scholarly journals Drug-Induced Lipid Remodeling in Leishmania Parasites

2021 ◽  
Vol 9 (4) ◽  
pp. 790
Author(s):  
Sneider Alexander Gutierrez Guarnizo ◽  
Elena B. Tikhonova ◽  
Masoud Zabet-Moghaddam ◽  
Kai Zhang ◽  
Carlos Muskus ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Physiological Response ◽  
Long Chain Fatty Acids ◽  
Drug Induced ◽  
Intracellular Lipids ◽  
Before And After ◽  
Antileishmanial Drug ◽  
Leishmania Parasites ◽  
Long Chain ◽  
Potential Biomarkers

Leishmania parasites efficiently develop resistance against several types of drugs including antimonials, the primary antileishmanial drug historically implemented. The resistance to antimonials is considered to be a major risk factor for effective leishmaniasis treatment. To detect biomarkers/biopatterns for the differentiation of antimony-resistant Leishmania strains, we employed untargeted global mass spectrometry to identify intracellular lipids present in antimony sensitive and resistant parasites before and after antimony exposure. The lipidomic profiles effectively differentiated the sensitive and resistant phenotypes growing with and without antimony pressure. Resistant phenotypes were characterized by significant downregulation of phosphatidylcholines, sphingolipid decrease, and lysophosphatidylcholine increase, while sensitive phenotypes were characterized by the upregulation of triglycerides with long-chain fatty acids and a tendency toward the phosphatidylethanolamine decrease. Our findings suggest that the changes in lipid composition in antimony-resistant parasites contribute to the physiological response conducted to combat the oxidative stress unbalance caused by the drug. We have identified several lipids as potential biomarkers associated with the drug resistance.

scholarly journals Induction of Mitochondrial Changes Associated with Oxidative Stress on Very Long Chain Fatty Acids (C22:0, C24:0, or C26:0)-Treated Human Neuronal Cells (SK-NB-E)

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Amira Zarrouk ◽  
Anne Vejux ◽  
Thomas Nury ◽  
Hammam I. El Hajj ◽  
Madouda Haddad ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Cell Counting ◽  
Long Chain Fatty Acids ◽  
Superoxide Anion Production ◽  
Mitochondrial Dysfunctions ◽  
Whole Cells ◽  
Potential Risk Factors ◽  
Long Chain ◽  
Chain Fatty Acids

In Alzheimer's disease, lipid alterations point towards peroxisomal dysfunctions. Indeed, a cortical accumulation of saturated very long chain fatty acids (VLCFAs: C22:0, C24:0, C26:0), substrates for peroxisomalβ-oxidation, has been found in Alzheimer patients. This study was realized to investigate the effects of VLCFAs at the mitochondrial level since mitochondrial dysfunctions play crucial roles in neurodegeneration. On human neuronal SK-NB-E cells treated with C22:0, C24:0, or C26:0 (0.1–20 μM; 48 h), an inhibition of cell growth and mitochondrial dysfunctions were observed by cell counting with trypan blue, MTT assay, and measurement of mitochondrial transmembrane potential (Δψm) with DiOC6(3). A stimulation of oxidative stress was observed with DHE and MitoSOX used to quantify superoxide anion production on whole cells and at the mitochondrial level, respectively. With C24:0 and C26:0, by Western blotting, lower levels of mitochondrial complexes III and IV were detected. After staining with MitoTracker and by transmission electron microscopy used to study mitochondrial topography, mass and morphology, major changes were detected in VLCFAs treated-cells: modification of the cytoplasmic distribution of mitochondria, presence of large mitochondria, enhancement of the mitochondrial mass. Thus, VLCFAs can be potential risk factors contributing to neurodegeneration by inducing neuronal damages via mitochondrial dysfunctions.

scholarly journals N-Acetylcysteine Reverses the Mitochondrial Dysfunction Induced by Very Long-Chain Fatty Acids in Murine Oligodendrocyte Model of Adrenoleukodystrophy

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1826
Author(s):  
Jie Zhou ◽  
Marcia R. Terluk ◽  
Paul J. Orchard ◽  
James C. Cloyd ◽  
Reena V. Kartha
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Cell Death ◽  
Membrane Potential ◽  
Mitochondrial Dysfunction ◽  
Long Chain Fatty Acids ◽  
Specific Effects ◽  
Low Concentrations ◽  
Long Chain ◽  
Chain Fatty Acids

