scholarly journals Melatonin Modulation of Sirtuin-1 Attenuates Liver Injury in a Hypercholesterolemic Mouse Model

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Francesca Bonomini ◽  
Gaia Favero ◽  
Luigi Fabrizio Rodella ◽  
Mohammed H. Moghadasian ◽  
Rita Rezzani
Keyword(s):  
Oxidative Stress ◽  
Biochemical Markers ◽  
Antioxidant Properties ◽  
Sirtuin 1 ◽  
Oral Supplementation ◽  
Stress Markers ◽  
Serum Biochemical ◽  
Stress Signals

Hypercholesterolemia increases and exacerbates stress signals leading also to liver damage (LD) and failure. Sirtuin1 (SIRT1) is involved in lifespan extension and it plays an essential role in hepatic lipid metabolism. However, its involvement in liver hypercholesterolemic damage is not yet completely defined. This in vivo study evaluated the role of SIRT1 in the hypercholesterolemic-related LD and, then, investigated how oral supplementation of melatonin, pleiotropic indoleamine, may be protective. Control mice and apolipoprotein E-deficient mice (ApoE−/−) of 6 and 15 weeks of age were treated or not treated with melatonin at the dose of 10 mg/kg/day for 9 weeks. In this study, we evaluated serum biochemical markers, liver SIRT1 expression, and oxidative stress markers. We observed that hypercholesterolemia increased significantly serum cholesterol and triglycerides, reduced significantly liver SIRT1, and, in turn, induced hepatic oxidative stress in untreated ApoE−/− mice with respect to control mice. Interestingly, melatonin treatment improved serum biochemical markers and hepatic morphological impairment and inhibited oxidative stress through its antioxidant properties and also by SIRT1 upregulation. In summary, melatonin oral supplementation may represent a new protective approach to block hypercholesterolemic liver alterations involving also a SIRT1-dependent mechanism.

scholarly journals Oxidative stress promotes liver cancer metastasis via a PKA-activated RNF25/ECAD/YAP circuit

2022 ◽  
Author(s):  
Zhao Huang ◽  
Li Zhou ◽  
Jiufei Duan ◽  
Siyuan Qin ◽  
Yu Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cancer Metastasis ◽  
Anoikis Resistance ◽  
Antioxidant Genes ◽  
Redox Sensor ◽  
Stress Signals ◽  
Hcc Cells

Abstract Loss of E-cadherin (ECAD), often caused by epigenetic inactivation, is closely associated with tumor metastasis. However, how ECAD is regulated in response to oxidative stress during tumorigenesis is largely unknown. Here we identify RNF25 as a new E3 ligase of ECAD, whose activation by oxidative stress leads to ECAD protein degradation in hepatocellular carcinoma (HCC). Loss of ECAD activates YAP, which in turn promotes the transcription of RNF25, thus forming a positive feedback loop to sustain the ECAD downregulation. YAP activation mitigates oxidative stress in detached HCC cells by upregulating antioxidant genes, protecting detached HCC cells from ferroptosis, resulting in anoikis resistance. Mechanistically, we found that protein kinase A (PKA) senses oxidative stress by redox modification in its β catalytic subunit (PRKACB) at Cys200 and Cys344, which increases its kinase activity towards RNF25 phosphorylation at Ser450, facilitating RNF25-mediated degradation of ECAD. Moreover, RNF25 expression is associated with HCC metastasis and depletion of RNF25 is sufficient to diminish HCC invasion and metastasis in vitro and in vivo. Together, these results identify a dual role of RNF25 as a critical regulator of ECAD protein turnover, promoting both anoikis resistance and metastasis, and PKA is a necessary redox sensor to enable this process. Our study provides mechanistic insight into how tumor cells sense oxidative stress signals to spread while escaping cell death.

scholarly journals Berries and oxidative stress markers: an overview of human intervention studies

2015 ◽  
Vol 6 (9) ◽  
pp. 2890-2917 ◽  
Author(s):  
Cristian Del Bo’ ◽  
Daniela Martini ◽  
Marisa Porrini ◽  
Dorothy Klimis-Zacas ◽  
Patrizia Riso
Keyword(s):  
Oxidative Stress ◽  
Intervention Studies ◽  
Human Intervention ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Intervention Trials ◽  
And Oxidative Stress

Severalin vitroandin vivostudies have demonstrated that polyphenol-rich berries may counteract oxidative stress. In this review, we summarized the main finding from human intervention trials on the role of berries in the modulation of markers of oxidative lipid, protein and DNA damage.

scholarly journals Assessing the influence of curcumin in sex-specific oxidative stress, survival and behavior in Drosophila melanogaster

