The Role of Nrf2 in D-Galactose-Induced Cardiac Aging in Mice: Involvement of Oxidative Stress

Gerontology ◽  
2020 ◽  
pp. 1-10
Author(s):  
Xilan Yang ◽  
Jian Jia ◽  
Ling Ding ◽  
Zhen Yu ◽  
Chen Qu
Keyword(s):  
Oxidative Stress ◽  
Developed Countries ◽  
Antioxidative Effect ◽  
Cardiac Aging ◽  
Detailed Mechanism ◽  
Candidate Drug ◽  
Nrf2 Activator ◽  
And Oxidative Stress ◽  
Aging Cell

<b><i>Introduction:</i></b> Cardiac aging is the major risk factor for advanced heart disease, which is the leading cause of death in developed countries, accounting for &#x3e;30% of deaths worldwide. <b><i>Objective:</i></b> To discover the detailed mechanism of cardiac aging and develop an effective therapeutic candidate drug to treat or delay cardiac aging. <b><i>Methods:</i></b> We used D-galactose to induce cardiac aging in Nrf2<sup>+/+</sup> and Nrf2<sup>–/–</sup> mice, and then treated these mice with vehicle or the Nrf2 activator, CDDO-imidazolide (CDDO-Im). <b><i>Results and Conclusions:</i></b> D-galactose injection significantly induced cardiac aging, cell apoptosis, and oxidative stress in Nrf2<sup>+/+</sup> mice, all of which were further exacerbated in Nrf2<sup>–/–</sup> mice. CDDO-Im treatment can effectively weaken oxidative stress and enhance the activities of antioxidant enzymes, but CDDO-Im lost its antioxidative effect in the Nrf2<sup>–/–</sup> mice. Nrf2 activator CDDO-Im could therefore effectively protect against D-galactose-induced cardiac aging by inhibiting oxidative stress, suggesting that CDDO-Im might be a potential and promising therapeutic candidate drug to treat cardiac aging.

Inhibition of microRNA-155 Alleviates Neurological Dysfunction Following Transient Global Ischemia and Contribution of Neuroinflammation and Oxidative Stress in the Hippocampus

2020 ◽  
Vol 25 (40) ◽  
pp. 4310-4317 ◽  
Author(s):  
Lichao Sun ◽  
Shouqin Ji ◽  
Jihong Xing
Keyword(s):  
Oxidative Stress ◽  
Brain Edema ◽  
Severity Score ◽  
Global Ischemia ◽  
Signal Pathways ◽  
Neurological Severity Score ◽  
Tnf Α ◽  
Transient Global Ischemia ◽  
And Oxidative Stress

Background/Aims: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine the role of microRNA- 155 (miR-155) in regulating IL-1β, IL-6 and TNF-α in the hippocampus of rats with induction of CA. We further examined the levels of products of oxidative stress 8-isoprostaglandin F2α (8-iso PGF2α, indication of oxidative stress); and 8-hydroxy-2’-deoxyguanosine (8-OHdG, indication of protein oxidation) after cerebral inhibition of miR-155. Methods: CA was induced by asphyxia and followed by cardiopulmonary resuscitation in rats. ELISA and western blot analysis were used to determine the levels of PICs and products of oxidative stress; and the protein expression of NADPH oxidase (NOXs) in the hippocampus. In addition, neurological severity score and brain edema were examined to assess neurological functions. Results: We observed amplification of IL-1β, IL-6 and TNF-α along with 8-iso PGF2α and 8-OHdG in the hippocampus of CA rats. Cerebral administration of miR-155 inhibitor diminished upregulation of PICs in the hippocampus. This also attenuated products of oxidative stress and upregulation of NOX4. Notably, inhibition of miR-155 improved neurological severity score and brain edema and this was linked to signal pathways of PIC and oxidative stress. Conclusion: We showed the significant role of blocking miR-155 signal in improving the neurological function in CA rats likely via inhibition of signal pathways of neuroinflammation and oxidative stress, suggesting that miR-155 may be a target in preventing and/or alleviating development of the impaired neurological functions during CA-evoked global cerebral ischemia.

