuelle Prost-Camus; Philippe Durand; Michel Prost; Thibault Moreau; Mustapha Cherkaoui-Malki; Boubker Nasser; Gérard Lizard. Argan Oil-Mediated Attenuation of Organelle Dysfunction, Oxidative Stress and Cell Death Induced by 7-Ketocholesterol in Murine Oligodendrocytes 158N. International Journal of Molecular Sciences 2017, 18, 2220 .
AMA StyleAsmaa Badreddine, Amira Zarrouk, El Mostafa Karym, Meryam Debbabi, Thomas Nury, Wiem Meddeb, Randa Sghaier, Maryem Bezine, Anne Vejux, Lucy Martine, Stéphane Grégoire, Lionel Bretillon, Emmanuelle Prost-Camus, Philippe Durand, Michel Prost, Thibault Moreau, Mustapha Cherkaoui-Malki, Boubker Nasser, Gérard Lizard. Argan Oil-Mediated Attenuation of Organelle Dysfunction, Oxidative Stress and Cell Death Induced by 7-Ketocholesterol in Murine Oligodendrocytes 158N. International Journal of Molecular Sciences. 2017; 18 (10):2220.
Chicago/Turabian StyleAsmaa Badreddine; Amira Zarrouk; El Mostafa Karym; Meryam Debbabi; Thomas Nury; Wiem Meddeb; Randa Sghaier; Maryem Bezine; Anne Vejux; Lucy Martine; Stéphane Grégoire; Lionel Bretillon; Emmanuelle Prost-Camus; Philippe Durand; Michel Prost; Thibault Moreau; Mustapha Cherkaoui-Malki; Boubker Nasser; Gérard Lizard. 2017. "Argan Oil-Mediated Attenuation of Organelle Dysfunction, Oxidative Stress and Cell Death Induced by 7-Ketocholesterol in Murine Oligodendrocytes 158N." International Journal of Molecular Sciences 18, no. 10: 2220.
We report the first Barton radical decarboxylation of unprotected bile acids via in situ irradiation of their thiohydroxamic esters in the presence of citraconic anhydride and citracoimide, leading to the synthesis a series of steroidal maleic anhydrides and maleimides as novel hybrid bile acids. The cytotoxic activities were evaluated on C6 rat glioma cells.
Mohammad Samadi; Thomas Nury; Ali Khalafi-Nezhad; Gérard Lizard. Protecting group-free radical decarboxylation of bile acids: Synthesis of novel steroidal substituted maleic anhydrides and maleimides and evaluation of their cytotoxicity on C6 rat glioma cells. Steroids 2017, 125, 124 -130.
AMA StyleMohammad Samadi, Thomas Nury, Ali Khalafi-Nezhad, Gérard Lizard. Protecting group-free radical decarboxylation of bile acids: Synthesis of novel steroidal substituted maleic anhydrides and maleimides and evaluation of their cytotoxicity on C6 rat glioma cells. Steroids. 2017; 125 ():124-130.
Chicago/Turabian StyleMohammad Samadi; Thomas Nury; Ali Khalafi-Nezhad; Gérard Lizard. 2017. "Protecting group-free radical decarboxylation of bile acids: Synthesis of novel steroidal substituted maleic anhydrides and maleimides and evaluation of their cytotoxicity on C6 rat glioma cells." Steroids 125, no. : 124-130.
The aim of the study was to compare the effect of sodium arsenate (AsV) on two different cell types: 158N murine oligodendrocytes and HepG2 human hepatoma cells. Exposure of 158N cells to AsV (0.1–400 µM; 48 h) induced a biphasic cytoxic effect defined as hormesis. Thus, low concentrations of AsV stimulate cell proliferation, as shown by phase-contrast microscopy, cell counting with trypan blue, and crystal violet assay, whereas high concentrations induce cell death associated with a loss of cell adhesion. These side effects were confirmed by staining with propidium iodide and cell cycle analysis, characterized by the presence of a subG1 peak, a criterion of apoptosis. The effects of AsV on mitochondrial function, as determined by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay, the measurement of mitochondrial transmembrane potential with 3,3′-dihexyloxacarbocyanine iodide, and the rate of mitochondrial adenosine triphosphate confirm the impact of AsV on the mitochondria. In contrast to 158N cells, HepG2 cells were susceptible to all AsV concentrations as shown by microscopic observations, by counting with trypan blue. However, no alteration is noted in the cell membrane integrity, which indicated an apoptotic mode of cell death, and this side effect is confirmed by the cycle analysis, which revealed a subG1 peak. Of note, there was a loss of MTT, suggesting that AsV induces mitochondrial complex II dysfunction. Altogether, our data show that the cytotoxic characteristics of AsV depend on the cell type considered.
