Blueberry extract attenuates norepinephrine-induced oxidative stress and apoptosis in H9c2 cardiac cells

Abstract Aim of the study Sepsis has well-documented inflammatory effects on cardiovascular and blood cells. This study is designed to investigate potential anti-inflammatory effects of metformin on cardiac and blood cells 12 and 24 h following cecal ligation and puncture (CLP)-induced sepsis. Methods For the purpose of this study, 36 male Wistar rats were divided into six groups: two groups underwent CLP, two groups underwent CLP and received metformin, and two groups only received sham operations. 12 h later, 18 rats (half of rats in each of the three aforementioned groups) were sacrificed and cardiac and blood cells were harvested. Subsequently, 12 h later, the rest of the rats were euthanatized. In all harvested blood and cardiac cells, oxidative stress indicators, antioxidant properties, count of blood cells, neutrophil infiltration, percentage of weight loss and pathological assessment were conducted. Results In our experiment, metformin elevated antioxidant levels, improved function of blood cells and percentage of weight loss. Moreover, in the groups which received metformin, oxidative stress and neutrophil infiltration markers were decreased significantly. Moreover, pathological investigations of cardiac cell injury were reduced in the metformin group. Conclusions Our findings suggest that in CLP induced sepsis model, metformin can improve the function of blood and cardiac cells through alleviating inflammation, improvement of anti-inflammation properties, and enhancement of blood profile, and all these effects are more pronounced after 24 h in comparison with 12 h after induction of sepsis.

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CARDIOPROTECTIVE POTENTIAL OF QUERCETIN AGAINST DIESEL OR PETROL EXHAUST NANOPARTICLE INDUCED TOXICITY: A PROSPECTIVE IN VITRO PHARMACOLOGICAL STUDY IN H9C2 CELLS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2021.v14i4.40858 ◽

2021 ◽

pp. 139-144

Author(s):

MOHAN DURGA ◽

THIYAGARAJAN DEVASENA

Keyword(s):

Oxidative Stress ◽

Diesel Exhaust ◽

Pharmacological Study ◽

Lethal Effect ◽

Protective Role ◽

Cardiac Cells ◽

H9c2 Cells ◽

Sod Activity ◽

Cardioprotective Effects

Objective: Phytochemicals are known to elicit potential antioxidant activity. This study examined the cardioprotective effects of quercetin against oxidative damage to rat cardiomyocyte cells (H9c2) after treatment with Diesel Exhaust Nanoparticles (DEPs) or Petrol Exhaust Nanoparticles (PEPs). Methods: Cardiomyocyte cells were exposed to DEPs or PEPs alone and in a combination with quercetin for 24 h. Results: Results showed that quercetin had no lethal effect on H9c2 cells up to a concentration of 1.0 μg/ml. Exposure to DEPs (4.0 μg/ml) or PEPs (10.0 μg/ml) induced cytotoxicity, oxidative stress, and inflammation (p<0.05). It also provoked lipid peroxidation by an increase in MDA and a decrease in SOD activity and glutathione activity (p<0.05). Simultaneous addition of quercetin restored these parameters to near normal. Conclusion: These results thus specify that quercetin plays a protective role in cardiac cells exposed to DEPs and PEPs.

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H2S Protects against Cardiac Cell Hypertrophy through Regulation of Selenoproteins

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/6494306 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Adam Greasley ◽

Yanjie Zhang ◽

Bo Wu ◽

Yanxi Pei ◽

Nelson Belzile ◽

...

Keyword(s):

