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Dr. Anne VEJUX
Team Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism EA 7270, INSERM, University of Bourgogne Franche-Comté, Dijon, France

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0 Apoptosis
0 Autophagy
0 Inflammation
0 Oxidative Stress
0 Necrosis

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Apoptosis
Oxidative Stress
Inflammation
Autophagy
Therapeutic
Natural molecules
Necrosis
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Journal article
Published: 09 June 2021 in The Journal of Steroid Biochemistry and Molecular Biology
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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.

ACS Style

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 Style

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.

Chicago/Turabian Style

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. 2021. "7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19." The Journal of Steroid Biochemistry and Molecular Biology 212, no. : 105939.

Journal article
Published: 19 May 2021 in Nutrients
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The multidrug resistance phenotype is a global phenomenon and causes chemotherapy failure in various cancers, such as in uterine sarcomas that have a high mortality rate. To overcome this phenotype, there is growing research interest in developing new treatment strategies. In this study, we highlight the potential of two essential oils from the Apiaceae family, Pituranthos chloranthus (PC) and Teucrium ramosissimum Desf. (TR), to act as chemopreventive and chemosensitizing agents against two uterine sarcoma cell lines, MES-SA and P-gp-overexpressing MES-SA/Dx5 cells. We found that PC and TR were able to inhibit the cell viability of sensitive MES-SA and resistant MES-SA/Dx5 cells by a slight modulation of the cell cycle and its regulators, but also through a significant induction of apoptosis. The molecular mechanism involved both caspase pathways associated with an overproduction of reactive oxygen species (ROS) and mitochondrial membrane depolarization. Very interestingly, the combination of doxorubicin with PC or TR induced a synergism to increase cell death in resistant MES-SA/Dx5 cells and, subsequently, had the benefit of decreasing the resistance index to doxorubicin. These synergistic effects were reinforced by a decrease in P-gp expression and its P-gp adenosine triphosphatase (ATPase) activity, which subsequently led to intracellular doxorubicin accumulation in resistant sarcoma cells.

ACS Style

Aida Lahmar; Aline Mathey; Virginie Aires; Dorra Elgueder; Anne Vejux; Rihab Khlifi; Fairouz Sioud; Leila Chekir-Ghedira; Dominique Delmas. Essential Oils, Pituranthos chloranthus and Teucrium ramosissimum, Chemosensitize Resistant Human Uterine Sarcoma MES-SA/Dx5 Cells to Doxorubicin by Inducing Apoptosis and Targeting P-Glycoprotein. Nutrients 2021, 13, 1719 .

AMA Style

Aida Lahmar, Aline Mathey, Virginie Aires, Dorra Elgueder, Anne Vejux, Rihab Khlifi, Fairouz Sioud, Leila Chekir-Ghedira, Dominique Delmas. Essential Oils, Pituranthos chloranthus and Teucrium ramosissimum, Chemosensitize Resistant Human Uterine Sarcoma MES-SA/Dx5 Cells to Doxorubicin by Inducing Apoptosis and Targeting P-Glycoprotein. Nutrients. 2021; 13 (5):1719.

Chicago/Turabian Style

Aida Lahmar; Aline Mathey; Virginie Aires; Dorra Elgueder; Anne Vejux; Rihab Khlifi; Fairouz Sioud; Leila Chekir-Ghedira; Dominique Delmas. 2021. "Essential Oils, Pituranthos chloranthus and Teucrium ramosissimum, Chemosensitize Resistant Human Uterine Sarcoma MES-SA/Dx5 Cells to Doxorubicin by Inducing Apoptosis and Targeting P-Glycoprotein." Nutrients 13, no. 5: 1719.

