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Article ; Online: Oxiapoptophagy in Age-Related Diseases. Comment on Ouyang et al. 7-Ketocholesterol Induces Oxiapoptophagy and Inhibits Osteogenic Differentiation in MC3T3-E1 Cells.

Ghzaiel, Imen / Nury, Thomas / Zarrouk, Amira / Vejux, Anne / Lizard, Gérard

2022 Volume 11, Issue 22

Abstract: Due to the increase in life span and life expectancy, which can, however, be more or less pronounced depending on the economic, social and cultural context [ ... ]. ...

Abstract	Due to the increase in life span and life expectancy, which can, however, be more or less pronounced depending on the economic, social and cultural context [...].
MeSH term(s)	Osteogenesis ; Cell Differentiation ; Ketocholesterols ; Longevity
Chemical Substances	7-ketocholesterol (O7676FE78M) ; Ketocholesterols
Language	English
Publishing date	2022-11-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11223612
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Article ; Online: Cytoprotective effects of α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol on 7-ketocholesterol - Induced oxiapoptophagy: Major roles of PI3-K / PDK-1 / Akt signaling pathway and glutathione peroxidase activity in cell rescue.

Yammine, Aline / Ghzaiel, Imen / Pires, Vivien / Zarrouk, Amira / Kharoubi, Omar / Greige-Gerges, Hélène / Auezova, Lizette / Lizard, Gérard / Vejux, Anne

Current research in toxicology

2024 Volume 6, Page(s) 100153

Abstract: On murine N2a cells, 7-ketocholesterol induced an oxiapotophagic mode of cell death characterized by oxidative stress (reactive oxygen species overproduction on whole cells and at the mitochondrial level; lipid peroxidation), apoptosis induction (caspase- ...

Abstract	On murine N2a cells, 7-ketocholesterol induced an oxiapotophagic mode of cell death characterized by oxidative stress (reactive oxygen species overproduction on whole cells and at the mitochondrial level; lipid peroxidation), apoptosis induction (caspase-9, -3 and -7 cleavage, PARP degradation) and autophagy (increased ratio LC3-II / LC3-I). Oxidative stress was strongly attenuated by diphenyleneiodonium chloride which inhibits NAD(P)H oxidase. Mitochondrial and peroxisomal morphological and functional changes were also observed. Down regulation of PDK1 / Akt signaling pathways as well as of GSK3 / Mcl-1 and Nrf2 pathways were simultaneously observed in 7-ketocholesterol-induced oxiapoptophagy. These events were prevented by α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol. The inhibition of the cytoprotection by LY-294002, a PI3-K inhibitor, demonstrated an essential role of PI3-K in cell rescue. The rupture of oxidative stress in 7-ketocholesterol-induced oxiapoptophagy was also associated with important modifications of glutathione peroxidase, superoxide dismutase and catalase activities as well as of glutathione peroxidase-1, superoxide dismutase-1 and catalase level and expression. These events were also counteracted by α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol. The inhibition of the cytoprotection by mercaptosuccinic acid, a glutathione peroxidase inhibitor, showed an essential role of this enzyme in cell rescue. Altogether, our data support that the reactivation of PI3-K and glutathione peroxidase activities by α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol are essential to prevent 7KC-induced oxiapoptophagy.
Language	English
Publishing date	2024-02-08
Publishing country	Netherlands
Document type	Journal Article
ISSN	2666-027X
ISSN (online)	2666-027X
DOI	10.1016/j.crtox.2024.100153
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Article ; Online: Anti-glycation, antiplatelet and antioxidant effects of different pomegranate parts

Amri, Zahra / Amor, Ikram Ben / Zarrouk, Amira / Chaaba, Raja / Gargouri, Jalel / Hammami, Mohamed / Hammami, Sonia

BMC Complement Med Ther. 2022 Dec., v. 22, no. 1 p.339-339

2022

Abstract: BACKGROUND: Platelet aggregation and advanced glycation end products (AGEs) and oxidative stress are known as key factors for the development of cardiovascular diseases and diabetic complications. In this context, fruit and vegetable consumption, good ... ...

