Impact of Oxysterols in Age-Related Disorders and Strategies to Alleviate Adverse Effects.

Oxysterols or cholesterol oxidation products are a class of molecules with the sterol moiety, derived from oxidative reaction of cholesterol through enzymatic and non-enzymatic processes. They are widely reported in animal-origin foods and prove significant involvement in the regulation of cholesterol homeostasis, lipid transport, cellular signaling, and other physiological processes. Reports of oxysterol-mediated cytotoxicity are in abundance and thus consequently implicated in several age-related and lifestyle disorders such as cardiovascular diseases, bone disorders, pancreatic disorders, age-related macular degeneration, cataract, neurodegenerative disorders such as Alzheimer's and Parkinson's disease, and some types of cancers. In this chapter, we attempt to review a selection of physiologically relevant oxysterols, with a focus on their formation, properties, and roles in health and disease, while also delving into the potential of natural and synthetic molecules along with bacterial enzymes for mitigating oxysterol-mediated cell damage.

Exploring the Role of Apigenin in Neuroinflammation: Insights and Implications.

Neuroinflammation, a hallmark of various central nervous system disorders, is often associated with oxidative stress and neuronal or oligodendrocyte cell death. It is therefore very interesting to target neuroinflammation pharmacologically. One therapeutic option is the use of nutraceuticals, particularly apigenin. Apigenin is present in plants: vegetables (parsley, celery, onions), fruits (oranges), herbs (chamomile, thyme, oregano, basil), and some beverages (tea, beer, and wine). This review explores the potential of apigenin as an anti-inflammatory agent across diverse neurological conditions (multiple sclerosis, Parkinson's disease, Alzheimer's disease), cancer, cardiovascular diseases, cognitive and memory disorders, and toxicity related to trace metals and other chemicals. Drawing upon major studies, we summarize apigenin's multifaceted effects and underlying mechanisms in neuroinflammation. Our review underscores apigenin's therapeutic promise and calls for further investigation into its clinical applications.

Characterization of Cell Death Induced by Imine Analogs of Trans-Resveratrol: Induction of Mitochondrial Dysfunction and Overproduction of Reactive Oxygen Species Leading to, or Not, Apoptosis without the Increase in the S-Phase of the Cell Cycle.

Trans-resveratrol (RSV) is a non-flavonoid polyphenol (stilbene) with numerous biological activities, such as anti-tumor activities. However, RSV is rapidly metabolized, which limits its therapeutic use. The availability of RSV analogues with similar activities for use in vivo is therefore a major challenge. For this purpose, several isomeric analogues of RSV, aza-stilbenes (AZA-ST 1a-g), were synthesized, and their toxicities were characterized and compared to those of RSV on murine N2a neuronal cells using especially flow cytometric methods. All AZA-ST 1a-g have an inhibitory concentration 50 (IC50) between 11.3 and 25 µM when determined by the crystal violet assay, while that of RSV is 14.5 µM. This led to the characterization of AZA-ST 1a-g-induced cell death, compared to RSV, using three concentrations encompassing the IC50s (6.25, 12.5 and 25 µM). For AZA-ST 1a-g and RSV, an increase in plasma membrane permeability to propidium iodide was observed, and the proportion of cells with depolarized mitochondria measured with DiOC6(3) was increased. An overproduction of reactive oxygen species (ROS) was also observed on whole cells and at the mitochondrial level using dihydroethidium and MitoSox Red, respectively. However, only RSV induced a mode of cell death by apoptosis associated with a marked increase in the proportion of cells with condensed and/or fragmented nuclei (12.5 µM: 22 ± 9%; 25 µM: 80 ± 10%) identified after staining with Hoechst 33342 and which are characteristic of apoptotic cells. With AZA-ST, a slight but significant increase in the percentage of apoptotic cells was only detected with AZA-ST 1b (25 µM: 17 ± 1%) and AZA-ST 1d (25 µM: 26 ± 4%). Furthermore, only RSV induced significant cell cycle modifications associated with an increase in the percentage of cells in the S phase. Thus, AZA-ST 1a-g-induced cell death is characterized by an alteration of the plasma membrane, an induction of mitochondrial depolarization (loss of ΔΨm), and an overproduction of ROS, which may or may not result in a weak induction of apoptosis without modification of the distribution of the cells in the different phases of the cell cycle.

