4-Hydroxy-2-nonenal: a critical target in oxidative stress?

Breitzig, Mason; Bhimineni, Charishma; Lockey, Richard F.; Kolliputi, Narasaiah

doi:10.1152/ajpcell.00101.2016

Cited by 172 publications

(124 citation statements)

References 47 publications

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“…This pathway can activate the synthesis of several substances such as: γ-glutamyl transferase, γ-glutamyl transpeptidase, HSP-70, HO-1, and antioxidant enzymes such as SOD, GPx, CAT and glucose-6-phosphate dehydrogenase [21]. In addition, these pluripotent effects of 4-HNE can be explained by its concentration-dependent interactions with the cytokine networks and complex cellular antioxidant systems also showing cell and tissue specificities [59,63].…”

Section: Ozone Therapy As Redox Modulatormentioning

confidence: 99%

Potential Cytoprotective Activity of Ozone Therapy in SARS-CoV-2/COVID-19

2020

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1) Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease in China at the end of 2019 has caused a large global outbreak. Systemic ozone therapy (OT) could be potentially useful in the clinical management of several complications secondary to SARS-CoV-2. The rationale and mechanism of action has already been proven clinically in other viral infections and has been shown in research studies to be highly effective at decreasing organ damage mediated by inflammation and oxidative stress. This review summarizes the OT studies that illustrate the possible cytoprotective mechanism of action of ozone and its physiological by-products in target organs affected by SARS-CoV-2. (2) Methods: This review encompasses a total of 74 peer-reviewed original articles. It is mainly focused on ozone as a modulator of the NF-κB/Nrf2 pathways and IL-6/IL-1β expression. (3) Results: In experimental models and the few existent clinical studies, homeostasis of the free radical and antioxidant balance by OT was associated with a modulation of NF-κB/Nrf2 balance and IL-6 and IL-1β expression. These molecular mechanisms support the cytoprotective effects of OT against tissue damage present in many inflammatory diseases, including viral infections. (4) Conclusions: The potential cytoprotective role of OT in the management of organ damage induced by COVID-19 merits further research. Controlled clinical trials are needed.

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Section: Ozone Therapy As Redox Modulatormentioning

confidence: 99%

Potential Cytoprotective Activity of Ozone Therapy in SARS-CoV-2/COVID-19

2020

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“…Previous studies suggested that positive selection has acted on ALDH2 in EAS because of acquired resistance against parasite infection related to large‐scale rice cultivation (Koganebuchi et al, ; Luo et al, ; Oota et al, ). ALDH2 may be involved in the metabolism of 4‐hydroxy‐2‐nonenal, a byproduct of lipid peroxidation (Breitzig, Bhimineni, Lockey, & Kolliputi, ). Therefore, it is possible that the decreased ALDH2 enzyme activity may be associated with the prevalence of complex disorders through accelerated aging phenotypes because of the increased susceptibility to oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Evolutionary history of disease‐susceptibility loci identified in longitudinal exome‐wide association studies

Yasukochi

Sakuma

Takeuchi

et al. 2019

Molec Gen & Gen Med

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Background Our longitudinal exome‐wide association studies previously detected various genetic determinants of complex disorders using ~26,000 single‐nucleotide polymorphisms (SNPs) that passed quality control and longitudinal medical examination data (mean follow‐up period, 5 years) in 4884–6022 Japanese subjects. We found that allele frequencies of several identified SNPs were remarkably different among four ethnic groups. Elucidating the evolutionary history of disease‐susceptibility loci may help us uncover the pathogenesis of the related complex disorders. Methods In the present study, we conducted evolutionary analyses such as extended haplotype homozygosity, focusing on genomic regions containing disease‐susceptibility loci and based on genotyping data of our previous studies and datasets from the 1000 Genomes Project. Results Our evolutionary analyses suggest that derived alleles of rs78338345 of GGA3, rs7656604 at 4q13.3, rs34902660 of SLC17A3, and six SNPs closely located at 12q24.1 associated with type 2 diabetes mellitus, obesity, dyslipidemia, and three complex disorders (hypertension, hyperuricemia, and dyslipidemia), respectively, rapidly expanded after the human dispersion from Africa (Out‐of‐Africa). Allele frequencies of GGA3 and six SNPs at 12q24.1 appeared to have remarkably changed in East Asians, whereas the derived alleles of rs34902660 of SLC17A3 and rs7656604 at 4q13.3 might have spread across Japanese and non‐Africans, respectively, although we cannot completely exclude the possibility that allele frequencies of disease‐associated loci may be affected by demographic events. Conclusion Our findings indicate that derived allele frequencies of nine disease‐associated SNPs (rs78338345 of GGA3, rs7656604 at 4q13.3, rs34902660 of SLC17A3, and six SNPs at 12q24.1) identified in the longitudinal exome‐wide association studies largely increased in non‐Africans after Out‐of‐Africa.

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“…In other words, the effect of 4-HNE on the cell may be damaging or protective, depending on its concentration, respectively, not only on its production but also on the clearance of this molecule [2]. This suggests that, in some diseases, HNE may act as a target for detection, early prevention, and even cessation of disease progression [27].…”

Section: Hne Reactivity and Metabolismmentioning

confidence: 99%

4-Hydroxynonenal (HNE) and hepatic injury related to chronic oxidative stress

Bekyarova

Tzaneva

Bratoeva

et al. 2019

Biotechnology & Biotechnological Equipment

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4-Hydroxynonenal (HNE), a major end-product of free-radical activated peroxidation of polyunsaturated fatty acids, has attracted great scientific interest. HNE is more stable than free radicals and can diffuse within the cell or leave it and react with targets far from the initial site. These reactive aldehyde species are considerably reactive, producing multiple intra-and inter-molecular covalent adducts with biomolecules such as proteins, DNA and phospholipids. HNE is the most intensively studied aldehyde in relation to its physiological and protective function as a signalling molecule that stimulates gene expression and cell survival, as well as for its pathophysiological role as a toxic messenger that can propagate and amplify oxidative injury and promote mitochondrial dysfunction and cell death. Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world associated with oxidative stress, mitochondrial dysfunction and hepatocellular apoptosis. In this review we focus our attention on the molecular mechanism of the signalling and regulatory action of HNE. The role of HNE as a potent mediator for progression of liver injury in NAFLD is also discussed.

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4-Hydroxy-2-nonenal: a critical target in oxidative stress?

Cited by 172 publications

References 47 publications

Potential Cytoprotective Activity of Ozone Therapy in SARS-CoV-2/COVID-19

Potential Cytoprotective Activity of Ozone Therapy in SARS-CoV-2/COVID-19

Evolutionary history of disease‐susceptibility loci identified in longitudinal exome‐wide association studies

4-Hydroxynonenal (HNE) and hepatic injury related to chronic oxidative stress

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