Abstract	BACKGROUND: Platelet aggregation and advanced glycation end products (AGEs) and oxidative stress are known as key factors for the development of cardiovascular diseases and diabetic complications. In this context, fruit and vegetable consumption, good sources of antioxidant compounds have been largely reported as an effective way of preventing human against these diseases. The current study focuses on the evaluation of antioxidant, antiplatelet and anti-glycation activities of pomegranate (Punica granatum L.) flowers (PF), leaves (PL), peel (PP) juice (PJ) and seeds oil (PSO). METHODS: Antioxidant activities was measured against ABTS radical and lipid peroxidation. Antiglycation activity was determined using the formation of AGE fluorescence intensity in the BSA/ribose system. Antiplatelet activity was measured in platelet rich plasma (PRP) against adenosine diphosphate (ADP), Collagen and arachidonic acid (AA). RESULTS: PF extract displayed the highest antioxidant activity against ABTS and lipid peroxidation with IC₅₀ values of 0.7 mg/mL and 0.63 mg/mL respectively. For anti-glycation activity, PP, PF and PL inhibited moderately the pentosidine-like AGEs formation compared to positive controls with AGE-IC₅₀ value of 0.4 mg/mL. PJ and PSO haven’t any anti-AGE effect. All the extracts selectively inhibited platelet aggregation caused by one, two or three inducers in dose dependent manner. PF was the most potent inhibitor caused by all three inducers, with inhibitory effects ranging from 35.6 to 66.6%. PP and PJ exhibited antiplatelet effect against both ADP and collagen and PL and PSO only against AA. CONCLUSIONS: These results suggest that some pomegranate extracts exert potential in vitro anti-glycative and antiplatelet activities.
Keywords	Punica granatum ; adenosine diphosphate ; antioxidant activity ; antioxidants ; arachidonic acid ; collagen ; complement ; dose response ; fluorescence ; fruits ; humans ; juices ; lipid peroxidation ; oils ; oxidative stress ; platelet aggregation ; pomegranates ; ribose ; vegetable consumption
Language	English
Dates of publication	2022-12
Size	p. 339.
Publishing place	BioMed Central
Document type	Article ; Online
ISSN	2662-7671
DOI	10.1186/s12906-022-03824-6
Database	NAL-Catalogue (AGRICOLA)

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Article: 7-Ketocholesterol- and 7β-Hydroxycholesterol-Induced Peroxisomal Disorders in Glial, Microglial and Neuronal Cells: Potential Role in Neurodegeneration : 7-ketocholesterol and 7β-hydroxycholesterol-Induced Peroxisomal Disorders and Neurodegeneration.

Nury, Thomas / Yammine, Aline / Menetrier, Franck / Zarrouk, Amira / Vejux, Anne / Lizard, Gérard

Advances in experimental medicine and biology

2021 Volume 1299, Page(s) 31–41

Abstract: Peroxisomopathies are qualitative or quantitative deficiencies in peroxisomes which lead to increases in the level of very-long-chain fatty acids (VLCFA) and can be associated with more or less pronounced dysfunction of central nervous system cells: ... ...