Wafa Kharroubi; Thomas Nury; Samia Haj Ahmed; Pierre Andreoletti; Rachid Sakly; Mohamed Hammami; Gérard Lizard. Induction by arsenate of cell-type-specific cytotoxic effects in nerve and hepatoma cells. Human & Experimental Toxicology 2017, 36, 1256 -1269.
AMA StyleWafa Kharroubi, Thomas Nury, Samia Haj Ahmed, Pierre Andreoletti, Rachid Sakly, Mohamed Hammami, Gérard Lizard. Induction by arsenate of cell-type-specific cytotoxic effects in nerve and hepatoma cells. Human & Experimental Toxicology. 2017; 36 (12):1256-1269.
Chicago/Turabian StyleWafa Kharroubi; Thomas Nury; Samia Haj Ahmed; Pierre Andreoletti; Rachid Sakly; Mohamed Hammami; Gérard Lizard. 2017. "Induction by arsenate of cell-type-specific cytotoxic effects in nerve and hepatoma cells." Human & Experimental Toxicology 36, no. 12: 1256-1269.
The treatment of microglial BV-2 cells with sodium arsenate (As(V): 0.1-400μmol/L - 48hr) induces a dose-dependent response. The neurotoxic effects of high concentrations of As(V) (100, 200 and 400μmol/L) are characterized by increased levels of mitochondrial complexes I, II, and IV followed by increased superoxide anion generation. Moreover, As(V) triggers an apoptotic mode of cell death, demonstrated by an apoptotic SubG1 peak, associated with an alteration of plasma membrane integrity. There is also a decrease in transmembrane mitochondrial potential and mitochondrial adenosine triphosphate ATP. It is therefore tempting to speculate that As(V) triggers mitochondrial dysfunction, which may lead to defective oxidative phosphorylation subsequently causing mitochondrial oxidative damage, which in turn induces an apoptotic mode of cell death.
Wafa Kharroubi; Samia Haj Ahmed; Thomas Nury; Pierre Andreoletti; Rachid Sakly; Mohamed Hammami; Gérard Lizard. Mitochondrial dysfunction, oxidative stress and apoptotic induction in microglial BV-2 cells treated with sodium arsenate. Journal of Environmental Sciences 2017, 51, 44 -51.
AMA StyleWafa Kharroubi, Samia Haj Ahmed, Thomas Nury, Pierre Andreoletti, Rachid Sakly, Mohamed Hammami, Gérard Lizard. Mitochondrial dysfunction, oxidative stress and apoptotic induction in microglial BV-2 cells treated with sodium arsenate. Journal of Environmental Sciences. 2017; 51 ():44-51.
Chicago/Turabian StyleWafa Kharroubi; Samia Haj Ahmed; Thomas Nury; Pierre Andreoletti; Rachid Sakly; Mohamed Hammami; Gérard Lizard. 2017. "Mitochondrial dysfunction, oxidative stress and apoptotic induction in microglial BV-2 cells treated with sodium arsenate." Journal of Environmental Sciences 51, no. : 44-51.
Lipid peroxidation products, such as 7-ketocholesterol (7KC), may be increased in the body fluids and tissues of patients with neurodegenerative diseases and trigger microglial dysfunction involved in neurodegeneration. It is therefore important to identify synthetic and natural molecules able to impair the toxic effects of 7KC. We determined the impact of 7KC on murine microglial BV-2 cells, especially its ability to trigger mitochondrial and peroxisomal dysfunction, and evaluated the protective effects of α- and γ-tocopherol, Trolox, and oleic acid (OA). Multiple complementary chemical assays, flow cytometric and biochemical methods were used to evaluate the antioxidant and cytoprotective properties of these molecules. According to various complementary assays to estimate antioxidant activity, only α-, and γ-tocopherol, and Trolox had antioxidant properties. However, only α-tocopherol, γ-tocopherol and OA were able to impair 7KC-induced loss of mitochondrial transmembrane potential, which is associated with increased permeability to propidium iodide, an indicator of cell death. In addition, α-and γ-tocopherol, and OA were able to prevent the decrease in Abcd3 protein levels, which allows the measurement of peroxisomal mass, and in mRNA levels of Abcd1 and Abcd2, which encode for two transporters involved in peroxisomal β-oxidation. Thus, 7KC-induced side effects are associated with mitochondrial and peroxisomal dysfunction which can be inversed by natural compounds, thus supporting the hypothesis that the composition of the diet can act on the function of organelles involved in neurodegenerative diseases.
