Protective Effects of Aspirin from Cardiac Hypertrophy and Oxidative Stress in Cardiomyopathic Hamsters

Objective. To evaluate the capacity of chronic ASA therapy to prevent cardiac alterations and increased oxidative stress in cardiomyopathic hamsters.Methods and Results. Male Syrian cardiomyopathic and age-matched inbred control hamsters received ASA orally from the age of 60 days. Animals were sacrificed at the age of 150, 250, and 350 days to evaluate the time course of cardiac hypertrophy and cardiovascular tissue superoxide anion (O2-) production. At the age of 150 days, the ventricular weight over body weight ratio, resting heart rate, and cardiovascularO2-production were much higher in cardiomyopathic hamsters than those in control. At the age of 250 days, in addition to the continual deterioration of these parameters with age, the blood pressure started to fall and the signs of heart failure appeared. In these cardiomyopathic hamsters, chronic ASA treatment (a) completely prevented elevatedO2-production and the NAD(P)H oxidase activity, (b) significantly slowed down the development of the cardiac hypertrophy and fibrosis.Conclusions. Chronic ASA treatment significantly prevents the deterioration of cardiac function and structure as well as the increased oxidative stress in the cardiomyopathic hamster. Our findings suggest that ASA presents a therapeutic potential to prevent cardiac dysfunction.

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Effects of long-term anti-ischemic drug treatment on Na,K-ATPase isoforms in cardiomyopathic hamsters

Cellular and Molecular Biology ◽

10.14715/cmb/2021.67.2.11 ◽

2021 ◽

Vol 67 (2) ◽

pp. 76-82

Author(s):

Jean Michel Maixent ◽

Sandrine V. Pierre ◽

Stéphane Sadrin ◽

Régis Guieu ◽

Franck Paganelli

Keyword(s):

Cardiac Hypertrophy ◽

Early Stage ◽

Weight Ratio ◽

Body Weight Ratio ◽

Membrane Expression ◽

Syrian Golden Hamsters ◽

Selective Modulation ◽

Cardiomyopathic Hamsters ◽

Induced Changes

We investigated the effects of long-term anti-ischemic therapy with trimetazidine on Na,K-ATPase (NKA) activity and protein expression in cardiomyopathy. NKA isoforms in membrane fractions from cardiomyopathic hamsters of the BIO 14.6 strain were studied and compared with those from healthy Syrian golden hamsters (F1B). Trimetazidine was orally administered to a subset of cardiomyopathic hamsters in the early stage of active disease (30 days) until the congestive stage (350 days). In the congestive stage of cardiac failure, the cardiomyopathic hamsters displayed altered NKA activity (-55 % vs. F1B; p<0.01), which was related to a specific decrease in abundance of the membrane NKA ?1 isoform (-27 % vs. F1B). Trimetazidine partially prevented the cardiomyopathy-induced changes in NKA activity (+38 %) and ?1 membrane expression (+ 66 %) without inducing changes in the expression of the ?2 isoform or 1 isoform of NKA. Cardiac hypertrophy and remodeling were reduced after trimetazidine treatment. Additionally, the abundance of NKA ?1 in membranes was negatively correlated with the ventricular weight/body weight ratio (an index of cardiac hypertrophy) (r2 = 0.99; p<0.0015). These findings suggest that some of the cardioprotective effect of trimetazidine during long-term cardiomyopathy may be achieved via regulation of cardiac remodeling and selective modulation cardiac NKA isoforms.

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Protocatechuic acid attenuates isoproterenol-induced cardiac hypertrophy via downregulation of ROCK1–Sp1–PKCγ axis

Scientific Reports ◽

10.1038/s41598-021-96761-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Liyan Bai ◽

Hae Jin Kee ◽

Xiongyi Han ◽

Tingwei Zhao ◽

Seung-Jung Kee ◽

...

Keyword(s):