Abstract	Peroxisomopathies are qualitative or quantitative deficiencies in peroxisomes which lead to increases in the level of very-long-chain fatty acids (VLCFA) and can be associated with more or less pronounced dysfunction of central nervous system cells: glial and microglial cells. Currently, in frequent neurodegenerative diseases, Alzheimer's disease (AD) and multiple sclerosis (MS), peroxisomal dysfunction is also suspected due to an increase in VLCFA, which can be associated with a decrease of plasmalogens, in these patients. Moreover, in patients suffering from peroxisomopathies, such as X-linked adrenoleukodystrophy (X-ALD), AD, or MS, the increase in oxidative stress observed leads to the formation of cytotoxic oxysterols: 7-ketocholesterol (7KC) and 7β-hydroxycholesterol (7β-OHC). These observations led to the demonstration that 7KC and 7β-OHC alter the biogenesis and activity of peroxisomes in glial and microglial cells. In X-ALD, AD, and MS, it is suggested that 7KC and 7β-OHC affecting the peroxisome, and which also induce mitochondrial dysfunctions, oxidative stress, and inflammation, could promote neurodegeneration. Consequently, the study of oxisome in peroxisomopathies, AD and MS, could help to better understand the pathophysiology of these diseases to identify therapeutic targets for effective treatments.
MeSH term(s)	Humans ; Hydroxycholesterols/metabolism ; Ketocholesterols/metabolism ; Microglia/metabolism ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/pathology ; Neuroglia/metabolism ; Neurons/metabolism ; Peroxisomal Disorders/metabolism ; Peroxisomal Disorders/pathology
Chemical Substances	Hydroxycholesterols ; Ketocholesterols ; cholest-5-en-3 beta,7 alpha-diol (566-26-7) ; 7-ketocholesterol (O7676FE78M)
Language	English
Publishing date	2021-01-08
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-030-60204-8_3
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Article ; Online: Impact of Oxysterols on Cell Death, Proliferation, and Differentiation Induction: Current Status.

de Freitas, Fábio Alessandro / Levy, Débora / Zarrouk, Amira / Lizard, Gérard / Bydlowski, Sérgio Paulo

Cells

2021 Volume 10, Issue 9

Abstract: Oxysterols are oxidized derivatives of cholesterol produced by enzymatic activity or non-enzymatic pathways (auto-oxidation). The oxidation processes lead to the synthesis of about 60 different oxysterols. Several oxysterols have physiological, ... ...

Abstract	Oxysterols are oxidized derivatives of cholesterol produced by enzymatic activity or non-enzymatic pathways (auto-oxidation). The oxidation processes lead to the synthesis of about 60 different oxysterols. Several oxysterols have physiological, pathophysiological, and pharmacological activities. The effects of oxysterols on cell death processes, especially apoptosis, autophagy, necrosis, and oxiapoptophagy, as well as their action on cell proliferation, are reviewed here. These effects, also observed in several cancer cell lines, could potentially be useful in cancer treatment. The effects of oxysterols on cell differentiation are also described. Among them, the properties of stimulating the osteogenic differentiation of mesenchymal stem cells while inhibiting adipogenic differentiation may be useful in regenerative medicine.
MeSH term(s)	Animals ; Cell Death/drug effects ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Humans ; Oxidation-Reduction/drug effects ; Oxysterols/pharmacology
Chemical Substances	Oxysterols
Language	English
Publishing date	2021-09-03
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10092301
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Article ; Online: Cytoprotective activities of representative nutrients from the Mediterranean diet and of Mediterranean oils against 7-ketocholesterol- and 7β-hydroxycholesterol-induced cytotoxicity: Application to age-related diseases and civilization diseases.

Rezig, Leila / Ghzaiel, Imen / Ksila, Mohamed / Yammine, Aline / Nury, Thomas / Zarrouk, Amira / Samadi, Mohammad / Chouaibi, Moncef / Vejux, Anne / Lizard, Gérard

Steroids

2022 Volume 187, Page(s) 109093

Abstract: 7-ketocholesterol and 7β-hydroxycholesterol are two oxysterols mainly formed by the autoxidation of cholesterol. These two molecules are interconvertible via specific enzymes. These two oxysterols are often observed at increased amounts in biological ... ...