Review article
Published: 24 March 2021 in Ageing Research Reviews
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Age-related diseases for which there are no effective treatments include cardiovascular diseases; neurodegenerative diseases such as Alzheimer's disease; eye disorders such as cataract and age-related macular degeneration; and, more recently, Severe Acute Respiratory Syndrome (SARS-CoV-2). These diseases are associated with plasma and/or tissue increases in cholesterol derivatives mainly formed by auto-oxidation: 7-ketocholesterol, also known as 7-oxo-cholesterol, and 7β-hydroxycholesterol. The formation of these oxysterols can be considered as a consequence of mitochondrial and peroxisomal dysfunction, leading to increased in oxidative stress, which is accentuated with age. 7-ketocholesterol and 7β-hydroxycholesterol cause a specific form of cytotoxic activity defined as oxiapoptophagy, including oxidative stress and induction of death by apoptosis associated with autophagic criteria. Oxiaptophagy is associated with organelle dysfunction and in particular with mitochondrial and peroxisomal alterations involved in the induction of cell death and in the rupture of redox balance. As the criteria characterizing 7-ketocholesterol- and 7β-hydroxycholesterol-induced cytotoxicity are often simultaneously observed in major age-related diseases (cardiovascular diseases, age-related macular degeneration, Alzheimer’s disease) the involvement of these oxysterols in the pathophysiology of the latter seems increasingly likely. It is therefore important to better understand the signalling pathways associated with the toxicity of 7-ketocholesterol and 7β-hydroxycholesterol in order to identify pharmacological targets, nutrients and synthetic molecules attenuating or inhibiting the cytotoxic activities of these oxysterols. Numerous natural cytoprotective compounds have been identified: vitamins, fatty acids, polyphenols, terpenes, vegetal pigments, antioxidants, mixtures of compounds (oils, plant extracts) and bacterial enzymes. However, few synthetic molecules are able to prevent 7-ketocholesterol- and/or 7β-hydroxycholesterol-induced cytotoxicity: dimethyl fumarate, monomethyl fumarate, the tyrosine kinase inhibitor AG126, memantine, simvastatine, Trolox, dimethylsufoxide, mangafodipir and mitochondrial permeability transition pore (MPTP) inhibitors. The effectiveness of these compounds, several of which are already in use in humans, makes it possible to consider using them for the treatment of certain age-related diseases associated with increased plasma and/or tissue levels of 7-ketocholesterol and/or 7β-hydroxycholesterol.

ACS Style

T. Nury; A. Yammine; I. Ghzaiel; K. Sassi; A. Zarrouk; F. Brahmi; M. Samadi; S. Rup-Jacques; D. Vervandier-Fasseur; J.P. Pais de Barros; V. Bergas; S. Ghosh; M. Majeed; A. Pande; A. Atanasov; S. Hammami; J. Mackrill; B. Nasser; P. Andreoletti; M. Cherkaoui-Malki; A. Vejux; G. Lizard. Attenuation of 7-ketocholesterol- and 7β-hydroxycholesterol-induced oxiapoptophagy by nutrients, synthetic molecules and oils: Potential for the prevention of age-related diseases. Ageing Research Reviews 2021, 68, 101324 .

AMA Style

T. Nury, A. Yammine, I. Ghzaiel, K. Sassi, A. Zarrouk, F. Brahmi, M. Samadi, S. Rup-Jacques, D. Vervandier-Fasseur, J.P. Pais de Barros, V. Bergas, S. Ghosh, M. Majeed, A. Pande, A. Atanasov, S. Hammami, J. Mackrill, B. Nasser, P. Andreoletti, M. Cherkaoui-Malki, A. Vejux, G. Lizard. Attenuation of 7-ketocholesterol- and 7β-hydroxycholesterol-induced oxiapoptophagy by nutrients, synthetic molecules and oils: Potential for the prevention of age-related diseases. Ageing Research Reviews. 2021; 68 ():101324.