Protective Effect of Nopal Cactus (Opuntia ficus-indica) Seed Oil against Short-Term Lipopolysaccharides-Induced Inflammation and Peroxisomal Functions Dysregulation in Mouse Brain and Liver.

Exposure to endotoxins (lipopolysaccharides, LPS) may lead to a potent inflammatory cytokine response and a severe impairment of metabolism, causing tissue injury. The protective effect provided by cactus seed oil (CSO), from Opuntia ficus-indica, was evaluated against LPS-induced inflammation, dysregulation of peroxisomal antioxidant, and ß-oxidation activities in the brain and the liver. In both tissues, a short-term LPS exposure increased the proinflammatory interleukine-1ß (Il-1ß), inducible Nitroxide synthase (iNos), and Interleukine-6 (Il-6). In the brain, CSO action reduced only LPS-induced iNos expression, while in the liver, CSO attenuated mainly the hepatic Il-1ß and Il-6. Regarding the peroxisomal antioxidative functions, CSO treatment (as Olive oil (OO) or Colza oil (CO) treatment) induced the hepatic peroxisomal Cat gene. Paradoxically, we showed that CSO, as well as OO or CO, treatment can timely induce catalase activity or prevent its induction by LPS, respectively, in both brain and liver tissues. On the other hand, CSO (as CO) pretreatment prevented the LPS-associated Acox1 gene and activity decreases in the liver. Collectively, CSO showed efficient neuroprotective and hepato-protective effects against LPS, by maintaining the brain peroxisomal antioxidant enzyme activities of catalase and glutathione peroxidase, and by restoring hepatic peroxisomal antioxidant and ß-oxidative capacities.

Cytotoxic and Antioxidant Activities of Imine Analogs of Trans-Resveratrol towards Murine Neuronal N2a Cells.

Trans-resveratrol is a natural polyphenol showing numerous biological properties, especially anti-tumoral and antioxidant activity. Among numerous resveratrol derivatives, aza-stilbenes, which bear an imine bound, show interesting biological activities. In the present study, we synthesized a series of imine analogs of trans-resveratrol (seven aza-stilbenes) following an easy and low-cost procedure of green chemistry. The toxicity of synthesized aza-stilbenes, which is currently unknown, was evaluated on murine neuronal N2a cells, comparatively to trans-resveratrol, by considering: cell density evaluated by staining with sulforhodamine 101; esterase activity, which is a criteria of cell viability, by staining with fluorescein diacetate; and transmembrane mitochondrial potential, which is known to decrease during cell death, by staining with DiOC6(3) using flow cytometry. In addition, the antioxidant activity was quantified with the KRL (Kit Radicaux Libres) assay, the DPPH (2,2'-diphenyl-1-picrylhydrazyl radical) assay and the FRAP (ferric reducing antioxidant power) assay. The PAOT (Pouvoir Antioxidant Total) score was also used. The aza-stilbenes provide different cytotoxic and antioxidant activities, which are either higher or lower than those of trans-resveratrol. Based on their cytotoxic and antioxidant characteristics, all synthesized aza-stilbenes are distinguished from trans-resveratrol.

Involvement of Microglia in Neurodegenerative Diseases: Beneficial Effects of Docosahexahenoic Acid (DHA) Supplied by Food or Combined with Nanoparticles.

