Oxidative stress and antioxidant treatment in patients with peripheral artery disease

Koutakis, Panagiotis; Ismaeel, Ahmed; Farmer, Patrick J.; Purcell, Seth T.; Smith, Robert S.; Eidson, Jack L.; Bohannon, W. Todd

doi:10.14814/phy2.13650

Cited by 43 publications

(38 citation statements)

References 108 publications

(203 reference statements)

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“…5 However, the results of clinical studies regarding potential effects of antioxidant administration are disappointing, questioning the relevance of the preclinical hind limb ischaemia models in other situations. 5,6 Conversely, recent studies revealed that some pharmacological targets remain effective even in the presence of hypercholesterolaemia. 19 Thus, pharmacological inhibition of GSK3b allowed muscle protection in both normal and hypercholesterolaemic rats.…”

Section: Discussionmentioning

confidence: 99%

“…2,3 Such antioxidant strategies have thus been considered as promising therapeutic targets, but clinical results have been mostly disappointing and antioxidant therapies are still far from being integrated into treatment algorithms for peripheral arterial disease, despite promising preclinical efficacy. 1,5,6 This discrepancy has brought into question the relevance of the preclinical hind limb ischaemia models that were used for efficacy testing. 7 Thus, although this CLI model can be considered to be relevant to CLI, it does not entirely reproduce the complex human condition and there are important limitations that should be taken into account.…”

Section: Introductionmentioning

confidence: 99%

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Critical Limb Ischaemia Exacerbates Mitochondrial Dysfunction in ApoE–/– Mice Compared with ApoE+/+ Mice, but N-acetyl Cysteine still Confers Protection

Lejay

Charles

Georg

et al. 2019

European Journal of Vascular and Endovascular Surgery

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The study shows that critical limb ischaemia (CLI) exacerbates mitochondrial dysfunction and that antioxidant therapies such as N-acetyl cysteine (NAC) still confer protection, even if comorbidities are known to reduce the protective effects of many drugs. Clinical studies using antioxidant strategies have been mostly disappointing and antioxidant therapies are still far from being integrated into treatment algorithms for peripheral arterial disease, but these results suggest that oxidative stress needs to be considered as a target for protective strategies in the setting of CLI. Objectives: The current study was performed in order to determine the influence of hypercholesterolaemia on critical limb ischaemia (CLI) and whether targeting oxidative stress by antioxidant therapies such as N-acetyl cysteine (NAC), considered to be a direct scavenger of reactive oxygen species, could confer muscle protection. Methods: Apolipoprotein E (ApoE)e/e mice (n ¼ 9, 29 weeks old) and their genetic controls ApoEþ/þ mice (n ¼ 9, 29 weeks old) were submitted to sequential right femoral and iliac ligations; the left limb served as control. ApoEþ/þ mice were divided into two groups: Group 1 (n ¼ 4) and Group 2 (n ¼ 5); as well as ApoEe/e mice: Group 3 (n ¼ 3), and Group 4 (n ¼ 6). NAC treatment was administered to Groups 2 and 4 in drinking water. Mice were sacrificed on Day 40 and gastrocnemius muscles were harvested to study mitochondrial respiration by oxygraphy, calcium retention capacity by spectrofluorometry, and production of reactive oxygen species by electron paramagnetic resonance. Results: CLI associated with ApoE deficiency resulted in more severe mitochondrial dysfunction: maximum oxidative capacity and calcium retention capacity were decreased (À42.9% vs. À25.1%, p ¼ .010; and À73.1% vs. À40.3%, p ¼ .003 respectively) and production of reactive oxygen species was enhanced (þ63.6% vs. þ41.4%, p ¼ .03) in ApoEe/e mice compared with ApoEþ/þ mice respectively. Antioxidant treatment restored oxidative capacity, calcium retention capacity and decreased production of reactive oxygen species in both mice strands. Conclusions: In this small murine study, hypercholesterolaemia exacerbated mitochondrial dysfunction, as clinically expected; but antioxidant therapy appeared protective, which is counter to clinical experience. Further work is clearly needed.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Critical Limb Ischaemia Exacerbates Mitochondrial Dysfunction in ApoE–/– Mice Compared with ApoE+/+ Mice, but N-acetyl Cysteine still Confers Protection

