Idebenone protects against oxidized low density lipoprotein induced mitochondrial dysfunction in vascular endothelial cells via GSK3β/β-catenin signalling pathways

Lin, Pengfei; Liu, Junling; Ren, Ming; Ji, Kunqian; Li, Ling; Zhang, Bin; Gong, Yaoqin; Yan, Chuanzhu

doi:10.1016/j.bbrc.2015.08.058

Cited by 32 publications

(19 citation statements)

References 22 publications

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“…Apart from this study, there is general agreement that at least micromolar, sometimes up to millimolar idebenone concentrations, combined with a test system that converts idebenone to the hydroquinone form, are required to see any direct antioxidant activity [ 26 , 42 , 44 ]. In contrast to cell-free studies, the majority of studies that reported “antioxidant activity” in cell culture used extended preincubation times with idebenone, typically overnight or over several days despite the fact that idebenone penetrates cells within a few minutes [ [45] , [46] , [47] ]. Although the majority of studies used concentrations in the low micromolar range, some surprisingly reported protective effects against ROS-induced toxicity at nanomolar concentrations [ 45 , 47 ] which are, unlike micromolar concentrations, drug concentrations that can be achieved in vivo .…”

Section: Is Idebenone a Direct Antioxidant?mentioning

confidence: 99%

“…In a model of galactose-induced cataract formation idebenone reduced oxidative damage by increasing total endogenous tissue antioxidant capacity [ 56 ]. This increased antioxidant capacity by idebenone is likely the consequence of an increased expression of a range of endogenous antioxidants such as superoxide dismutase (SOD), catalase, NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione (GSH), and glutathione peroxidase (GPx) [ 37 , 45 , 48 , 49 , 57 ], while also downregulating the superoxide-producing enzyme NOX2 [ 58 ]. Interestingly, some of the antioxidant genes reported to be activated by idebenone such as SOD, NQO1 and GPx are controlled by the transcription factor Nrf2.…”

Section: Is Idebenone a Direct Antioxidant?mentioning

confidence: 99%

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Idebenone: When an antioxidant is not an antioxidant

et al. 2021

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Idebenone is a well described drug that was initially developed against dementia. The current literature widely portrays this molecule as a potent antioxidant and CoQ 10 analogue. While numerous papers seem to support this view, a closer look indicates that the pharmacokinetics of idebenone do not support these claims. A major discrepancy between achievable tissue levels, especially in target tissues such as the brain, and doses required to show the proposed effects, significantly questions our current understanding. This review explains how this has happened and highlights the discrepancies in the current literature. More importantly, based on some recent discoveries, a new framework is presented that can explain the mode of action of this molecule and can align formerly contradictory results. Finally, this new appreciation of the molecular activities of idebenone provides a rational approach to test idebenone in novel indications that might have not been considered previously for this drug.

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Section: Is Idebenone a Direct Antioxidant?mentioning

confidence: 99%

Section: Is Idebenone a Direct Antioxidant?mentioning

confidence: 99%

Idebenone: When an antioxidant is not an antioxidant

et al. 2021

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“…Furthermore, oxidation may cause a decrease in the amount of nitric oxide (NO) and thus induce dysfunction of the endothelium [8]. Indeed, in a recent study, oxidative stress was found to promote apoptosis and result in the death of endothelial cells [9]. Endothelial cells participate and play an important role in the prevention of inflammation, regulate vascular tone, and maintain the balance between coagulation and anticoagulation.…”

Section: The Role Of Oxidative Stress In Endothelial Cells In Physmentioning

confidence: 99%

Research Progress on Signaling Pathway-Associated Oxidative Stress in Endothelial Cells

Liang

Lin

et al. 2017

Oxidative Medicine and Cellular Longevity

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Studying the mechanisms of oxidative stress in endothelial cells is vital to the discovery of novel drugs for the treatment of cardiovascular disease. This article reviews the progress within the field of the role of oxidative responses in the physiology and growth of endothelial cells and emphasizes the effects of several main signal pathways involved in the oxidative stress of endothelial cells. Herein, we aim to provide scientific direction that can serve as a basis for researchers specializing in the signaling pathway of oxidative stress.

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“…A recent study shed light on the mechanism of action of IDE and provided more insights into its possible therapeutic use for treating or preventing atherosclerosis by ameliorating mitochondrial dysfunctions in endothelial cells [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Idebenone: Novel Strategies to Improve Its Systemic and Local Efficacy

et al. 2018

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The key role of antioxidants in treating and preventing many systemic and topical diseases is well recognized. One of the most potent antioxidants available for pharmaceutical and cosmetic use is Idebenone (IDE), a synthetic analogue of Coenzyme Q10. Unfortunately, IDE’s unfavorable physicochemical properties such as poor water solubility and high lipophilicity impair its bioavailability after oral and topical administration and prevent its parenteral use. In recent decades, many strategies have been proposed to improve IDE effectiveness in the treatment of neurodegenerative diseases and skin disorders. After a brief description of IDE potential therapeutic applications and its pharmacokinetic and pharmacodynamic profile, this review will focus on the different approaches investigated to overcome IDE drawbacks, such as IDE incorporation into different types of delivery systems (liposomes, cyclodextrins, microemulsions, self-micro-emulsifying drug delivery systems, lipid-based nanoparticles, polymeric nanoparticles) and IDE chemical modification. The results of these studies will be illustrated with emphasis on the most innovative strategies and their future perspectives.

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Idebenone protects against oxidized low density lipoprotein induced mitochondrial dysfunction in vascular endothelial cells via GSK3β/β-catenin signalling pathways

Cited by 32 publications

References 22 publications

Idebenone: When an antioxidant is not an antioxidant

Idebenone: When an antioxidant is not an antioxidant

Research Progress on Signaling Pathway-Associated Oxidative Stress in Endothelial Cells

Idebenone: Novel Strategies to Improve Its Systemic and Local Efficacy

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