Neurodegenerative diseases represent a major public health issue and require better therapeutic management. The treatments developed mainly target neuronal activity. However, an inflammatory component must be considered, and microglia may constitute an important therapeutic target. Given the difficulty in developing molecules that can cross the blood-brain barrier, the use of food-derived molecules may be an interesting therapeutic avenue. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (22:6 omega-3), has an inhibitory action on cell death and oxidative stress induced in the microglia. It also acts on the inflammatory activity of microglia. These data obtained in vitro or on animal models are corroborated by clinical trials showing a protective effect of DHA. Whereas DHA crosses the blood-brain barrier, nutritional intake lacks specificity at both the tissue and cellular level. Nanomedicine offers new tools which favor the delivery of DHA at the cerebral level, especially in microglial cells. Because of the biological activities of DHA and the associated nanotargeting techniques, DHA represents a therapeutic molecule of interest for the treatment of neurodegenerative diseases.

Polyphenols of the Mediterranean Diet and Their Metabolites in the Prevention of Colorectal Cancer.

The Mediterranean diet is a central element of a healthy lifestyle, where polyphenols play a key role due to their anti-oxidant properties, and for some of them, as nutripharmacological compounds capable of preventing a number of diseases, including cancer. Due to the high prevalence of intestinal cancer (ranking second in causing morbidity and mortality), this review is focused on the beneficial effects of selected dietary phytophenols, largely present in Mediterranean cooking: apigenin, curcumin, epigallocatechin gallate, quercetin-rutine, and resveratrol. The role of the Mediterranean diet in the prevention of colorectal cancer and future perspectives are discussed in terms of food polyphenol content, the effectiveness, the plasma level, and the importance of other factors, such as the polyphenol metabolites and the influence of the microbiome. Perspectives are discussed in terms of microbiome-dependency of the brain-second brain axis. The emergence of polyphenol formulations may strengthen the efficiency of the Mediterranean diet in the prevention of cancer.

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

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 7ß-hydroxycholesterol (7ß-OHC). These observations led to the demonstration that 7KC and 7ß-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 7ß-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.

Potential Involvement of Peroxisome in Multiple Sclerosis and Alzheimer's Disease : Peroxisome and Neurodegeneration.

Peroxisomopathies are rare diseases due to dysfunctions of the peroxisome in which this organelle is either absent or with impaired activities. These diseases, at the exception of type I hyperoxaluria and acatalasaemia, affect the central and peripheral nervous system. Due to the significant impact of peroxisomal abnormalities on the functioning of nerve cells, this has led to an interest in peroxisome in common neurodegenerative diseases, such as Alzheimer's disease and multiple sclerosis. In these diseases, a role of the peroxisome is suspected on the basis of the fatty acid and phospholipid profile in the biological fluids and the brains of patients. It is also speculated that peroxisomal dysfunctions could contribute to oxidative stress and mitochondrial alterations which are recognized as major players in the development of neurodegenerative diseases. Based on clinical and in vitro studies, the data obtained support a potential role of peroxisome in Alzheimer's disease and multiple sclerosis.

Lipids Nutrients in Parkinson and Alzheimer's Diseases: Cell Death and Cytoprotection.

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.

Docosahexaenoic Acid Attenuates Mitochondrial Alterations and Oxidative Stress Leading to Cell Death Induced by Very Long-Chain Fatty Acids in a Mouse Oligodendrocyte Model.

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.

Aza- and Azo-Stilbenes: Bio-Isosteric Analogs of Resveratrol.

Several series of natural polyphenols are described for their biological and therapeutic potential. Natural stilbenoid polyphenols, such as trans-resveratrol, pterostilbene and piceatannol are well-known for their numerous biological activities. However, their moderate bio-availabilities, especially for trans-resveratrol, prompted numerous research groups to investigate innovative and relevant synthetic resveratrol derivatives. This review is focused on isosteric resveratrol analogs aza-stilbenes and azo-stilbenes in which the C=C bond between both aromatic rings was replaced with C=N or N=N bonds, respectively. In each series, synthetic ways will be displayed, and structural sights will be highlighted and compared with those of resveratrol. The biological activities of some of these molecules will be presented as well as their potential therapeutic applications. In some cases, structure-activity relationships will be discussed.