Meryam Debbabi; Thomas Nury; Amira Zarrouk; Nadia Mekahli; Maryem Bezine; Randa Sghaier; Stéphane Grégoire; Lucy Martine; Philippe Durand; Emmanuelle Camus; Anne Vejux; Aymen Jabrane; Lionel Bretillon; Michel Prost; Thibault Moreau; Sofien Ben Ammou; Mohamed Hammami; Gérard Lizard. Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells. International Journal of Molecular Sciences 2016, 17, 1973 .
AMA StyleMeryam Debbabi, Thomas Nury, Amira Zarrouk, Nadia Mekahli, Maryem Bezine, Randa Sghaier, Stéphane Grégoire, Lucy Martine, Philippe Durand, Emmanuelle Camus, Anne Vejux, Aymen Jabrane, Lionel Bretillon, Michel Prost, Thibault Moreau, Sofien Ben Ammou, Mohamed Hammami, Gérard Lizard. Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells. International Journal of Molecular Sciences. 2016; 17 (12):1973.
Chicago/Turabian StyleMeryam Debbabi; Thomas Nury; Amira Zarrouk; Nadia Mekahli; Maryem Bezine; Randa Sghaier; Stéphane Grégoire; Lucy Martine; Philippe Durand; Emmanuelle Camus; Anne Vejux; Aymen Jabrane; Lionel Bretillon; Michel Prost; Thibault Moreau; Sofien Ben Ammou; Mohamed Hammami; Gérard Lizard. 2016. "Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells." International Journal of Molecular Sciences 17, no. 12: 1973.
Exposure of human neuronal SK-N-BE cells to sodium arsenate (AsV 0.1-400 μM; 48 h) induced a biphasic toxic effect evoking hormesis. Indeed, at low concentrations, AsV stimulates cell proliferation visualized by phase contrast microscopy, whereas at high concentrations, an induction of cell death associated with a loss of cell adhesion was observed. These side effects were confirmed with crystal violet test, cell cycle analysis, evaluation of the percentage of Ki67 positive cells, and staining with propidium iodide. The impact of AsV on mitochondrial functions, which was determined by the MTT assay, the measurement of mitochondrial transmembrane potential with DiOC6(3), and the rate of mitochondrial ATP, also support an hormesis process. In addition, in the presence of high concentrations of AsV, a significant decrease of the protein expression of OXPHOS complexes of the respiratory chain was observed by western blot supporting that AsV-induced cell death is associated with mitochondrial alterations. Therefore, there are some evidences of hormesis on AsV-treated SK-N-BE cells, and at high concentrations, the mitochondria are a target of toxicity induced by AsV.
Wafa Kharroubi; Samia Haj Ahmed; Thomas Nury; Pierre Andreoletti; Zohra Haouas; Amira Zarrouk; Rachid Sakly; Mohamed Hammami; Gérard Lizard. Evidence of hormesis on human neuronal SK-N-BE cells treated with sodium arsenate: impact at the mitochondrial level. Environmental Science and Pollution Research 2016, 23, 8441 -8452.
AMA StyleWafa Kharroubi, Samia Haj Ahmed, Thomas Nury, Pierre Andreoletti, Zohra Haouas, Amira Zarrouk, Rachid Sakly, Mohamed Hammami, Gérard Lizard. Evidence of hormesis on human neuronal SK-N-BE cells treated with sodium arsenate: impact at the mitochondrial level. Environmental Science and Pollution Research. 2016; 23 (9):8441-8452.
Chicago/Turabian StyleWafa Kharroubi; Samia Haj Ahmed; Thomas Nury; Pierre Andreoletti; Zohra Haouas; Amira Zarrouk; Rachid Sakly; Mohamed Hammami; Gérard Lizard. 2016. "Evidence of hormesis on human neuronal SK-N-BE cells treated with sodium arsenate: impact at the mitochondrial level." Environmental Science and Pollution Research 23, no. 9: 8441-8452.