Chicago/Turabian Style

T. Nury; A. Yammine; I. Ghzaiel; K. Sassi; A. Zarrouk; F. Brahmi; M. Samadi; S. Rup-Jacques; D. Vervandier-Fasseur; J.P. Pais de Barros; V. Bergas; S. Ghosh; M. Majeed; A. Pande; A. Atanasov; S. Hammami; J. Mackrill; B. Nasser; P. Andreoletti; M. Cherkaoui-Malki; A. Vejux; G. Lizard. 2021. "Attenuation of 7-ketocholesterol- and 7β-hydroxycholesterol-induced oxiapoptophagy by nutrients, synthetic molecules and oils: Potential for the prevention of age-related diseases." Ageing Research Reviews 68, no. : 101324.

Journal article
Published: 05 March 2021 in The Journal of Steroid Biochemistry and Molecular Biology
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Multiple sclerosis is an autoimmune disease that affects the central nervous system. Dysfunction of the immune system leads to lesions that cause motor, sensory, cognitive, visual and/or sphincter disturbances. In the long term, these disorders can progress towards an irreversible handicap. The diagnosis takes time because there are no specific criteria to diagnose multiple sclerosis. To realize the diagnosis, a combination of clinical, biological, and radiological arguments is therefore required. Hence, there is a need to identify multiple sclerosis biomarkers. Some biomarkers target immunity through the detection of oligoclonal bands, the measurement of the IgG index and cytokines. During the physiopathological process, the blood-brain barrier can be broken, and this event can be identified by measuring metalloproteinase activity and diffusion of gadolinium in the brain by magnetic resonance imaging. Markers of demyelination and of astrocyte and microglial activity may also be of interest as well as markers of neuronal damage and mitochondrial status. The measurement of different lipids in the plasma and cerebrospinal fluid can also provide suitable information. These different lipids include fatty acids, fatty acid peroxidation products, phospholipids as well as oxidized derivatives of cholesterol (oxysterols). Oxysterols could constitute new biomarkers providing information on the form of multiple sclerosis, the outcome of the disease and the answer to treatment.

ACS Style

Anne Vejux; Imen Ghzaiel; Thomas Nury; Vincent Schneider; Karine Charrière; Randa Sghaier; Amira Zarrouk; Valerio Leoni; Thibault Moreau; Gérard Lizard. Oxysterols and multiple sclerosis: Physiopathology, evolutive biomarkers and therapeutic strategy. The Journal of Steroid Biochemistry and Molecular Biology 2021, 210, 105870 .

AMA Style

Anne Vejux, Imen Ghzaiel, Thomas Nury, Vincent Schneider, Karine Charrière, Randa Sghaier, Amira Zarrouk, Valerio Leoni, Thibault Moreau, Gérard Lizard. Oxysterols and multiple sclerosis: Physiopathology, evolutive biomarkers and therapeutic strategy. The Journal of Steroid Biochemistry and Molecular Biology. 2021; 210 ():105870.

Chicago/Turabian Style

Anne Vejux; Imen Ghzaiel; Thomas Nury; Vincent Schneider; Karine Charrière; Randa Sghaier; Amira Zarrouk; Valerio Leoni; Thibault Moreau; Gérard Lizard. 2021. "Oxysterols and multiple sclerosis: Physiopathology, evolutive biomarkers and therapeutic strategy." The Journal of Steroid Biochemistry and Molecular Biology 210, no. : 105870.

Journal article
Published: 23 October 2020 in Cells
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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.

ACS Style

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 Style

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 (11):2346.

Chicago/Turabian Style

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. 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.

Review article themed issue
Published: 24 June 2020 in British Journal of Pharmacology
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Oxysterols are oxidized forms of cholesterol generated from cholesterol by auto‐oxidation, enzymatic processes, or both. Some of them (7‐ketocholesterol, 7β‐hydroxycholesterol and 24(S)‐hydroxycholesterol), when used at cytotoxic concentrations on different cell types from different species (mesenchymal bone marrow cells, monocytic cells and nerve cells), induce a type of cell death associated with OXIdative stress and several characteristics of APOPTOsis and autoPHAGY, defined as oxiapoptophagy. Oxidative stress is associated with overproduction of ROS, increased antioxidant enzyme activities, lipid peroxidation and protein carbonylation. Apoptosis is associated with activation of the mitochondrial pathway, opening of the mitochondrial permeability pore, loss of mitochondrial membrane potential, caspase‐3 activation, PARP degradation, nuclear condensation and/or fragmentation. Autophagy is characterized by autophagic vacuoles revealed by monodansylcadaverine staining and transmission electron microscopy, plus increased ratio of LC‐3II/LC‐3I. In addition, morphological, topographical and functional changes of the peroxisome are observed.