Abstract	7-ketocholesterol and 7β-hydroxycholesterol are two oxysterols mainly formed by the autoxidation of cholesterol. These two molecules are interconvertible via specific enzymes. These two oxysterols are often observed at increased amounts in biological fluids as well as tissues and organs affected during age-related diseases and in diseases of civilization such as cardiovascular, neurodegenerative, and ocular diseases as well as type 2 diabetes and metabolic syndrome. Noteworthy, 7-ketocholesterol and 7β-hydroxycholesterol induce oxidative stress and inflammation, which are frequently observed in patients with age-related and civilization diseases. For this reason, the involvement of these two oxysterols in the pathophysiology of these diseases is widely suspected. In addition, the toxicity of these oxysterols can lead to death by oxiapoptophagy characterized by oxidative stress, apoptosis induction and autophagy criteria. To prevent, or even treat, certain age-related or civilization diseases associated with increased levels of 7-ketocholesterol and 7β-hydroxycholesterol, the identification of molecules or mixtures of molecules attenuating or inhibiting the toxic effects of these oxysterols allows to consider new treatments. In this context, many nutrients present in significant amounts in the Mediterranean diet, especially tocopherols, fatty acids, and polyphenols, have shown cytoprotective activities as well as several Mediterranean oils (argan and olive oils, milk thistle seed oil, and pistacia lentiscus seed oil). Consequently, a nutraceutical approach, rich in nutrients present in the Mediterranean diet, could thus make it possible to counteract certain age-related and civilization diseases associated with increased levels of 7-ketocholesterol and 7β-hydroxycholesterol.
MeSH term(s)	Aging ; Civilization ; Diabetes Mellitus, Type 2 ; Diet, Mediterranean ; Fatty Acids ; Humans ; Hydroxycholesterols/pharmacology ; Ketocholesterols/pharmacology ; Nutrients ; Oils ; Olive Oil ; Polyphenols ; Tocopherols
Chemical Substances	Fatty Acids ; Hydroxycholesterols ; Ketocholesterols ; Oils ; Olive Oil ; Polyphenols ; cholest-5-en-3 beta,7 alpha-diol (566-26-7) ; 7-ketocholesterol (O7676FE78M) ; Tocopherols (R0ZB2556P8)
Language	English
Publishing date	2022-08-24
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80312-1
ISSN	1878-5867 ; 0039-128X
ISSN (online)	1878-5867
ISSN	0039-128X
DOI	10.1016/j.steroids.2022.109093
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Article ; Online: Role of Bioactive Compounds in the Regulation of Mitochondrial Dysfunctions in Brain and Age-Related Neurodegenerative Diseases.

Kessas, Khadidja / Chouari, Zhor / Ghzaiel, Imen / Zarrouk, Amira / Ksila, Mohamed / Ghrairi, Taoufik / El Midaoui, Adil / Lizard, Gérard / Kharoubi, Omar

Cells

2022 Volume 11, Issue 2

Abstract: Mitochondria are multifunctional organelles that participate in a wide range of metabolic processes, including energy production and biomolecule synthesis. The morphology and distribution of intracellular mitochondria change dynamically, reflecting a ... ...

Abstract	Mitochondria are multifunctional organelles that participate in a wide range of metabolic processes, including energy production and biomolecule synthesis. The morphology and distribution of intracellular mitochondria change dynamically, reflecting a cell's metabolic activity. Oxidative stress is defined as a mismatch between the body's ability to neutralise and eliminate reactive oxygen and nitrogen species (ROS and RNS). A determination of mitochondria failure in increasing oxidative stress, as well as its implications in neurodegenerative illnesses and apoptosis, is a significant developmental process of focus in this review. The neuroprotective effects of bioactive compounds linked to neuronal regulation, as well as related neuronal development abnormalities, will be investigated. In conclusion, the study of secondary components and the use of mitochondrial features in the analysis of various neurodevelopmental diseases has enabled the development of a new class of mitochondrial-targeted pharmaceuticals capable of alleviating neurodegenerative disease states and enabling longevity and healthy ageing for the vast majority of people.
MeSH term(s)	Aging/pathology ; Animals ; Brain/pathology ; Humans ; Mitochondria/drug effects ; Mitochondria/metabolism ; Mitochondria/pathology ; Neurodegenerative Diseases/pathology ; Neuroprotective Agents/chemistry ; Neuroprotective Agents/pharmacology ; Oxidative Stress/drug effects
Chemical Substances	Neuroprotective Agents
Language	English
Publishing date	2022-01-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11020257
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Article ; Online: DNA and neutral lipid contents of peripheral cells as predictive biomarkers of mild cognitive impairment and Alzheimer's disease: Highlights on the interest of a cytomic approach for the characterization of dementia.