Cardiac Hypertrophy ◽

Acid Treatment ◽

Protocatechuic Acid ◽

Therapeutic Potential ◽

Weight Ratio ◽

Left Ventricular ◽

Heart Weight ◽

Transcriptional Level ◽

Cell Area ◽

Protective Effects

AbstractCardiac hypertrophy is an adaptive response of the myocardium to pressure overload or adrenergic agonists. Here, we investigated the protective effects and the regulatory mechanism of protocatechuic acid, a phenolic compound, using a mouse model of isoproterenol-induced cardiac hypertrophy. Our results demonstrated that protocatechuic acid treatment significantly downregulated the expression of cardiac hypertrophic markers (Nppa, Nppb, and Myh7), cardiomyocyte size, heart weight to body weight ratio, cross-sectional area, and thickness of left ventricular septum and posterior wall. This treatment also reduced the expression of isoproterenol-induced ROCK1, Sp1, and PKCγ both in vivo and in vitro. To investigate the mechanism, we performed knockdown and overexpression experiments. The knockdown of ROCK1, Sp1, or PKCγ decreased the isoproterenol-induced cell area and the expression of hypertrophic markers, while the overexpression of Sp1 or PKCγ increased the levels of hypertrophic markers. Protocatechuic acid treatment reversed these effects. Interestingly, the overexpression of Sp1 increased cell area and induced PKCγ expression. Furthermore, experiments using transcription inhibitor actinomycin D showed that ROCK1 and Sp1 suppression by protocatechuic acid was not regulated at the transcriptional level. Our results indicate that protocatechuic acid acts via the ROCK1/Sp1/PKCγ axis and therefore has promising therapeutic potential as a treatment for cardiac hypertrophy.

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Histone Deacetylase Inhibition has Cardiac and Vascular Protective Effects in Rats With Pressure Overload Cardiac Hypertrophy

Physiological Research ◽

10.33549/physiolres.934110 ◽

2019 ◽

pp. 727-737 ◽

Cited By ~ 6

Author(s):

H. JUNG ◽

E. LEE ◽

I. KIM ◽

J. SONG ◽

G. KIM

Keyword(s):

Oxidative Stress ◽

Cardiac Hypertrophy ◽

Histone Deacetylase ◽

Hdac Inhibitors ◽

Pressure Overload ◽

Aortic Ring ◽

Ascending Aorta ◽

Protective Effects ◽

Histone Deacetylase Inhibition ◽

And Oxidative Stress

Histone deacetylase (HDAC) inhibitors have shown beneficial effects in animal models of cardiovascular diseases. We hypothesized that HDAC inhibitor, sodium valproate (VPA), has cardiac and vascular protective effects in rats with pressure overload cardiac hypertrophy induced by transverse aortic constriction (TAC). Sections of the heart were visualized after hematoxylin and eosin staining, picrosirius red staining and immunohistochemistry. The expression of genes related to cardiac hypertrophy, fibrosis, and oxidative stress was determined by quantitative real-time polymerase chain reaction. The aortic ring tension analysis was conducted using both the ascending aorta and descending thoracic aorta. TAC increased the expression of hypertrophic, fibrotic, and oxidative stress genes, which was attenuated by VPA. In the ascending aorta with intact endothelium, there was a significant decrease in the relaxation response, which was recovered by VPA treatment. These results indicate that VPA has cardiac and vascular protective effects in rats with pressure overload cardiac hypertrophy.

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Effects of Montmorillonite on Growth Performance, Serum Biochemistry and Oxidative Stress of Red-Crowned Crane (Grus japonensis) Fed Mycotoxin-Contaminated Feed

Current Drug Metabolism ◽

10.2174/1389200221666200726221126 ◽

2020 ◽

Vol 21 (8) ◽

pp. 626-632 ◽

Cited By ~ 1

Author(s):

Dawei Liu ◽

Qinghua Wu ◽

Hongyi Liu ◽

Changhu Lu ◽

Chao Gu ◽

...

Keyword(s):

Oxidative Stress ◽

Growth Performance ◽

Feed Intake ◽

Animal Feed ◽

Bird Species ◽

Serum Biochemistry ◽

Protective Effects ◽

Regular Diet ◽

Grus Japonensis ◽

And Oxidative Stress

Background: The red-crowned crane (Grus japonensis) is one of the most vulnerable bird species in the world. Mycotoxins are toxic secondary metabolites produced by fungi and considered naturally unavoidable contaminants in animal feed. Our recent survey indicated that the mycotoxins had the potential to contaminate redcrowned crane’s regular diets in China. Objective: This experiment was conducted to investigate the protective effects of mycotoxin binder montmorillonite (Mont) on growth performance, serum biochemistry and oxidative stress parameters of the red-crowned crane. Methods: 16 red-crowned cranes were divided into four groups and fed one of the following diets; a selected diet, regular diet, or the selected diet or regular diet with 0.5% montmorillonite added to the diets. The cranes' parameters of performance, hematology, serum biochemistry and serum oxidative stress were measured. Results: Consuming regular diets decreased the average daily feed intake (ADFI), levels of haemoglobin (Hb), platelet count (PLT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), but increased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK) and lactate dehydrogenase (LDH). The supplementation of 0.5% Mont provided protection for the red-crowned crane in terms of feed intake, serum biochemistry and oxidative stress. Moreover, Mont supplementation had no adverse effect on the health of red-crowned crane. Conclusions: Taken together, these findings suggested that the addition of dietary Mont is effective in improving the health of red-crowned crane.