LncRNA SNHG12 Improves Cerebral Ischemic-reperfusion Injury by Activating SIRT1/FOXO3a Pathway through I nhibition of Autophagy and Oxidative Stress

2020 ◽  
Vol 17 (4) ◽  
pp. 394-401
Author(s):  
Yuanhua Wu ◽  
Yuan Huang ◽  
Jing Cai ◽  
Donglan Zhang ◽  
Shixi Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Cell Activity ◽  
Ht22 Cells ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Reperfusion ◽  
And Oxidative Stress

Background: Ischemia/reperfusion (I/R) injury involves complex biological processes and molecular mechanisms such as autophagy. Oxidative stress plays a critical role in the pathogenesis of I/R injury. LncRNAs are the regulatory factor of cerebral I/R injury. Methods: This study constructs cerebral I/R model to investigate role of autophagy and oxidative stress in cerebral I/R injury and the underline regulatory mechanism of SIRT1/ FOXO3a pathway. In this study, lncRNA SNHG12 and FOXO3a expression was up-regulated and SIRT1 expression was down-regulated in HT22 cells of I/R model. Results: Overexpression of lncRNA SNHG12 significantly increased the cell viability and inhibited cerebral ischemicreperfusion injury induced by I/Rthrough inhibition of autophagy. In addition, the transfected p-SIRT1 significantly suppressed the release of LDH and SOD compared with cells co-transfected with SIRT1 and FOXO3a group and cells induced by I/R and transfected with p-SNHG12 group and overexpression of cells co-transfected with SIRT1 and FOXO3 further decreased the I/R induced release of ROS and MDA. Conclusion: In conclusion, lncRNA SNHG12 increased cell activity and inhibited oxidative stress through inhibition of SIRT1/FOXO3a signaling-mediated autophagy in HT22 cells of I/R model. This study might provide new potential therapeutic targets for further investigating the mechanisms in cerebral I/R injury and provide.

The Concomitance of Hypertension and Diabetes Exacerbating Retinopathy: The Role of Inflammation and Oxidative Stress.

2013 ◽  
Vol 8 (4) ◽  
pp. 266-277 ◽  
Author(s):  
Diego Duarte ◽  
Kamila Silva ◽  
Mariana Rosales ◽  
José Lopes de Faria ◽  
Jacqueline Lopes de Faria
Keyword(s):  
Oxidative Stress ◽  
And Oxidative Stress

scholarly journals Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 629
Author(s):  
Jorge Gutiérrez-Cuevas ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Hugo Christian Monroy-Ramírez ◽  
Marina Galicia-Moreno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Peroxisome Proliferator ◽  
White Adipocyte ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Oxidative Stress

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.

The aging-induced hyperexcretion of glucose-dependent insulinotropic peptide is essential for the healthy cardiac remodeling by prevention of cardiac ceramide accumulation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Kureishi Bando ◽  
Y.R Remina ◽  
T.K Kamihara ◽  
K.N Nishimura ◽  
T.M Murohara
Keyword(s):  
Oxidative Stress ◽  
Ketone Bodies ◽  
Left Ventricular ◽  
Heart Weight ◽  
Lv Function ◽  
Cardiac Aging ◽  
Normal Left Ventricular ◽  
Insulinotropic Peptide ◽  
Ceramide Accumulation ◽  
And Oxidative Stress