ACS Style

Thomas Nury; Amira Zarrouk; Aline Yammine; John J. Mackrill; Anne Vejux; Gérard Lizard. Oxiapoptophagy: A type of cell death induced by some oxysterols. British Journal of Pharmacology 2020, 178, 3115 -3123.

AMA Style

Thomas Nury, Amira Zarrouk, Aline Yammine, John J. Mackrill, Anne Vejux, Gérard Lizard. Oxiapoptophagy: A type of cell death induced by some oxysterols. British Journal of Pharmacology. 2020; 178 (16):3115-3123.

Chicago/Turabian Style

Thomas Nury; Amira Zarrouk; Aline Yammine; John J. Mackrill; Anne Vejux; Gérard Lizard. 2020. "Oxiapoptophagy: A type of cell death induced by some oxysterols." British Journal of Pharmacology 178, no. 16: 3115-3123.

Journal article
Published: 13 May 2020 in Molecules
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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.

ACS Style

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 Style

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 (10):2296.

Chicago/Turabian Style

Aline 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.

Review
Published: 25 April 2020 in Molecules
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Silymarin extracted from milk thistle consisting of flavonolignan silybin has shown chemopreventive and chemosensitizing activity against various cancers. The present review summarizes the current knowledge on the potential targets of silymarin against various cancers. Silymarin may play on the system of xenobiotics, metabolizing enzymes (phase I and phase II) to protect normal cells against various toxic molecules or to protect against deleterious effects of chemotherapeutic agents on normal cells. Furthermore, silymarin and its main bioactive compounds inhibit organic anion transporters (OAT) and ATP-binding cassettes (ABC) transporters, thus contributing to counteracting potential chemoresistance. Silymarin and its derivatives play a double role, namely, limiting the progression of cancer cells through different phases of the cycle—thus forcing them to evolve towards a process of cell death—and accumulating cancer cells in a phase of the cell cycle—thus making it possible to target a greater number of tumor cells with a specific anticancer agent. Silymarin exerts a chemopreventive effect by inducing intrinsic and extrinsic pathways and reactivating cell death pathways by modulation of the ratio of proapoptotic/antiapoptotic proteins and synergizing with agonists of death domains receptors. In summary, we highlight how silymarin may act as a chemopreventive agent and a chemosensitizer through multiple pathways.

ACS Style

Dominique Delmas; Jianbo Xiao; Anne Vejux; Virginie Aires. Silymarin and Cancer: A Dual Strategy in Both in Chemoprevention and Chemosensitivity. Molecules 2020, 25, 2009 .

AMA Style

Dominique Delmas, Jianbo Xiao, Anne Vejux, Virginie Aires. Silymarin and Cancer: A Dual Strategy in Both in Chemoprevention and Chemosensitivity. Molecules. 2020; 25 (9):2009.

Chicago/Turabian Style

Dominique Delmas; Jianbo Xiao; Anne Vejux; Virginie Aires. 2020. "Silymarin and Cancer: A Dual Strategy in Both in Chemoprevention and Chemosensitivity." Molecules 25, no. 9: 2009.

Review
Published: 03 April 2020 in International Journal of Molecular Sciences
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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.

ACS Style

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 Style

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 (7):2501.

Chicago/Turabian Style

Thomas 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.

Journal article
Published: 18 January 2020 in International Journal of Molecular Sciences
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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.

ACS Style

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 Style

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 (2):641.

Chicago/Turabian Style

Thomas 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.