Zarrouk, Amira / Lizard, Gérard

Cytometry. Part A : the journal of the International Society for Analytical Cytology

2015 Volume 87, Issue 1, Page(s) 3–4

MeSH term(s)	Alzheimer Disease/blood ; Alzheimer Disease/diagnosis ; Alzheimer Disease/pathology ; Azo Compounds ; Biomarkers/blood ; Cell Nucleus/chemistry ; Cell Nucleus/ultrastructure ; Cognitive Dysfunction/blood ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/pathology ; DNA/blood ; Flow Cytometry ; Fluorescent Dyes ; Humans ; Indoles ; Leukocytes, Mononuclear/chemistry ; Leukocytes, Mononuclear/ultrastructure ; Lipids/blood ; Mouth Mucosa/chemistry ; Mouth Mucosa/ultrastructure ; Organelle Shape
Chemical Substances	Azo Compounds ; Biomarkers ; Fluorescent Dyes ; Indoles ; Lipids ; DAPI (47165-04-8) ; DNA (9007-49-2) ; oil red O (G7S71FND9B)
Language	English
Publishing date	2015-01
Publishing country	United States
Document type	Letter
ZDB-ID	2099868-5
ISSN	1552-4930 ; 0196-4763 ; 1552-4922
ISSN (online)	1552-4930
ISSN	0196-4763 ; 1552-4922
DOI	10.1002/cyto.a.22572
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Article ; Online: Prevalence and factors associated with frailty in hospitalized older patients.

Hammami, Sonia / Zarrouk, Amira / Piron, Cecile / Almas, Ioana / Sakly, Nabil / Latteur, Veronique

BMC geriatrics

2020 Volume 20, Issue 1, Page(s) 144

Abstract: Background: Frailty is a multidimensional syndrome that leads to an increase of an age-related disorder of several physiological systems, and cognitive abilities decline. The aim of this study was to evaluate the prevalence of frailty among older ... ...

Abstract	Background: Frailty is a multidimensional syndrome that leads to an increase of an age-related disorder of several physiological systems, and cognitive abilities decline. The aim of this study was to evaluate the prevalence of frailty among older persons in Belgium and we examined the factors associated with frailty with a principal focus en cognitive, dietary status, and inflammatory parameters. Methods: A total of 124 participants (90 women, 34 men; age: mean ± SD: 85.9 ± 5.5 years) were studied, recruited from the Geriatrics department, Belgium. Nutritional, cognitive status and physical activity were assessed using Mini Mental State Examination score (MMSE), Mini Nutritional Assessment score (MNA), and Katz score, respectively. Frailty syndrome was evaluated using the modified Short Emergency Geriatric Assessment (SEGA) score. Medication and medical history were recorded. Analyzed biochemical parameters included C-reactive protein (CRP), complete blood count, blood creatinine, vitamin D level, and serum protein electrophoresis. According to SEGA score, participants were divided into non-frail (n = 19), frail (n = 25) and severely frail patients (n = 80). Results: The SEGA score was inversely correlated with MMSE, MNA and Katz score. SEGA. score was negatively correlated to albumin levels (r = - 0.30; p < 0.001) and positively correlated to CRP, polypharmacy and age (r = 0.28, r = 0.37, r = 0.33 and p < 0.01 respectively). Logistic regression showed a strong association between frailty, Katz score, dementia, polypharmacy and living in nursing home. Conclusion: Our results provide useful information for understanding mechanisms of frailty. This will help to develop preventive strategies for the elderly at the pre-frailty stage.
MeSH term(s)	Activities of Daily Living ; Aged ; Aged, 80 and over ; Belgium/epidemiology ; Cross-Sectional Studies ; Female ; Frail Elderly ; Frailty/diagnosis ; Frailty/epidemiology ; Geriatric Assessment/methods ; Humans ; Inpatients/statistics & numerical data ; Male ; Prevalence
Language	English
Publishing date	2020-04-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2059865-8
ISSN	1471-2318 ; 1471-2318
ISSN (online)	1471-2318
ISSN	1471-2318
DOI	10.1186/s12877-020-01545-4
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Article ; Online: Evaluation of pro-inflammatory cytokines in frail Tunisian older adults.