Abstract Background Glucose-dependent insulinotropic peptide (GIP) is incretin hormone that is emerged as an important regulator of lipid metabolism. Fat intake induces hypersecretion of GIP that is involved in obesity and ectopic fat accumulation. Aging is another stimulant of GIP hypersecretion, which is suggested as a cause of “sarcopenic obesity in elderly”. In heart, aging is the known risk factor of HFpEF, of which typical characteristics is pathological cardiac hypertrophy induced by unknown cause(s). It remained uncertain whether any ectopic fat accumulation, such as cardiac steatosis may cause the aging-induced cardiac hypertrophy. Ceramide is one of the lipid metabolites that involves in apoptosis, inflammation, and stress responses, which are among the pathogenic components of heart failure. However, it remained unclear whether the ceramide may play any pathophysiological role in cardiac aging. Purpose We thus hypothesized whether cardiac aging may alter cardiac lipid metabolism and the GIP may play a regulatory role in the cardiac aging via modulating cardiac steatosis, particularly ceramide. Methods Mouse model of GIPR deficiency (GIPR-KO) was employed and cardiac evaluation of GIPR-KO and the age-matched wild type mice were performed. Results Aging (50w/o) induced GIP hypersecretion in control mice and their body and heart weight were 50% increased as compared to younger counterpart (10w/o). In contrast, the aging-induced increase rate in body and heart weight of GIPR-KO was significantly lower (22%). Aging also increased the circulating ketone bodies with increase in FGF21 expression in heart and, notably, there was no pathological increase in cardiac ceremide and oxidative stress with normal left-ventricular (LV) function (LVEF=82.2±1.8). In contrast, GIPR-KO exhibited pathological increase in cardiac ceramide without the elevation of the circulating ketone bodies. The younger GIPR-KO (10 w/o) exhibited normal left-ventricular (LV) function, however, the older mice (50 w/o) exhibited systolic LV dysfunction (LVEF=55.8±8.5) with increase in cardiac apoptosis and oxidative stress. Cardiac ceramide accumulation was increased in the aged normal mice, which was significantly higher in the aged GIPR-KO. Furthermore, GIPR-KO exhibited increase in cardiac fibrosis and oxidative stress, which were absent in the aged normal counterpart. Conclusion Aging increased circulating GIP level the leads to compensatory rise in the circulating ketone bodies without pathological increase in cardiac ceremide and related oxidative stress in heart. Loss of GIP signaling caused pathological increase in cardiac ceramide, leading to the aging-induced progression of systolic left-ventricular dysfunction. Collectively, we conclude that the aging-induced GIP hyperexcretion is essential for the aging-induced healthy cardiac remodeling by augmenting compensatory ketone body elevation. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): KAKEN-HI

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 Gut microbiota accelerates cisplatin-induced acute liver injury associated with robust inflammation and oxidative stress in mice

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shenhai Gong ◽  
Yinglin Feng ◽  
Yunong Zeng ◽  
Huanrui Zhang ◽  
Meiping Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
16S Rrna ◽  
Gut Microbiota ◽  
Gene Sequencing ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Metabolomic Analysis ◽  
Rrna Gene Sequencing ◽  
And Oxidative Stress

Abstract Background Gut microbiota has been reported to be disrupted by cisplatin, as well as to modulate chemotherapy toxicity. However, the precise role of intestinal microbiota in the pathogenesis of cisplatin hepatotoxicity remains unknown. Methods We compared the composition and function of gut microbiota between mice treated with and without cisplatin using 16S rRNA gene sequencing and via metabolomic analysis. For understanding the causative relationship between gut dysbiosis and cisplatin hepatotoxicity, antibiotics were administered to deplete gut microbiota and faecal microbiota transplantation (FMT) was performed before cisplatin treatment. Results 16S rRNA gene sequencing and metabolomic analysis showed that cisplatin administration caused gut microbiota dysbiosis in mice. Gut microbiota ablation by antibiotic exposure protected against the hepatotoxicity induced by cisplatin. Interestingly, mice treated with antibiotics dampened the mitogen-activated protein kinase pathway activation and promoted nuclear factor erythroid 2-related factor 2 nuclear translocation, resulting in decreased levels of both inflammation and oxidative stress in the liver. FMT also confirmed the role of microbiota in individual susceptibility to cisplatin-induced hepatotoxicity. Conclusions This study elucidated the mechanism by which gut microbiota mediates cisplatin hepatotoxicity through enhanced inflammatory response and oxidative stress. This knowledge may help develop novel therapeutic approaches that involve targeting the composition and metabolites of microbiota.