Review article
Published: 03 October 2019 in Biochemical Pharmacology
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Oxysterols are molecules derived by the oxidation of cholesterol and can be formed either by auto-oxidation, enzymatically or by both processes. Among the oxysterols formed by auto-oxidation, 7-ketocholesterol and 7β-hydroxycholesterol are the main forms generated. These oxysterols, formed endogenously and brought in large quantities by certain foods, have major cytotoxic properties. They are powerful inducers of oxidative stress, inducing dysfunction of organelles (mitochondria, lysosomes and peroxisomes) that can cause cell death. These molecules are often identified in increased amounts in common pathological states such as cardiovascular diseases, certain eye conditions, neurodegenerative disorders and inflammatory bowel diseases. To oppose the cytotoxic effects of these molecules, it is important to know their biological activities and the signaling pathways they affect. Numerous cell models of the vascular wall, eye, brain, and digestive tract have been used. Currently, to counter the cytotoxic effects of 7-ketocholesterol and 7β-hydroxycholesterol, natural molecules and oils, often associated with the Mediterranean diet, as well as synthetic molecules, have proved effective in vitro. Bioremediation approaches and the use of functionalized nanoparticles are also promising. At the moment, invertebrate and vertebrate models are mainly used to evaluate the metabolism and the toxicity of 7-ketocholesterol and 7β-hydroxycholesterol. The most frequently used models are mice, rats and rabbits. In order to cope with the difficulty of transferring the results obtained in animals to humans, the development of in vitro alternative methods such as organ/body-on-a-chip based on microfluidic technology are hopeful integrative approaches.

ACS Style

Anne Vejux; Dehbia Abed-Vieillard; Khadija Hajji; Amira Zarrouk; John J. Mackrill; Shubhrima Ghosh; Thomas Nury; Aline Yammine; Mohamed Zaibi; Wafa Mihoubi; Habiba Bouchab; Boubker Nasser; Yael Grosjean; Gérard Lizard. 7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity. Biochemical Pharmacology 2019, 173, 113648 .

AMA Style

Anne Vejux, Dehbia Abed-Vieillard, Khadija Hajji, Amira Zarrouk, John J. Mackrill, Shubhrima Ghosh, Thomas Nury, Aline Yammine, Mohamed Zaibi, Wafa Mihoubi, Habiba Bouchab, Boubker Nasser, Yael Grosjean, Gérard Lizard. 7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity. Biochemical Pharmacology. 2019; 173 ():113648.

Chicago/Turabian Style

Anne Vejux; Dehbia Abed-Vieillard; Khadija Hajji; Amira Zarrouk; John J. Mackrill; Shubhrima Ghosh; Thomas Nury; Aline Yammine; Mohamed Zaibi; Wafa Mihoubi; Habiba Bouchab; Boubker Nasser; Yael Grosjean; Gérard Lizard. 2019. "7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity." Biochemical Pharmacology 173, no. : 113648.

Review
Published: 08 August 2019 in International Journal of Molecular Sciences
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The immune response is essential to protect organisms from infection and an altered self. An organism’s overall metabolic status is now recognized as an important and long-overlooked mediator of immunity and has spurred new explorations of immune-related metabolic abnormalities. Peroxisomes are essential metabolic organelles with a central role in the synthesis and turnover of complex lipids and reactive species. Peroxisomes have recently been identified as pivotal regulators of immune functions and inflammation in the development and during infection, defining a new branch of immunometabolism. This review summarizes the current evidence that has helped to identify peroxisomes as central regulators of immunity and highlights the peroxisomal proteins and metabolites that have acquired relevance in human pathologies for their link to the development of inflammation, neuropathies, aging and cancer. This review then describes how peroxisomes govern immune signaling strategies such as phagocytosis and cytokine production and their relevance in fighting bacterial and viral infections. The mechanisms by which peroxisomes either control the activation of the immune response or trigger cellular metabolic changes that activate and resolve immune responses are also described.