Oxidative Stress ◽

Cardiac Hypertrophy ◽

Critical Role ◽

Thioredoxin Reductase ◽

Cardiac Cells ◽

Keshan Disease ◽

Mouse Heart ◽

Cardiac Cell ◽

Cell Hypertrophy ◽

Expression Of Genes

Cardiac hypertrophy is defined as the enlargement of the cardiac myocytes, leading to improper nourishment and oxygen supply due to the increased functional demand. This increased stress on the cardiac system commonly leads to myocardial infarction, contributing to 85% of all cardiac-related deaths. Cystathionine gamma-lyase- (CSE-) derived H2S is a novel gasotransmitter and plays a critical role in the preservation of cardiac functions. Selenocysteine lyase (SCLY) has been identified to produce H2Se, the selenium homologue of H2S. Deficiency of selenium is often found in Keshan disease, a congestive cardiomyopathy. The interaction of H2S and H2Se in cardiac cell hypertrophy has not been explored. In this study, cell viability was evaluated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Oxidative stress and cell size were observed through immunostaining. The expression of genes was determined by real-time PCR and western blot. Here, we demonstrated that incubation of rat cardiac cells (H9C2) with H2O2 lead to increased oxidative stress and cell surface area, which were significantly attenuated by pretreatment of either H2S or H2Se. H2S incubation induced SCLY/H2Se signaling, which next caused higher expressions and activities of selenoproteins, including glutathione peroxidase and thioredoxin reductase. Furthermore, deficiency of CSE inhibited the expressions of SCLY and selenoprotein P in mouse heart tissues. We also found that both H2S and H2Se stimulated Nrf2-targeted downstream genes. These data suggests that H2S protects against cardiac hypertrophy through enhancement of a group of antioxidant proteins.

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Mitochondrial ATP-Sensitive Potassium Channels Inhibit Apoptosis Induced by Oxidative Stress in Cardiac Cells

Circulation Research ◽

10.1161/hh1201.092094 ◽

2001 ◽

Vol 88 (12) ◽

pp. 1267-1275 ◽

Cited By ~ 190

Author(s):

Masaharu Akao ◽

Andreas Ohler ◽

Brian O’Rourke ◽

Eduardo Marbán

Keyword(s):

Oxidative Stress ◽

Potassium Channels ◽

Cardiac Cells

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Effect of Quercetin and Intermittent and Continuous Exercise on Catalase, Superoxide dismutase, and Malondialdehyde in the Heart of Rats with Colon Cancer

Basic & Clinical Cancer Research ◽

10.18502/bccr.v12i1.5733 ◽

2021 ◽

Author(s):

Behrooz Talaei ◽

Mohammad Panji ◽

Fatemeh Nazari Robati ◽

Sajjad Tezerji

Keyword(s):

Oxidative Stress ◽

Colorectal Cancer ◽

Superoxide Dismutase ◽

Cardiac Tissue ◽

Intermittent Exercise ◽

Heart Tissue ◽

Cardiac Cells ◽

Heart Cells ◽

Oxidative Stress Biomarkers ◽

Continuous Exercise

Background: Colorectal cancer is the fourth leading cause of death globally, and the second most common cancer in Europe. About 8% of all cancer-related deaths occur due to colorectal cancer, and the highest prevalence has been reported in Asia and Eastern Europe. Methods: In this experimental study, 80 rats were divided into two groups of cases (n=70) and controls (n=10). Colorectal cancer was induced weekly in rats by subcutaneous injection of 15 mg/kg Azoxymethane. The rats were then divided into 7 experimental subgroups of patients, saline, quercetin, intermittent exercise, continuous exercise, quercetin plus intermittent, and quercetin plus continuous exercise. Oxidative stress biomarkers, including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were measured in the rats’ heart tissue by the ELISA method. Data were analyzed using ANOVA by SPSS software. Results: Oxidative stress in heart cells increased due to colorectal cancer. Quercetin alone or in combination with exercise significantly increased mean levels of CAT and SOD in the heart tissue of rats compared with patient and saline groups (P<0.0001). In contrast, the MDA level was significantly decreased (P<0.05). Conclusion: Colorectal cancer increased the oxidative stress in cardiac cells. Quercetin alone improved oxidative stress in cardiac tissue, and its combination with exercise was more effective.

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Bucindolol Modulates Cardiac Remodeling by Attenuating Oxidative Stress in H9c2 Cardiac Cells Exposed to Norepinephrine

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/6325424 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11

Author(s):

Bruna Gazzi de Lima-Seolin ◽

Ashley Nemec-Bakk ◽

Heidi Forsyth ◽

Stefanie Kirk ◽

Alex Sander da Rosa Araujo ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Signaling Pathways ◽

