The Two Sides of Vitamin E Supplementation

Ochi, Hiroki; Takeda, Satoshi

doi:10.1159/000366419

Cited by 18 publications

(13 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The physiological role of these mechanisms, which have, erroneously, long been considered by many as being essentially pathological and deleterious as indicated by the associated term ‘stress’, is therefore absolutely essential. This has been further demonstrated by a series of interventional studies using various antioxidants for the primary or secondary prevention of various diseases including cardiovascular diseases, cancer, retinitis and neurodegenerative diseases as well as in ageing, which, at best, have been shown to have little or no beneficial effects, with several antioxidants prescribed at low doses and deleterious effects at higher doses (Bjelakovic, Nikolova & Gluud, ; Bjelakovic, Nikolova & Gluud, ; Ochi & Takeda, ; Paolini et al ., ; Vainio, ; Vrolijk et al ., ).…”

Section: Discussionmentioning

confidence: 99%

Biomarkers of oxidative and nitro‐oxidative stress: conventional and novel approaches

Gašparović

Žarković

et al. 2017

British J Pharmacology

View full text Add to dashboard Cite

The concept of oxidative stress (OS) that connects altered redox biology with various diseases was introduced 30 years ago and has generated intensive research over the past two decades. Whereas it is now commonly accepted that macromolecule oxidation in response to ROS is associated with a variety of pathologies, the emergence of NO as a key regulator of redox signalling has led to the discovery of the pathophysiological significance of reactive nitrogen species (RNS). RNS can elicit various modifications of macromolecules and lead to nitrative or nitro-OS. In order to investigate oxidative and nitro-OS in human and in live animal models, circulating biomarker assays have been developed. This article provides an overview of key biomarkers used to assess lipid peroxidation and NO/NO 2 signalling, thereby stressing the necessity to analyse several OS biomarkers in relation to the overall (aerobic) metabolism and health condition of patients. In addition, the potential interest of heart rate variability as the non-invasive integrative biomarker of OS is discussed. LINKED ARTICLESThis article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc Abbreviations 4-HNE, trans-4-hydroxy-2-nonenal; ACR, acrolein; ALE, advanced lipoxidation end-products; DNP, 2,4-dinitrophenylhydrazine; FRR, free radical reaction; HRV, heart rate variability; LO, lipid alkoxyl radical; LOO, lipid peroxyl radical; LOOH, lipid hydroperoxide; LPO, lipid peroxidation; MDA, malondialdehyde; NO + , nitrosonium ion; Nrf2, Nuclear factor (erythroid-derived 2)-like 2; OMP, oxidatively modified protein; OS, oxidative stress; PUFA, polyunsaturated fatty acids; RNS, reactive nitrogen species; TBARS, thiobarbituric acid reactive substances; UPR, unfolded protein response IntroductionOxidative stress (OS), which was first introduced as a concept in redox biology and medicine in 1985 by Helmut Sies and Enrique Cadenas (Cadenas and Sies, 1985;Sies and Cadenas, 1985), has gained increasing interest over the years to become a major field of investigation in chemistry, life sciences and medicine.This concept connects oxidative chemistry with biological stress responses. However, it has the disadvantage of concealing redox chemistry, which plays a key role in cell homeostasis and signalling and in physiology, which is, for a large part, dependent on both oxidation and reduction reactions (Frein et al., 2005). This complex field of biochemistry, which plays a key role in the regulation of a variety of enzymes involved in essential signalling pathways, is now referred to as 'redox signalling' (Ullrich and Kissner, 2006) (Figure 1 et al., 2015). This reaction gives rise to peroxynitrite (ONOO À ), which is a highly reactive nitrogen species (RNS), producing nitration and nitrosation of substrates, often proteins that play important pathophysiological roles (Ullrich and Kissner, 2006;Schulz et al., 2008;Bottari, 20...

show abstract

Section: Discussionmentioning

confidence: 99%

Biomarkers of oxidative and nitro‐oxidative stress: conventional and novel approaches

Gašparović

Žarković

et al. 2017

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Clearly, it would be important that administered carbonyl scavengers possess physicochemical properties allowing them to protect critical targets of the "toxicologically significant" variety than the abundant "cytosolic electrophile scrubber" category which likely sustain survivable damage ( Figure 2) [5]. Yet "hard" versus "soft" scavengers could conceivably 10 differ in the extent to which they protected these distinct protein targets. For example, since its direct reactivity with soft LDEs is strongly favoured in kinetic terms, a soft nucleophilic scavenger might fully scavenge all intracellular LDEs, thereby protecting abundant non-essential "soft" targets in cytosol as well as low abundance "hard" targets that are of high toxicological relevance.…”