The accumulation of saturated very long-chain fatty acids (VLCFA, ≥C22:0) due to peroxisomal impairment leads to oxidative stress and neurodegeneration in X-linked adrenoleukodystrophy (ALD). Among the neural supporting cells, myelin-producing oligodendrocytes are the most sensitive to the detrimental effect of VLCFA. Here, we characterized the mitochondrial dysfunction and cell death induced by VLFCA, and examined whether N-acetylcysteine (NAC), an antioxidant, prevents the cytotoxicity. We exposed murine oligodendrocytes (158 N) to hexacosanoic acid (C26:0, 1–100 µM) for 24 h and measured reactive oxygen species (ROS) and cell death. Low concentrations of C26:0 (≤25 µM) induced a mild effect on cell survival with no alterations in ROS or total glutathione (GSH) concentrations. However, analysis of the mitochondrial status of cells treated with C26:0 (25 µM) revealed depletion in mitochondrial GSH (mtGSH) and a decrease in the inner membrane potential. These results indicate that VLCFA disturbs the mitochondrial membrane potential causing ROS accumulation, oxidative stress, and cell death. We further tested whether NAC (500 µM) can prevent the mitochondria-specific effects of VLCFA in C26:0-treated oligodendrocytes. Our results demonstrate that NAC improves mtGSH levels and mitochondrial function in oligodendrocytes, indicating that it has potential use in the treatment of ALD and related disorders.

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

2020 ◽  
Vol 21 (2) ◽  
pp. 641 ◽  
Author(s):  
Thomas Nury ◽  
Margaux Doria ◽  
Gérard Lizard ◽  
Anne Vejux
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Docosahexaenoic Acid ◽  
Membrane Integrity ◽  
Long Chain Fatty Acids ◽  
Western Blot Assay ◽  
Cytotoxic Effects ◽  
The Impact ◽  
Long Chain ◽  
Chain Fatty Acids

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.

Postprandial Activation of Coagulant Factor VII by Long-chain Dietary Fatty Acids

1996 ◽  
Vol 76 (03) ◽  
pp. 369-371 ◽  
Author(s):  
T A B Sanders ◽  
G J Miller ◽  
Tamara de Grassi ◽  
Najat Yahia
Keyword(s):  
Fatty Acids ◽  
Dietary Fatty Acids ◽  
Factor Vii ◽  
Fat Intake ◽  
Long Chain Fatty Acids ◽  
Postprandial Lipaemia ◽  
Increased Risk ◽  
Coagulant Activity ◽  
Long Chain Triglycerides ◽  
Long Chain

SummaryFactor VII coagulant activity (FVIIc) is associated with an increased risk of fatal ischaemic heart disease (IHD). Several reports have suggested that dietary fat intake or hypertriglyceridaemia are associated with elevated levels of FVII. This study demonstrates that an intake of long-chain fatty acids sufficient to induce postprandial lipaemia in healthy subjects leads to a substantial elevation in both FVIIc and the concentration of FVII circulating in the activated form. Such an increase in FVIIc could not be induced by medium-chain triglycerides. These results suggest that the consumption of a sufficient amount of long-chain triglycerides to induce postprandial lipaemia induces the activation of FVII.

Oxidative Stress Status in Patients with Choledocholithiasis: Before and After Endoscopic Sphincterotomy and Biliary Clearance

2018 ◽  
Vol 69 (8) ◽  
pp. 2172-2176
Author(s):  
Catalin Victor Sfarti ◽  
Alin Ciobica ◽  
Carol Stanciu ◽  
Gheorghe G. Balan ◽  
Irina Garleanu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoscopic Sphincterotomy ◽  
Specific Activity ◽  
Oxidative Stress Marker ◽  
Control Group ◽  
Oxidative Stress Parameter ◽  
Extrahepatic Cholestasis ◽  
Biliary Clearance ◽  
Oxidative Stress Status ◽  
Before And After

Choledocholithiasis may cause biliary obstruction which leads to hepatocellular injury. Oxidative stress has been proposed as a possible mechanism involved in this disorder. This study evaluates the oxidative stress burden in patients with choledocholithiasis and secondary cholestasis, before and after endoscopic sphincterotomy. Experimental part: Patients diagnosed with choledocholithiasis and secondary extrahepatic cholestasis were included in the study between January 1st 2016 and October 31st 2016. In all patients oxidative stress markers were collected within 2 hours before and 48 hours after therapeutic ERCP. Selected markers were superoxide dismutase (SOD), glutathione peroxidase (GPX) and malondialdehyde (MDA). The results were compared to those from a group of 40 healthy subjects. Significantly lower concentrations of SOD (p = 0.03) and GPX (p [ 0.0001) activities, associated with an increased level of MDA level (p [ 0.0001) were shown in patients before biliary clearance compared with the healthy control group. After ERCP the only oxidative stress parameter which showed improvement was the SOD specific activity (p = 0.037). This study shows that extrahepatic cholestasis secondary to choledocholithiasis is associated with increased oxidative stress status. After biliary clearance one oxidative stress marker was significantly improved (SOD), suggesting a possible antioxidant effect of such procedure.

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