ACS Style

Francesca Di Cara; Pierre Andreoletti; Doriane Trompier; Anne Vejux; Margret H. Bülow; Julia Sellin; Gérard Lizard; Mustapha Cherkaoui-Malki; Stéphane Savary. Peroxisomes in Immune Response and Inflammation. International Journal of Molecular Sciences 2019, 20, 3877 .

AMA Style

Francesca Di Cara, Pierre Andreoletti, Doriane Trompier, Anne Vejux, Margret H. Bülow, Julia Sellin, Gérard Lizard, Mustapha Cherkaoui-Malki, Stéphane Savary. Peroxisomes in Immune Response and Inflammation. International Journal of Molecular Sciences. 2019; 20 (16):3877.

Chicago/Turabian Style

Francesca Di Cara; Pierre Andreoletti; Doriane Trompier; Anne Vejux; Margret H. Bülow; Julia Sellin; Gérard Lizard; Mustapha Cherkaoui-Malki; Stéphane Savary. 2019. "Peroxisomes in Immune Response and Inflammation." International Journal of Molecular Sciences 20, no. 16: 3877.

Journal article
Published: 17 April 2019 in Free Radical Biology and Medicine
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In recent years, a particular interest has focused on the accumulation of fatty acids with very long chains (VLCFA) in the occurrence of neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis or dementia. Indeed, it seems increasingly clear that this accumulation of VLCFA in the central nervous system is accompanied by a progressive demyelination resulting in death of neuronal cells. Nevertheless, molecular mechanisms by which VLCFA result in toxicity remain unclear. This study highlights for the first time in 3 different cellular models (oligodendrocytes 158 N, primary mouse brain culture, and patient fibroblasts) the types of cell death involved where VLCFA-induced ROS production leads to autophagy. The autophagic process protects the cell from this VLCFA-induced toxicity. Thus, autophagy in addition to oxidative stress can offer new therapeutic approaches.

ACS Style

Margaux Doria; Thomas Nury; Dominique Delmas; Thibault Moreau; Gérard Lizard; Anne Vejux. Protective function of autophagy during VLCFA-induced cytotoxicity in a neurodegenerative cell model. Free Radical Biology and Medicine 2019, 137, 46 -58.

AMA Style

Margaux Doria, Thomas Nury, Dominique Delmas, Thibault Moreau, Gérard Lizard, Anne Vejux. Protective function of autophagy during VLCFA-induced cytotoxicity in a neurodegenerative cell model. Free Radical Biology and Medicine. 2019; 137 ():46-58.

Chicago/Turabian Style

Margaux Doria; Thomas Nury; Dominique Delmas; Thibault Moreau; Gérard Lizard; Anne Vejux. 2019. "Protective function of autophagy during VLCFA-induced cytotoxicity in a neurodegenerative cell model." Free Radical Biology and Medicine 137, no. : 46-58.

Book chapter
Published: 01 December 2018 in Resveratrol: State-of-the-Art Science and Health Applications
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There are compelling evidences that resveratrol act on immune systems by affecting the major type of immune cells and pro-inflammatory-cytokines associated lymphocytes. Resveratrol is able to interfere on the adaptative and innate immune responses trough a modulation of cytokine-associated immune cells, of the lymphocyte differentiation process and the ratio of the different subtypes of T lymphocytes. In this chapter, we discuss the resveratrol action on the different subtypes of immune cells and subsequently on the interleukin-associated production in various contexts of diseases (auto-immune diseases, cancers). We highlight in each case the molecular mechanism by which resveratrol modulates the immune and inflammatory response, in particular by modulating signaling pathways such as the NFκB pathway or MAPK pathways. By these immunomodulatory properties, resveratrol could provide a novel strategy to enhance the efficacy of immunotherapy in various human diseases.

ACS Style

Dominique Delmas; Emeric Limagne; Anne Vejux; François Ghiringhelli; Virginie Aires. A Link Between Immunity and Inflammation: Actionable Targets of Resveratrol. Resveratrol: State-of-the-Art Science and Health Applications 2018, 209 -237.