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.

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.

Prevention of 7-ketocholesterol-induced side effects by natural compounds.

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.

Peroxisomes in Immune Response and Inflammation.

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.

Octadecaneuropeptide (ODN) Induces N2a Cells Differentiation through a PKA/PLC/PKC/MEK/ERK-Dependent Pathway: Incidence on Peroxisome, Mitochondria, and Lipid Profiles.

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.

Correlation of trans fatty acids with the severity of coronary artery disease lesions.

BACKGROUND: Nutritional choices, which include the source of dietary fatty acids (FA), have an important significant impact on coronary artery disease (CAD). We aimed to determine on patients with CAD the relationships between Trans fatty acids (Trans FA) and different CAD associated parameters such as inflammatory and oxidative stress parameters in addition to Gensini score as a vascular severity index. METHODS: Fatty acid profiles were established by gas chromatography from 111 CAD patients compared to 120 age-matched control group. Lipid peroxidation biomarkers, oxidative stress, inflammatory parameters and Gensini score were studied. RESULTS: Our study showed a significant decrease of the antioxidant parameters levels such as erythrocyte glutathione peroxydase (GPx) and superoxide dismutase (SOD) activities, plasma antioxidant status (FRAP) and thiol (SH) groups in CAD patients. On the other hand, catalase activity, conjugated dienes and malondialdehyde were increased. Plasmatic and erythrocyte Trans FA were also increased in CAD patients compared to controls. Furthermore, divergent associations of these Trans FA accumulations were observed with low-density lipoprotein-cholesterol/ high-density lipoprotein-cholesterol (LDL-C/HDL-C) ratio, Apolipoprotein B (ApoB), lipid peroxidation parameters, high-sensitivity C Reactive Protein (hs-CRP), Interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and Gensini score. Especially, elaidic acid (C18:1 trans 9), trans C18:2 isomers and trans 11 eicosanoic acid are correlated with these parameters. Trans FA are also associated with oxidative stress, confirmed by a positive correlation between C20:1 trans 11 and GPx in erythrocytes. CONCLUSIONS: High level of Trans FA was highly associated with the induction of inflammation, oxidative stress and lipoperoxidation which appear to be based on the vascular severity and might be of interest to assess the stage and progression of atherosclerosis. The measurement of these Trans FA would be of great value for the screening of lipid metabolism disorders in CAD patients.

Identification of long and very long chain fatty acids, plasmalogen-C16:0 and phytanic acid as new lipid biomarkers in Tunisian coronary artery disease patients.

Long and very long chain fatty acids (LCFAs and VLCFAs) may play an active role in coronary artery diseases (CAD) etiology. Our aim was to evaluate the associations between LCPUFAs (C20:4n-6; C20:5n-3 and C22:6n-3) and VLCSFAs (C22:0, C24:0; and C26:0), as well as markers of peroxisomal integrity evaluated by phytanic acid and plasmalogen-C16:0 (PL-C16:0) in addition to the markers of lipid peroxidation (malondialdehyde [MDA] and conjugated dienes [CD]) and inflammation (high sensitivity C-reactive protein [hs-CRP]) with vascular severity evaluated by Gensini score in order to determine their possible effects on CAD in Tunisian population. Lipidomic strategy based on GC/MS-SIM was used to quantify LCPUFAs, VLCSFAs, and PL-C16:0 in red blood cells of CAD patients, non-CAD patients, and controls. We observed a significant increase in phytanic acid, PL-C16:0 and VLCFAs, particularly C26:0, in CAD group compared to controls. Further our findings showed positive correlations of C26:0 with MDA and with vascular severity score (Gensini score). In addition, a significant negative correlation was shown between hs-CRP and C22:6 n-3 (r=-0.297; p=0.002) and a significant positive association was observed between hs-CRP and C20:4 n-6 levels (r=0.196; p=0.039). Our results show changes in LCPUFAs and VLCSFAs concentrations in RBC among study groups, and suggest alterations in fatty acids metabolism regulated by elongase and desaturase enzymes. The positive correlations of C20:4n-6 and the negative correlations of C22:6n-3, simultaneously with Gensini score and hs-CRP, suggest a link of both inflammation and vascular severity complication of CAD with LCPUFAs and VLCSFAs. Induction of lipid oxidation, can be one of the outcomes of LCFAs and VLCFAs accumulation in vascular tissues and, thus, playing an important role in the pathogenesis of atherosclerosis. Quantification of LCPUFAs and VLCSFAs, phytanic acid and PL-C16:0 simultaneously, would be of great value for the screening of peroxisomal disorders in vascular tissue of CAD patients.