Cardiac Remodeling ◽

Cardiac Cells ◽

Antagonist Activity ◽

Pathological Hypertrophy ◽

Adrenergic Blocker ◽

Cell Death Signaling ◽

And Oxidative Stress

The increased circulation of norepinephrine, found in the diseased heart as a result of sympathetic nervous system overactivation, is responsible for its cardiotoxic effects including pathological hypertrophy, cell death, and oxidative stress. Bucindolol is a third generation adrenergic blocker, which acts on the β1 and β2 receptors, and has additional α1 antagonist activity. Thus, the aim of this study was to investigate the action of bucindolol on oxidative stress, hypertrophy, cell survival, and cell death signaling pathways in H9c2 cardiac cells exposed to norepinephrine. H9c2 cells were incubated with 10 μM norepinephrine for 24 h in the presence or absence of bucindolol (10 μM) treatment for 8 h. Western blot was used to determine the expression of proteins for hypertrophy/survival and death signaling pathways. Flow cytometry was used to assess cell death via caspase-3/7 activity and propidium iodide and reactive oxygen species via measuring the fluorescence of CM-H2DCFDA. Norepinephrine exposure resulted in an increase in oxidative stress as well as cell death. This was accompanied by an increased protein expression of LC3B-II/I. The protein kinase B/mammalian target of the rapamycin (Akt/mTOR) pathway which is involved in cardiac remodeling process was activated in response to norepinephrine and was mitigated by bucindolol. In conclusion, bucindolol was able to modulate cardiac remodeling which is mediated by oxidative stress.

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Abstract 217: Long Non-coding RNA Myocardial Infarction-associated Transcript (MIAT) Protects Cardiac Progenitor Cells From Oxidative Stress-induced Cell Death

Circulation Research ◽

10.1161/res.119.suppl_1.217 ◽

2016 ◽

Vol 119 (suppl_1) ◽

Author(s):

Liu Yang ◽

Yang Yu ◽

Baron Arnone ◽

Chan Boriboun ◽

Jiawei Shi ◽

...

Keyword(s):

Oxidative Stress ◽

Myocardial Infarction ◽

Cell Death ◽

Progenitor Cells ◽

Cardiac Cells ◽

Border Zone ◽

Mouse Heart ◽

Cardiac Progenitor Cells

Background: Long non-coding RNAs (lncRNAs) are an emerging class of RNAs with no or limited protein-coding capacity; a few of which have recently been shown to regulate critical biological processes. Myocardial infarction-associated transcript (MIAT) is a conserved mammalian lncRNA, and single nucleotide polymorphisms (SNPs) in 6 loci of this gene have been identified to be strongly associated with the incidence and severity of human myocardial infarction (MI). However, whether and how MIAT impacts on the pathogenesis of MI is unknown. Methods & Results: Quantitative RT-PCR analyses revealed that MIAT is expressed in neonatal mouse heart and to a lesser extent in adult heart. After surgical induction of MI in adult mice, MIAT starts to increase in 2 hours, peaks at 6 hours in atria and 12 hours in ventricles, and decreases to baseline at 24 hours. Fluorescent in situ hybridization (FISH) revealed a slight increase in the number of MIAT-expressing cells in the infarct border zone at 12 hours post-MI. Moreover, qRT-PCR analyses of isolated cardiac cells revealed that MIAT is predominantly expressed in cardiosphere-derived cardiac progenitor cells (CPCs). Treatment of CPCs with H 2 O 2 led to a marked upregulation of MIAT, while knockdown (KD) of MIAT resulted in a significantly impaired cell survival in vitro with H 2 O 2 treatment and in vivo after administered in the ischemic/reperfused heart. Notably, bioinformatics prediction and RNA immunoprecipitation identified FUS (fused in sarcoma) as a novel MIAT-interacting protein. FUS-KD CPCs displayed reduced cell viability and increased apoptosis under oxidative stress. Furthermore, MIAT overexpression enhanced survival of WT CPCs but not FUS-KD CPCs, suggesting that the protective role of MIAT is mediated by FUS. Conclusions: MIAT interacts with FUS to protect CPCs from oxidative stress-induced cell death.

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Modulation of potassium currents by angiotensin and oxidative stress in cardiac cells from the diabetic rat

The Journal of Physiology ◽

10.1113/jphysiol.2005.090639 ◽

2005 ◽

Vol 567 (1) ◽

pp. 177-190 ◽

Cited By ~ 26

Author(s):

Y. Shimoni ◽

D. Hunt ◽

M. Chuang ◽

K. Y. Chen ◽

G. Kargacin ◽

...