2020 ◽  
Vol 223 (22) ◽  
pp. jeb223867
Author(s):  
Abigail R. Esquivel ◽  
Jenna C. Douglas ◽  
Rachel M. Loughran ◽  
Thomas E. Rezendes ◽  
Kaela R. Reed ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Properties ◽  
Yellow Pigment ◽  
Specific Effects ◽  
Age Related ◽  
Stress Survival ◽  
Endogenous Antioxidant ◽  
And Behavior

ABSTRACTOxidative stress, which occurs from an imbalance of reactive oxygen and nitrogen species (RONS) and both endogenous and exogenous antioxidants, promotes aging and underlies sex-specific differences in longevity and susceptibility to age-related neurodegeneration. Recent evidence suggests that curcumin, a yellow pigment derived from turmeric and shown to exhibit antioxidant properties as a RONS scavenger, influences the regulation of genetic elements in endogenous antioxidant pathways. To investigate the role of curcumin in sex-specific in vivo responses to oxidative stress, Drosophila were reared on media supplemented with 0.25, 2.5 or 25 mmol l−1 curcuminoids (consisting of curcumin, demethoxycurcumin and bisdemethoxycurcumin) and resistance to oxidative stress and neural parameters were assessed. High levels of curcuminoids exhibited two sex-specific effects: protection from hydrogen peroxide as an oxidative stressor and alterations in turning rate in an open field. Taken together, these results suggest that the influence of curcuminoids as antioxidants probably relies on changes in gene expression and that sexual dimorphism exists in the in vivo response to curcuminoids.

scholarly journals The Role of the Oxidative Stress Markers in Endotelial Dysfunction at Cardiovascular Disease Patients

2020 ◽  
Vol 71 (1) ◽  
pp. 283-287
Author(s):  
Germaine Savoiu-Balint ◽  
Claudia Borza ◽  
Emeric Toth ◽  
Mihaiela Andoni ◽  
Ioan Demeter ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Endothelial Dysfunction ◽  
Antioxidant Properties ◽  
Oxidative Stress Markers ◽  
Direct Study ◽  
Stress Markers

Although oxidative stress itself is directly associated with the occurrence of atherosclerosis, and together with endothelial dysfunction is a marker of atherosclerotic risk, none of these two markers were directly correlated with the presence of atherosclerosis. This study investigated the correlation between oxidative stress and endothelial dysfunction in people with cardiovascular disease. Furthermore, another objective of this paper is the direct study of the effect of a compound with antioxidant properties, selenium, on a model of endothelial dysfunction induced on human vascular fragments.

Cytoglobin, a novel globin, plays an antifibrotic role in the kidney

2010 ◽  
Vol 299 (5) ◽  
pp. F1120-F1133 ◽  
Author(s):  
Imari Mimura ◽  
Masaomi Nangaku ◽  
Hiroshi Nishi ◽  
Reiko Inagi ◽  
Tetsuhiro Tanaka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Kidney ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Protective Effects ◽  
Transgenic Rats ◽  
Cultured Fibroblasts

Cytoglobin (Cygb), a novel member of the globin superfamily, is expressed by fibroblasts in various organs. However, its function remains unknown. Because of its localization, we speculated that a biological role of Cygb may be related to fibrogenesis. To clarify the role of Cygb in kidney fibrosis, we employed the remnant kidney model in rats. Immunohistochemical analysis showed an increase in Cygb expression in parallel with disease progression. To investigate the functional consequence of Cygb upregulation, we established transgenic rats overexpressing rat Cygb. Overexpression of Cygb improved histological injury, preserved renal function, and ameliorated fibrosis, as estimated by the accumulation of collagen I and IV as well as Masson trichrome staining. These protective effects of Cygb were associated with a decrease in nitrotyrosine deposition in the kidney and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) excretion as a marker of oxidative stress. We also performed in vitro studies utilizing a rat kidney fibroblast cell line transiently overexpressing Cygb, an inducible kidney cell transfected with Cygb, and primary cultured fibroblasts isolated from the kidneys of the transgenic rats. These different experimental systems consistently showed that Cygb inhibited collagen synthesis. Furthermore, mutant disruption of heme in Cygb that impaired its antioxidant properties led to the loss of antifibrotic effects, suggesting that Cygb reduces fibrosis via a radical scavenging function. In conclusion, we showed that Cygb plays an important role in protection of the kidney against fibrosis via the amelioration of oxidative stress both in vitro and in vivo. Cygb might represent a good therapeutic target in chronic kidney disease.