Hammami, Sonia / Ghzaiel, Imen / Hammouda, Souha / Sakly, Nabil / Hammami, Mohamed / Zarrouk, Amira

PloS one

2020 Volume 15, Issue 11, Page(s) e0242152

Abstract: The present study was undertaken to evaluate serum levels of pro-inflammatory cytokines in Tunisian older adults and to examine the relationships between inflammatory marker levels, geriatric, and biochemical parameters. A cross-sectional study was ... ...

Abstract	The present study was undertaken to evaluate serum levels of pro-inflammatory cytokines in Tunisian older adults and to examine the relationships between inflammatory marker levels, geriatric, and biochemical parameters. A cross-sectional study was conducted in a population of Tunisian older adults (N = 141, aged 65 and over). Patients were recruited from the Department of Internal Medicine, Fattouma Bourguiba University Hospital (Monastir, Tunisia) and from a nursing home (Sousse, Tunisia). Comprehensive geriatric assessment, history taking and examination including functional and nutritional assessment were done for each participant. Enzyme-linked immunosorbent assay (ELISA) test was used to measure serum cytokine (TNF-α, IL-8, IL-6) levels. The modified Short Emergency Geriatric Assessment score (SEGAm) were used to classify patients as 51 very-frail, 40 frail, and 50 non-frail. The age of the participants (80 men, 61 women) ranged from 65 to 97 years. Serum levels of TNF-α, IL-8 and C-reactive protein (CRP) were significantly higher in very-frail participants compared to frail and non-frail ones. However, no significant differences in IL-6 levels were detected among frailty groups. After adjustment for age, CRP and IL-8 levels remained significantly associated with frailty. Analysis of the receiver operating characteristic (ROC) curve corresponding to IL-8 showed an area under the curve of 0.7 (p = 0.003; 95% CI [0.58-0.81]) and a predictive threshold of 5.27 pg/ml. Positive correlations were found between frailty score, IL-6, and IL-8 levels. In addition, a significant positive correlation was observed between IL-8 levels and Timed Up and Go test results. However, a negative correlation was observed between Mini Nutritional Assessment Short-Form score, IL-6 and CRP levels, as well as between Activities of Daily Living score and serum levels of TNF-α, IL-6, and CRP. In conclusion, the key findings of this study collectively support a role of pro-inflammatory cytokines, TNF-α, CRP, and especially IL-8 in the development of frailty in older adults.
MeSH term(s)	Aged ; Aged, 80 and over ; Biomarkers/blood ; C-Reactive Protein/analysis ; Cross-Sectional Studies ; Cytokines/blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Frail Elderly ; Frailty/epidemiology ; Geriatric Assessment/methods ; Humans ; Inflammation/metabolism ; Interleukin-6/blood ; Interleukin-8/blood ; Male ; ROC Curve ; Tumor Necrosis Factor-alpha/blood ; Tunisia/epidemiology
Chemical Substances	Biomarkers ; CXCL8 protein, human ; Cytokines ; IL6 protein, human ; Interleukin-6 ; Interleukin-8 ; Tumor Necrosis Factor-alpha ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2020-11-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0242152
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