Keyword(s):

Oxidative Stress ◽

Potassium Currents ◽

Cardiac Cells ◽

Diabetic Rat ◽

And Oxidative Stress

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Lingonberry anthocyanins protect cardiac cells from oxidative-stress-induced apoptosis

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2016-0667 ◽

2017 ◽

Vol 95 (8) ◽

pp. 904-910 ◽

Cited By ~ 12

Author(s):

Cara K. Isaak ◽

Jay C. Petkau ◽

Heather Blewett ◽

Karmin O ◽

Yaw L. Siow

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Cardiac Cells ◽

Control Group ◽

Protective Effects ◽

H9c2 Cells ◽

Induced Apoptosis ◽

Hoechst Staining

Lingonberry grown in northern Manitoba, Canada, contains exceptionally high levels of anthocyanins and other polyphenols. Previous studies from our lab have shown that lingonberry anthocyanins can protect H9c2 cells from ischemia–reperfusion injury and anthocyanin-rich diets have been shown to be associated with decreased cardiovascular disease and mortality. Oxidative stress can impair function and trigger apoptosis in cardiomyocytes. This study investigated the protective effects of physiologically relevant doses of lingonberry extracts and pure anthocyanins against hydrogen-peroxide-induced cell death. Apoptosis and necrosis were detected in H9c2 cells after hydrogen peroxide treatment via flow cytometry using FLICA 660 caspase 3/7 combined with YO-PRO-1 and then confirmed with Hoechst staining and fluorescence microscopy. Each of the 3 major anthocyanins found in lingonberry (cyanidin-3-galactoside, cyanidin-3-glucoside, and cyanidin-3-arabinoside) was protective against hydrogen-peroxide-induced apoptosis in H9c2 cells at 10 ng·mL−1 (20 nmol·L−1) and restored the number of viable cells to match the control group. A combination of the 3 anthocyanins was also protective and a lingonberry extract tested at 3 concentrations produced a dose-dependent protective effect. Lingonberry anthocyanins protected cardiac cells from oxidative-stress-induced apoptosis and may have cardioprotective effects as a dietary modification.

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L-Carnitine: An Antioxidant Remedy for the Survival of Cardiomyocytes under Hyperglycemic Condition

Journal of Diabetes Research ◽

10.1155/2018/4028297 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

Fernanda Vacante ◽

Pamela Senesi ◽

Anna Montesano ◽

Alice Frigerio ◽

Livio Luzi ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

Signaling Pathways ◽

Stress Condition ◽

Cardiac Cells ◽

Ros Production ◽

Protective Effects ◽

H9c2 Cells ◽

Rat Cardiomyocytes ◽

Oxidative Stress Condition

Background. Metabolic alterations as hyperglycemia and inflammation induce myocardial molecular events enhancing oxidative stress and mitochondrial dysfunction. Those alterations are responsible for a progressive loss of cardiomyocytes, cardiac stem cells, and consequent cardiovascular complications. Currently, there are no effective pharmacological measures to protect the heart from these metabolic modifications, and the development of new therapeutic approaches, focused on improvement of the oxidative stress condition, is pivotal. The protective effects of levocarnitine (LC) in patients with ischemic heart disease are related to the attenuation of oxidative stress, but LC mechanisms have yet to be fully understood. Objective. The aim of this work was to investigate LC’s role in oxidative stress condition, on ROS production and mitochondrial detoxifying function in H9c2 rat cardiomyocytes during hyperglycemia. Methods. H9c2 cells in the hyperglycemic state (25 mmol/L glucose) were exposed to 0.5 or 5 mM LC for 48 and 72 h: LC effects on signaling pathways involved in oxidative stress condition were studied by Western blot and immunofluorescence analysis. To evaluate ROS production, H9c2 cells were exposed to H2O2 after LC pretreatment. Results. Our in vitro study indicates how LC supplementation might protect cardiomyocytes from oxidative stress-related damage, preventing ROS formation and activating antioxidant signaling pathways in hyperglycemic conditions. In particular, LC promotes STAT3 activation and significantly increases the expression of antioxidant protein SOD2. Hyperglycemic cardiac cells are characterized by impairment in mitochondrial dysfunction and the CaMKII signal: LC promotes CaMKII expression and activation and enhancement of AMPK protein synthesis. Our results suggest that LC might ameliorate metabolic aspects of hyperglycemic cardiac cells. Finally, LC doses herein used did not modify H9c2 growth rate and viability. Conclusions. Our novel study demonstrates that LC improves the microenvironment damaged by oxidative stress (induced by hyperglycemia), thus proposing this nutraceutical compound as an adjuvant in diabetic cardiac regenerative medicine.

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