Systemic inflammation and oxidative stress induced by inhaled paraquat in rat improved by carvacrol, possible role of PPARγ receptors

BioFactors ◽  
2021 ◽  
Author(s):  
Fatemeh Amin ◽  
Arghavan Memarzia ◽  
Hamideh Kazemi Rad ◽  
Farzaneh Shakeri ◽  
Mohammad Hossein Boskabady
Keyword(s):  
Oxidative Stress ◽  
Systemic Inflammation ◽  
And Oxidative Stress

Protective role of Sterculia tragacantha aqueous extract on pancreatic gene expression and oxidative stress parameters in streptozotocin-induced diabetic rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Basiru Olaitan Ajiboye ◽  
Babatunji Emmanuel Oyinloye ◽  
Jennifer Chidera Awurum ◽  
Sunday Amos Onikanni ◽  
Adedotun Adefolalu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Protective Role ◽  
Diabetic Rats ◽  
Gene Expressions ◽  
Ki 67 ◽  
Oxidative Stress Parameters ◽  
And Oxidative Stress ◽  
Stress Parameters

Abstract Objectives The current study evaluates the protective role of aqueous extract of Sterculia tragacantha leaf (AESTL) on pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67 and GLP-1R) and oxidative stress parameters in streptozotocin-induced diabetic rats. Methods Diabetes mellitus was induced into the experimental Wistar animals via intraperitoneal (IP) injection of streptozotocin (35 mg/kg body weight) and 5% glucose water was given to the rats for 24 h after induction. The animals were categorized into five groups of 10 rats each as follows normal control, diabetic control, diabetic rats administered AESTL (150 and 300 mg/kg body weight) and diabetic rats administered metformin (200 mg/kg) orally for two weeks. Thereafter, the animals were euthanized, blood sample collected, pancreas harvested and some pancreatic gene expressions (such as insulin, PCNA, PDX-1, KI-67, and GLP-1R)s as well as oxidative stress parameters were analyzed. Results The results revealed that AESTL significantly (p<0.05) reduced fasting blood glucose level, food and water intake, and lipid peroxidation in diabetic rats. Diabetic rats administered different doses of AESTL showed a substantial upsurge in body weight, antioxidant enzyme activities, and pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67, and GLP-1R). Conclusions It can therefore be concluded that AESTL has the ability to protect the pancreas during diabetes mellitus conditions.

scholarly journals Amino Acid Transporter LAT1 (SLC7A5) Mediates MeHg-Induced Oxidative Stress Defense in the Human Placental Cell Line HTR-8/SVneo

2021 ◽  
Vol 22 (4) ◽  
pp. 1707
Author(s):  
Sebastian Granitzer ◽  
Raimund Widhalm ◽  
Martin Forsthuber ◽  
Isabella Ellinger ◽  
Gernot Desoye ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amino Acid ◽  
De Novo ◽  
Structural Similarity ◽  
Amino Acid Transporter ◽  
Cell Number ◽  
Mehg Exposure ◽  
Acid Transporter ◽  
And Oxidative Stress

The placental barrier can protect the fetus from contact with harmful substances. The potent neurotoxin methylmercury (MeHg), however, is very efficiently transported across the placenta. Our previous data suggested that L-type amino acid transporter (LAT)1 is involved in placental MeHg uptake, accepting MeHg-L-cysteine conjugates as substrate due to structural similarity to methionine. The aim of the present study was to investigate the antioxidant defense of placental cells to MeHg exposure and the role of LAT1 in this response. When trophoblast-derived HTR-8/SVneo cells were LAT1 depleted by siRNA-mediated knockdown, they accumulated less MeHg. However, they were more susceptible to MeHg-induced toxicity. This was evidenced in decreased cell viability at a usually noncytotoxic concentration of 0.03 µM MeHg (~6 µg/L). Treatment with ≥0.3 µM MeHg increased cytotoxicity, apoptosis rate, and oxidative stress of HTR-8/SVneo cells. These effects were enhanced under LAT1 knockdown. Reduced cell number was seen when MeHg-exposed cells were cultured in medium low in cysteine, a constituent of the tripeptide glutathione (GSH). Because LAT1-deficient HTR-8/SVneo cells have lower GSH levels than control cells (independent of MeHg treatment), we conclude that LAT1 is essential for de novo synthesis of GSH, required to counteract oxidative stress. Genetic predisposition to decreased LAT1 function combined with MeHg exposure could increase the risk of placental damage.

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