AMA Style

Dominique Delmas, Emeric Limagne, Anne Vejux, François Ghiringhelli, Virginie Aires. A Link Between Immunity and Inflammation: Actionable Targets of Resveratrol. Resveratrol: State-of-the-Art Science and Health Applications. 2018; ():209-237.

Chicago/Turabian Style

Dominique Delmas; Emeric Limagne; Anne Vejux; François Ghiringhelli; Virginie Aires. 2018. "A Link Between Immunity and Inflammation: Actionable Targets of Resveratrol." Resveratrol: State-of-the-Art Science and Health Applications , no. : 209-237.

Review
Published: 16 October 2018 in Critical Reviews in Food Science and Nutrition
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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.

ACS Style

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 Style

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 (19):3179-3198.

Chicago/Turabian Style

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. 2018. "Prevention of 7-ketocholesterol-induced side effects by natural compounds." Critical Reviews in Food Science and Nutrition 59, no. 19: 3179-3198.

Review
Published: 01 October 2018 in Biochimie
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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.

ACS Style

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 Style

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.

Chicago/Turabian Style

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. 2018. "The effect of oxysterols on nerve impulses." Biochimie 153, no. : 46-51.

Journal article
Published: 22 July 2018 in Diseases
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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.

ACS Style

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 Style

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 (3):67.

Chicago/Turabian Style

Amira 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.

Journal article
Published: 19 July 2018 in Antioxidants
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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.

ACS Style

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 Style

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 (7):95.

Chicago/Turabian Style

Wiem 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.

Journal article
Published: 17 February 2018 in Biochimie
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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.

ACS Style

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 Style

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.

Chicago/Turabian Style

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. 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.

Review article
Published: 31 January 2018 in Frontiers in Molecular Neuroscience
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Amyotrophic lateral sclerosis (ALS) is a non-demyelinating neurodegenerative disease in adults with motor disorders. Two forms exist: a sporadic form (90% of cases) and a family form due to mutations in more than 20 genes including the Superoxide dismutase 1, TAR DNA Binding Protein, Fused in Sarcoma, chromosome 9 open reading frame 72 and VAPB genes. The mechanisms associated with this pathology are beginning to be known: oxidative stress, glutamate excitotoxicity, protein aggregation, reticulum endoplasmic stress, neuroinflammation, alteration of RNA metabolism. In various neurodegenerative diseases, such as Alzheimer’s disease or multiple sclerosis, the involvement of lipids is increasingly suggested based on lipid metabolism modifications. With regard to ALS, research has also focused on the possible involvement of lipids. Lipid involvement was suggested for clinical arguments where changes in cholesterol and LDL/HDL levels were reported with, however, differences in positivity between studies. Since lipids are involved in the membrane structure and certain signaling pathways, it may be considered to look for oxysterols, mainly 25-hydroxycholesterol and its metabolites involved in immune response, or phytosterols to find suitable biomarkers for this pathology.

ACS Style

Anne Vejux; Amira Namsi; Thomas Nury; Thibault Moreau; Gérard Lizard. Biomarkers of Amyotrophic Lateral Sclerosis: Current Status and Interest of Oxysterols and Phytosterols. Frontiers in Molecular Neuroscience 2018, 11, 12 .

AMA Style

Anne Vejux, Amira Namsi, Thomas Nury, Thibault Moreau, Gérard Lizard. Biomarkers of Amyotrophic Lateral Sclerosis: Current Status and Interest of Oxysterols and Phytosterols. Frontiers in Molecular Neuroscience. 2018; 11 ():12.

Chicago/Turabian Style

Anne Vejux; Amira Namsi; Thomas Nury; Thibault Moreau; Gérard Lizard. 2018. "Biomarkers of Amyotrophic Lateral Sclerosis: Current Status and Interest of Oxysterols and Phytosterols." Frontiers in Molecular Neuroscience 11, no. : 12.