Abstract P370: The Role Of PJ-34 In The Protection Of Burn-induced Cardiomyopathy

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Jake J Wen ◽  
Ravi Radhakrishnan ◽  
Keyan Mobli ◽  
Geetha L Radhakrishnan
Keyword(s):  
Oxidative Stress ◽  
Culture Medium ◽  
Burn Injury ◽  
Sirtuin 1 ◽  
Post Translational Modification ◽  
Post Injury ◽  
Parp 1

Burn injury results in adverse myocardial remodeling and heart failure through circulatingcatecholamines and androgen and cytokine cascades. The DNA binding protein PARP1(poly ADP ribose polymerase 1) catalyzes a post translational modification to generatePARylation proteins,which changes the normal function of the modified proteins. Bothof PARP-1 and SIRT1 (sirtuin1) are NAD + dependent. In this study, we propose that PJ34 (PARP-1 inhibitor) would protect the function of burn-remodeled cardiomyocytes.Commercial rats were obtained and were subject to 60% total surface body area (TSBA)scald burns by immersing the abdomen and back in boiling water. They were immediatelytreated with the PJ34 post injury. Separately, the cardiomyocytes (Ac16) were exposedto burn-serum replaced culture medium with or without treatment of lentivirus-PARP1 KOand/or SIRT-PGC-1α agonists in vitro . The in vivo experiments showed that burn-ratsexhibited cardiac hypertrophy, fibrosis and an increase in the inflammatory markers IL-1β, IFN-γ and TNFα. Burned rats had an increased oxidative stress, concomitant withelevated PARP-1 activity and reduced Sirtuin-1 (SIRT1) expression. PJ34 treatment ledto increased SIRT1 and Peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) levels and attenuated oxidative stress, inflammation, and fibrosis. In vitro tests demonstrated that the treatments of PJ34 and SIRT1-PGC-1α axis agonists incardiomyocytes exposed to burn-serum replaced culture medium led to a significantreduction in mit ROS and mitochondrial dysfunction. In Conclusion, PARP1 depletion byPJ34 in vivo and Letivirus-PARP1 KO Ac16 in vitro attenuated cardiomyopathic featuresin burn-rats through the activation of SIRT1 and its downstream antioxidant defensemechanisms. The results of this study suggest a pivotal role of PARP-1 inhibition intreating burn-induced cardiomyopathy. Keywords: Burn injury; PJ34; PARP1; Cardiomyocyte; Lentivirus.

scholarly journals Neuroprotective Metabolites of Hericium erinaceus Promote Neuro-Healthy Aging

2021 ◽  
Vol 22 (12) ◽  
pp. 6379
Author(s):  
Elisa Roda ◽  
Erica Cecilia Priori ◽  
Daniela Ratto ◽  
Fabrizio De Luca ◽  
Carmine Di Iorio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Healthy Aging ◽  
Molecular Layer ◽  
Dietary Supplementation ◽  
Purkinje Neurons ◽  
Geriatric Syndrome ◽  
Oral Supplementation ◽  
Erinacine A ◽  
And Oxidative Stress

Frailty is a geriatric syndrome associated with both locomotor and cognitive decline, typically linked to chronic systemic inflammation, i.e., inflammaging. In the current study, we investigated the effect of a two-month oral supplementation with standardized extracts of H. erinaceus, containing a known amount of Erinacine A, Hericenone C, Hericenone D, and L-ergothioneine, on locomotor frailty and cerebellum of aged mice. Locomotor performances were monitored comparing healthy aging and frail mice. Cerebellar volume and cytoarchitecture, together with inflammatory and oxidative stress pathways, were assessed focusing on senescent frail animals. H. erinaceus partially recovered the aged-related decline of locomotor performances. Histopathological analyses paralleled by immunocytochemical evaluation of specific molecules strengthened the neuroprotective role of H. erinaceus able to ameliorate cerebellar alterations, i.e., milder volume reduction, slighter molecular layer thickness decrease and minor percentage of shrunken Purkinje neurons, also diminishing inflammation and oxidative stress in frail mice while increasing a key longevity regulator and a neuroprotective molecule. Thus, our present findings demonstrated the efficacy of a non-pharmacological approach, based on the dietary supplementation using H. erinaceus extract, which represent a promising adjuvant therapy to be associated with conventional geriatric treatments.

scholarly journals Protective Role of Natural and Semi-Synthetic Tocopherols on TNFα-Induced ROS Production and ICAM-1 and Cl-2 Expression in HT29 Intestinal Epithelial Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 160
Author(s):  
Vladana Domazetovic ◽  
Irene Falsetti ◽  
Caterina Viglianisi ◽  
Kristian Vasa ◽  
Cinzia Aurilia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Properties ◽  
Intestinal Barrier ◽  
Protective Role ◽  
Intercellular Adhesion Molecule ◽  
Intestinal Epithelial ◽  
Intercellular Adhesion Molecule 1 ◽  
Beneficial Effects ◽  
Bowel Diseases

