Effects of dietary linoleic acid and gamma linolenic acid on platelets of patients with multiple sclerosis

McGregor, Lilian; Smith, Anthony D.; Sidey, M C; Belin, J; Zilkha, K. J.; McGregor, John L.

doi:10.1111/j.1600-0404.1989.tb03837.x

Cited by 10 publications

(5 citation statements)

References 23 publications

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“…There has been a considerable interest in the possible role of unsaturated fatty acids in MS [34,35] leading to dietary intervention trials [36][37][38][39][40]. MS patients have sig nificantly lower proportions of linoleic and arachidonic acids in most of their erythrocyte phospholipids, with a compensatory increase in saturated fatty acids [41], Also, the concentration of linoleic acid is significantly lower in white blood cells and platelets in MS patients compared to controls [42], The blood level of various substances may be altered by the dietary intake.…”

Section: Discussionmentioning

confidence: 99%

Influence of Fatty Acid Content of Lysophosphatidyl Choline on Its Myelinotoxic Properties

Sedal

Jennings²,

Allt³

et al. 1992

Eur Neurol

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The efficacy of lysophosphatidyl choline (LPC) type I and type IV in producing demyelination was assessed in rat tibial and sural nerve. By light and electron microscopy, a greater myelinolytic activity was demonstrated with type I, and concomitantly electrophysiology showed a more severe conduction block. In teased nerve preparations and 1-um thin sections, demyelinated fibres were more frequent with LPC type I. At 1 h after injection, electron microscopy showed much more extensive myelin lysis in the form of fine vesicular debris. By 6 days, completely demyelinated fibres were much more common and associated Schwann cells contained either small quantities or no myelin debris. With type IV LPC, cytopathological changes were more extensive at 1 h. A minority of Schwann cells showed swollen hydropic cytoplasm and degradation of organelles. Axonal retraction from the myelin sheath occurred in occasional fibres, and in a few unmyelinated fibres axoplasm showed organelle depletion and increased granularity. By 6 days, Schwann cells still contained large quantities of gross myelin debris and had often retracted to expose extensive areas of axolemma. The findings suggest that the two types of LPC have different myelinolytic actions, which may be related to their different fatty acid content. A possible role for the two types of LPC in ‘bystander demyelination’ is considered.

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Section: Discussionmentioning

confidence: 99%

Influence of Fatty Acid Content of Lysophosphatidyl Choline on Its Myelinotoxic Properties

Sedal

Jennings²,

Allt³

et al. 1992

Eur Neurol

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“…Halliwell and colleagues had suggested that metal ion release could be an important mechanism for the neurotoxicity of L-DOPA and related metabolites (Spencer et al, 1994). Further, transition metal ions have been reported to promote the toxicity of catechols, including L-DOPA (Halliwell, 2009, 1989). It has also been ascertained that the labile concentrations of copper are elevated in various malignancies (García et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Copper-mediated DNA damage by the neurotransmitter dopamine and L-DOPA: A pro-oxidant mechanism

Rehmani

Zafar

Arif

et al. 2017

Toxicology in Vitro

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Oxidative DNA damage has been implicated in the pathogenesis of neurological disorders, cancer and ageing. Owing to the established link between labile copper concentrations and neurological diseases, it is critical to explore the interactions of neurotransmitters and drug supplements with copper. Herein, we investigate the pro-oxidant DNA damage induced by the interaction of L-DOPA and dopamine (DA) with copper. The DNA binding affinity order of the compounds has been determined by in silico molecular docking. Agarose gel electrophoresis reveals that L-DOPA and DA are able to induce strand scission in plasmid pcDNA3.1 (+/−) in a copper dependent reaction. These metabolites also cause cellular DNA breakage in human lymphocytes by mobilizing endogenous copper, as assessed by comet assay. Further, L-DOPA and DA-mediated DNA breaks were detected by the appearance of post-DNA damage sensitive marker γH2AX in cancer cell lines accumulating high copper. Immunofluorescence demonstrated the co-localization of downstream repair factor 53BP1 at the damaged induced γH2AX foci in cancer cells. The present study corroborates and provides a mechanism to the hypothesis that suggests metal-mediated oxidation of catecholamines contributes to the pathogenesis of neurodegenerative diseases.

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“…However, its extreme insolubility in water poses a serious limitation to distribution in the aqueous biological environment, limiting its usefulness as a therapeutic intervention. Efforts to make α-tocopherol more water soluble by replacing the lipophilic phytyl chain with more hydrophilic moieties interfere with its antioxidant capabilities and may incur unexpected adverse biological effects [46], [77]. Thus, unmodified α-tocopherol was used in the formulation of the nanoprodrug as a stabilizing and size reducing structural component, in addition to its antioxidant benefits.…”

Section: Discussionmentioning

confidence: 99%

Reactive Oxygen Species-Activated Nanoprodrug of Ibuprofen for Targeting Traumatic Brain Injury in Mice

Clond

Lee

et al. 2013

PLoS ONE

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Traumatic brain injury (TBI) is an enormous public health problem, with 1.7 million new cases of TBI recorded annually by the Centers for Disease Control. However, TBI has proven to be an extremely challenging condition to treat. Here, we apply a nanoprodrug strategy in a mouse model of TBI. The novel nanoprodrug contains a derivative of the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen in an emulsion with the antioxidant α-tocopherol. The ibuprofen derivative, Ibu2TEG, contains a tetra ethylene glycol (TEG) spacer consisting of biodegradable ester bonds. The biodegradable ester bonds ensure that the prodrug molecules break down hydrolytically or enzymatically. The drug is labeled with the fluorescent reporter Cy5.5 using nonbiodegradable bonds to 1-octadecanethiol, allowing us to reliably track its accumulation in the brain after TBI. We delivered a moderate injury using a highly reproducible mouse model of closed-skull controlled cortical impact to the parietal region of the cortex, followed by an injection of the nanoprodrug at a dose of 0.2 mg per mouse. The blood brain barrier is known to exhibit increased permeability at the site of injury. We tested for accumulation of the fluorescent drug particles at the site of injury using confocal and bioluminescence imaging of whole brains and brain slices 36 hours after administration. We demonstrated that the drug does accumulate preferentially in the region of injured tissue, likely due to an enhanced permeability and retention (EPR) phenomenon. The use of a nanoprodrug approach to deliver therapeutics in TBI represents a promising potential therapeutic modality.

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Effects of dietary linoleic acid and gamma linolenic acid on platelets of patients with multiple sclerosis

Cited by 10 publications

References 23 publications

Influence of Fatty Acid Content of Lysophosphatidyl Choline on Its Myelinotoxic Properties

Influence of Fatty Acid Content of Lysophosphatidyl Choline on Its Myelinotoxic Properties

Copper-mediated DNA damage by the neurotransmitter dopamine and L-DOPA: A pro-oxidant mechanism

Reactive Oxygen Species-Activated Nanoprodrug of Ibuprofen for Targeting Traumatic Brain Injury in Mice

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