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

Abstract

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.

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

“…Dihydroethidine (DHE) is a fluorescent probe that measures ROS production (including superoxide anions (O 2 •− )) by flow cytometry [ 69 , 74 ]. Indeed, the non-fluorescent probe (DHE) is rapidly oxidized by ROS, once it enters the cell, and forms ethidium (HE) which binds to DNA and exhibits an orange/red fluorescence in response to a blue excitation (λEx Max = 488 nm; λEm Max = 575 nm).…”

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

“…This is because the majority of ROS is produced within the mitochondrial respiratory chain as byproducts of ATP generation [ 41 ], and the imbalance between ROS and antioxidants within the mitochondria might be one of the crucial pathways leading to its dysfunction, further triggering the oxidative stress cascade. A recent study reported that treating 158 N cells with C26:0 at concentrations of up to 20 µM for 24 and 48 h induced cell death due to mitochondrial dysfunction and oxidative stress [ 42 ].…”

Effect of docosahexaenoic acid on in vitro growth of bovine oocytes

“…Supplementation of male with fish oil drastically increased DHA contents in mitochondrial membrane of skeletal muscles. 33 DHA supplementation of the medium affects the cellular membrane 34 and is incorporated into the mitochondrial membrane, as determined by an increase in cardiolipin. 35 In addition, DHA increased MMP and susceptibility of the mitochondria to oxidative stress.…”