Vitamin E, a fat-soluble compound, possesses both antioxidant and non-antioxidant properties. In this study we evaluated, in intestinal HT29 cells, the role of natural tocopherols, α-Toc and δ-Toc, and two semi-synthetic derivatives, namely bis-δ-Toc sulfide (δ-Toc)2S and bis-δ-Toc disulfide (δ-Toc)2S2, on TNFα-induced oxidative stress, and intercellular adhesion molecule-1 (ICAM-1) and claudin-2 (Cl-2) expression. The role of tocopherols was compared to that of N-acetylcysteine (NAC), an antioxidant precursor of glutathione synthesis. The results show that all tocopherol containing derivatives used, prevented TNFα-induced oxidative stress and the increase of ICAM-1 and Cl-2 expression, and that (δ-Toc)2S and (δ-Toc)2S2 are more effective than δ-Toc and α-Toc. The beneficial effects demonstrated were due to tocopherol antioxidant properties, but suppression of TNFα-induced Cl-2 expression seems not only to be related with antioxidant ability. Indeed, while ICAM-1 expression is strongly related to the intracellular redox state, Cl-2 expression is TNFα-up-regulated by both redox and non-redox dependent mechanisms. Since ICAM-1 and Cl-2 increase intestinal bowel diseases, and cause excessive recruitment of immune cells and alteration of the intestinal barrier, natural and, above all, semi-synthetic tocopherols may have a potential role as a therapeutic support against intestinal chronic inflammation, in which TNFα represents an important proinflammatory mediator.

scholarly journals Nutraceutical Supplementation Ameliorates Visual Function, Retinal Degeneration, and Redox Status in rd10 Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1033
Author(s):  
Lorena Olivares-González ◽  
Sheyla Velasco ◽  
Isabel Campillo ◽  
David Salom ◽  
Emilio González-García ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Degeneration ◽  
Antioxidant Properties ◽  
Photoreceptor Cells ◽  
Redox Status ◽  
Inherited Retinal Dystrophies ◽  
Stress Markers ◽  
Retinal Dystrophies ◽  
Progressive Degeneration ◽  
Light Stimuli

Background: Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by progressive degeneration of photoreceptor cells. Ocular redox status is altered in RP suggesting oxidative stress could contribute to their progression. In this study, we investigated the effect of a mixture of nutraceuticals with antioxidant properties (NUT) on retinal degeneration in rd10 mice, a model of RP. Methods: NUT was orally administered to rd10 mice from postnatal day (PD) 9 to PD18. At PD18 retinal function and morphology were examined by electroretinography (ERG) and histology including TUNEL assay, immunolabeling of microglia, Müller cells, and poly ADP ribose polymers. Retinal redox status was determined by measuring the activity of antioxidant enzymes and some oxidative stress markers. Gene expression of the cytokines IL-6, TNFα, and IL-1β was assessed by real-time PCR. Results: NUT treatment delayed the loss of photoreceptors in rd10 mice partially preserving their electrical responses to light stimuli. Moreover, it ameliorated redox status and reduced inflammation including microglia activation, upregulation of cytokines, reactive gliosis, and PARP overactivation. Conclusions: NUT ameliorated retinal functionality and morphology at early stages of RP in rd10 mice. This formulation could be useful as a neuroprotective approach for patients with RP in the future.

scholarly journals Regulation of miRNAs by Natural Antioxidants in Cardiovascular Diseases: Focus on SIRT1 and eNOS

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 377
Author(s):  
Yunna Lee ◽  
Eunok Im
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Natural Antioxidants ◽  
Sirtuin 1 ◽  
Potential Benefits ◽  
New Perspective ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Cardiovascular diseases (CVDs) are the most common cause of morbidity and mortality worldwide. The potential benefits of natural antioxidants derived from supplemental nutrients against CVDs are well known. Remarkably, natural antioxidants exert cardioprotective effects by reducing oxidative stress, increasing vasodilation, and normalizing endothelial dysfunction. Recently, considerable evidence has highlighted an important role played by the synergistic interaction between endothelial nitric oxide synthase (eNOS) and sirtuin 1 (SIRT1) in the maintenance of endothelial function. To provide a new perspective on the role of natural antioxidants against CVDs, we focused on microRNAs (miRNAs), which are important posttranscriptional modulators in human diseases. Several miRNAs are regulated via the consumption of natural antioxidants and are related to the regulation of oxidative stress by targeting eNOS and/or SIRT1. In this review, we have discussed the specific molecular regulation of eNOS/SIRT1-related endothelial dysfunction and its contribution to CVD pathologies; furthermore, we selected nine different miRNAs that target the expression of eNOS and SIRT1 in CVDs. Additionally, we have summarized the alteration of miRNA expression and regulation of activities of miRNA through natural antioxidant consumption.

Sign in / Sign up

Export Citation Format

Share Document