Lejay

Charles

Georg

et al. 2019

European Journal of Vascular and Endovascular Surgery

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“…Despite some progress in studying the possibility of enhancing the antioxidant properties of albumin, the development of the methods for correcting oxidative stress taking into account this ability of the protein is still in its infancy. Recently, such classes of compounds as thiol antioxidants ( n -acetylcysteine, carbocysteine and erdosteine), superoxide dismutase mimetics (magnesium-containing porphyrins), NADPH oxidase inhibitors (apocinin, diphenyliod), setanaxib traps (disulfenton sodium), activators of the transcription factor Nrf2 (Sulforaphane, Bardoxelone methyl, Dimethylfumarate) have been actively tested or are already being used to reduce oxidative stress [ 168 , 169 , 170 , 171 ]. It might be that in the future it will be possible to create the complex therapy for oxidative stress management taking into account the functional properties of albumin.…”

Section: Antioxidant Properties Of Albumin: Practical Applicationmentioning

confidence: 99%

The Universal Soldier: Enzymatic and Non-Enzymatic Antioxidant Functions of Serum Albumin

et al. 2020

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As a carrier of many biologically active compounds, blood is exposed to oxidants to a greater extent than the intracellular environment. Serum albumin plays a key role in antioxidant defence under both normal and oxidative stress conditions. This review evaluates data published in the literature and from our own research on the mechanisms of the enzymatic and non-enzymatic activities of albumin that determine its participation in redox modulation of plasma and intercellular fluid. For the first time, the results of numerous clinical, biochemical, spectroscopic and computational experiments devoted to the study of allosteric modulation of the functional properties of the protein associated with its participation in antioxidant defence are analysed. It has been concluded that it is fundamentally possible to regulate the antioxidant properties of albumin with various ligands, and the binding and/or enzymatic features of the protein by changing its redox status. The perspectives for using the antioxidant properties of albumin in practice are discussed.

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“…FMD is believed to be mediated by NO [ 13 ]. We have recently reviewed the evidence for elevated oxidative stress in PAD, as well as the interplay between NO and oxidative stress [ 19 ]. High levels of ROS can lead to the rapid inactivation of NO to form peroxynitrite, thus reducing the amount of bioactive NO [ 20 ].…”

Section: Endothelial Dysfunctionmentioning

confidence: 99%

Oxidative Stress and Arterial Dysfunction in Peripheral Artery Disease

et al. 2018

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Peripheral artery disease (PAD) is an atherosclerotic disease characterized by a narrowing of the arteries in the lower extremities. Disease manifestations are the result of more than just reduced blood flow, and include endothelial dysfunction, arterial stiffness, and inflammation. Growing evidence suggests that these factors lead to functional impairment and decline in PAD patients. Oxidative stress also plays an important role in the disease, and a growing amount of data suggest a link between arterial dysfunction and oxidative stress. In this review, we present the current evidence for the involvement of endothelial dysfunction, arterial stiffness, and inflammation in the pathophysiology of PAD. We also discuss the links between these factors and oxidative stress, with a focus on nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2)-derived reactive oxygen species (ROS) and decreased nitric oxide (NO) bioavailability. Finally, the potential therapeutic role of NOX2 antioxidants for improving arterial function and functional status in PAD patients is explored.

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Oxidative stress and antioxidant treatment in patients with peripheral artery disease

Cited by 43 publications

References 108 publications

Critical Limb Ischaemia Exacerbates Mitochondrial Dysfunction in ApoE–/– Mice Compared with ApoE+/+ Mice, but N-acetyl Cysteine still Confers Protection

Critical Limb Ischaemia Exacerbates Mitochondrial Dysfunction in ApoE–/– Mice Compared with ApoE+/+ Mice, but N-acetyl Cysteine still Confers Protection

The Universal Soldier: Enzymatic and Non-Enzymatic Antioxidant Functions of Serum Albumin

Oxidative Stress and Arterial Dysfunction in Peripheral Artery Disease

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