Association of plasma fatty acid alteration with the severity of coronary artery disease lesions in Tunisian patients.

BACKGROUND: Some factors related to diet are known to be involved in the progression of atherosclerosis in humans. METHODS: The relationship between plasma fatty acid (FA) levels and the severity of coronary artery disease (CAD), evaluated by Gensini score (GS), was investigated in CAD Tunisian patients compared to controls. Lipid profiles were analyzed, GS was calculated in CAD and non-CAD patients and compared to controls. RESULTS: CAD patients showed an alteration of conventional lipid parameters. In fact, a significant increase of plasmatic triglycerides (TG) level, atherogenic lipid ratios (TC/HDL-C,TG/HDL-C, LDL-C/HDL-C); and ApoB/ApoA1 was observed in the CAD group comparatively to controls (p < 0.001). Gensini score was showed to be a good indicator to evaluate cholesterol metabolism disorders associated with HDL-C since a negative association was found between HDL-C levels and GS for the two groups of patients. In addition, in the relation with FA and classes of FA, a negative association was found as expected, between Gensini score and total MUFA, PUFA n-3, total PUFA, GLA, DGLA and DHA. Furthermore, a positive association with stearic and erucic acid was found. Suggests that, GS is also a good indicator to evaluate FA metabolic disorders. Higher elongation index and modifications of desaturation index (D5D, D6D and D9D) were observed in patients compared to controls, supporting FA metabolism modifications. CONCLUSIONS: In conclusion, although that Tunisian population appears to follow the Mediterranean diet, variations of plasmatic FA levels and desaturase activities in CAD patients highlights an alteration of FA metabolism and suggests an important implication of certain FA in the development of atherosclerosis.

Tunisian Milk Thistle: An Investigation of the Chemical Composition and the Characterization of Its Cold-Pressed Seed Oils.

In this study, milk thistle seeds growing in different areas in Tunisia were cold pressed and the extracted oils were examined for their chemical and antioxidant properties. The major fatty acids were linoleic acid (C18:2) (57.0%, 60.0%, and 60.3% for the milk thistle seed oils native to Bizerte, Zaghouan and Sousse, respectively) and oleic acid (C18:1) (15.5%, 21.5%, and 22.4% for the milk thistle seed oils originating from Bizerte, Zaghouan and Sousse, respectively). High performance liquid chromatography (HPLC) analysis showed the richness of the milk thistle seed oils (MTSO) in α-tocopherol. The highest content was recorded for that of the region of Zaghouan (286.22 mg/kg). The total phenolic contents (TPC) of Zaghouan, Bizerte, and Sousse were 1.59, 8.12, and 4.73 Gallic Acid Equivalent (GAE) mg/g, respectively. Three phenolic acids were also identified (vanillic, p-coumaric, and silybine), with a predominance of the vanillic acid. The highest value was recorded for the Zaghouan milk thistle seed oil (83 mg/100 g). Differences in outcomes between regions may be due to climatic differences in areas. Zaghouan's cold-pressed milk thistle seed oil had a better quality than those of Bizerte and Sousse, and can be considered as a valuable source for new multi-purpose products or by-products for industrial, cosmetic, and pharmaceutical utilization.