Section: Subcellular Distribution Of Macromolecular Targetsmentioning

confidence: 99%

“…While many strategies have been explored, a common approach has involved administering smallmolecule antioxidants to suppress LDE production at its source by quenching radical-mediated peroxidation of polyunsaturated fatty acids (PUFAs). Unfortunately, many evaluations of such molecules within randomised clinical trials have either failed to demonstrate human efficacy or displayed evidence of increased mortality [8][9][10][11]. The poor clinical performance of antioxidants is partly attributable to their nonspecific suppression of the essential physiological roles played by reactive oxygen species, thereby eliciting unanticipated side-effects and tissue dysfunction [12,13].…”

Section: Introductionmentioning

confidence: 99%

Carbonyl scavengers as pharmacotherapies in degenerative disease: Hydralazine repurposing and challenges in clinical translation

Burcham

2018

Biochemical Pharmacology

View full text Add to dashboard Cite

During cellular metabolism, spontaneous oxidative damage to unsaturated lipids generates many electrophilic carbonyl compounds that readily attack cell macromolecules, forming adducts that are potential drivers of tissue dysfunction. Since such damage is heightened in many degenerative conditions, researchers have assessed the efficacy of nucleophilic carbonyl-trapping drugs in animal models of such disorders, anticipating that they will protect tissues by intercepting toxic lipid-derived electrophiles (LDEs) within cells. This Commentary explores recent animal evidence for carbonyl scavenger efficacy in two disparate yet significant conditions known to involve LDE production, namely spinal cord injury (SCI) and alcoholic liver disease (ALD). Primary emphasis is placed on studies that utilised hydralazine, a clinically-approved "broad-spectrum" scavenger known to trap multiple LDEs. In addition to reviewing recent studies of hydralazine efficacy in animal SCI and ALD models, the Commentary reviews new insights concerning novel lifespan- and healthspan-extending properties of hydralazine obtained during studies in model invertebrate organisms, since the mechanisms involved seem of likely benefit during the treatment of degenerative disease. Finally, noting that human translation of the histoprotective properties of hydralazine have been limited, the final section of the Commentary will address two obstacles that hamper clinical translation of LDE-trapping therapies while also suggesting potential strategies for overcoming these problems.

show abstract

“…a-Toc or vitamin E in general is one of the most controversially discussed vitamins, since many positive as well as neutral or even harmful effects have been observed in human and animal supplementation studies [40][41][42].…”

Section: Discussionmentioning

confidence: 99%

Quantification of age‐related changes of α‐tocopherol in lysosomal membranes in murine tissues and human fibroblasts

et al. 2016

View full text Add to dashboard Cite

Considering the biological function of α‐tocopherol (α‐Toc) as a potent protective factor against oxidative stress, this antioxidant is in the focus of aging research. To understand the role of α‐Toc during aging we investigated α‐Toc concentrations in young and aged primary human fibroblasts after supplementation with RRR‐α‐Toc. Additionally, α‐Toc contents were determined in brain, kidney, and liver tissue of 10 week‐, 18 month‐, and 24 month‐old mice, which were fed a standard diet containing 100 mg/kg dl‐α‐tocopheryl acetate. α‐Toc concentrations in isolated lysosomes and the expression of the α‐Toc transport proteins Niemann Pick C1 (NPC1), Niemann Pick C2 (NPC2), and lipoprotein lipase were also analyzed. Obtained data show a significant age‐related increase of α‐Toc in murine liver, kidney, and brain tissue as well as in human dermal fibroblasts. Also liver and kidney lysosomes are marked by elevated α‐Toc contents with aging. NPC1 and NPC2 protein amounts are significantly decreased in adult and aged murine kidney tissue. Also aged human dermal fibroblasts show decreased NPC1 amounts. Supplementation of young and aged fibroblasts led also to decreased NPC1 amounts, suggesting a direct role of this protein in α‐Toc distribution. Our results indicate an age‐dependent increase of α‐Toc in different murine tissues as well as in human fibroblasts. Furthermore saturation and intracellular distribution of α‐Toc seem to be strongly dependent on the availability of this vitamin as well as on the presence of the lysosomal protein NPC1. © 2016 BioFactors, 42(3):307–315, 2016

show abstract

The Two Sides of Vitamin E Supplementation

Cited by 18 publications

References 53 publications

Biomarkers of oxidative and nitro‐oxidative stress: conventional and novel approaches

Biomarkers of oxidative and nitro‐oxidative stress: conventional and novel approaches

Carbonyl scavengers as pharmacotherapies in degenerative disease: Hydralazine repurposing and challenges in clinical translation

Quantification of age‐related changes of α‐tocopherol in lysosomal membranes in murine tissues and human fibroblasts

Contact Info

Product

Resources

About