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Creatine Alleviates Doxorubicin-Induced Liver Damage by Inhibiting Liver Fibrosis, Inflammation, Oxidative Stress, and Cellular Senescence

Nutrients ◽

10.3390/nu13010041 ◽

2020 ◽

Vol 13 (1) ◽

pp. 41

Author(s):

Nouf Aljobaily ◽

Michael J. Viereckl ◽

David S. Hydock ◽

Hend Aljobaily ◽

Tsung-Yen Wu ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Methylation ◽

Body Weight ◽

Liver Fibrosis ◽

Liver Damage ◽

Cellular Senescence ◽

Weight Ratio ◽

Mrna Levels ◽

Body Weight Ratio ◽

Chromosomal Stability

Background: Treatment with the chemotherapy drug doxorubicin (DOX) may lead to toxicities that affect non-cancer cells including the liver. Supplementing the diet with creatine (Cr) has been suggested as a potential intervention to minimize DOX-induced side effects, but its effect in alleviating DOX-induced hepatoxicity is currently unknown. Therefore, we aimed to examine the effects of Cr supplementation on DOX-induced liver damage. Methods: Male Sprague-Dawley rats were fed a diet supplemented with 2% Cr for four weeks, 4% Cr for one week followed by 2% Cr for three more weeks, or control diet for four weeks. Animals then received either a bolus i.p. injection of DOX (15 mg/kg) or saline as a placebo. Animals were then sacrificed five days-post injection and markers of hepatoxicity were analyzed using the liver-to-body weight ratio, aspartate transaminase (AST)-to- alanine aminotransferase (ALT) ratio, alkaline phosphatase (ALP), lipemia, and T-Bilirubin. In addition, hematoxylin and eosin (H&E) staining, Picro-Sirius Red staining, and immunofluorescence staining for CD45, 8-OHdG, and β-galactosidase were performed to evaluate liver morphology, fibrosis, inflammation, oxidative stress, and cellular senescence, respectively. The mRNA levels for biomarkers of liver fibrosis, inflammation, oxidative stress, and senescence-related genes were measured in liver tissues. Chromosomal stability was evaluated using global DNA methylation ELISA. Results: The ALT/AST ratio and liver to body weight ratio tended to increase in the DOX group, and Cr supplementation tended to attenuate this increase. Furthermore, elevated levels of liver fibrosis, inflammation, oxidative stress, and senescence were observed with DOX treatment, and Cr supplementation prior to DOX treatment ameliorated this hepatoxicity. Moreover, DOX treatment resulted in chromosomal instability (i.e., altered DNA methylation profile), and Cr supplementation showed a tendency to restore chromosomal stability with DOX treatment. Conclusion: The data suggest that Cr protected against DOX-induced hepatotoxicity by attenuating fibrosis, inflammation, oxidative stress, and senescence.

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Fucoxanthin Ameliorates Oxidative Stress and Airway Inflammation in Tracheal Epithelial Cells and Asthmatic Mice

Cells ◽

10.3390/cells10061311 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1311

Author(s):

Shu-Ju Wu ◽

Chian-Jiun Liou ◽

Ya-Ling Chen ◽

Shu-Chen Cheng ◽

Wen-Chung Huang

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Airway Inflammation ◽

Inflammatory Cytokines ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Eosinophil Infiltration ◽

Tracheal Epithelial Cells ◽

Tracheal Epithelial ◽

And Oxidative Stress

Fucoxanthin is isolated from brown algae and was previously reported to have multiple pharmacological effects, including anti-tumor and anti-obesity effects in mice. Fucoxanthin also decreases the levels of inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of asthmatic mice. The purpose of the present study was to investigate the effects of fucoxanthin on the oxidative and inflammatory responses in inflammatory human tracheal epithelial BEAS-2B cells and attenuated airway hyperresponsiveness (AHR), airway inflammation, and oxidative stress in asthmatic mice. Fucoxanthin significantly decreased monocyte cell adherence to BEAS-2B cells. In addition, fucoxanthin inhibited the production of pro-inflammatory cytokines, eotaxin, and reactive oxygen species in BEAS-2B cells. Ovalbumin (OVA)-sensitized mice were treated by intraperitoneal injections of fucoxanthin (10 mg/kg or 30 mg/kg), which significantly alleviated AHR, goblet cell hyperplasia and eosinophil infiltration in the lungs, and decreased Th2 cytokine production in the BALF. Furthermore, fucoxanthin significantly increased glutathione and superoxide dismutase levels and reduced malondialdehyde (MDA) levels in the lungs of asthmatic mice. These data demonstrate that fucoxanthin attenuates inflammation and oxidative stress in inflammatory tracheal epithelial cells and improves the pathological changes related to asthma in mice. Thus, fucoxanthin has therapeutic potential for improving asthma.

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Coptisine Attenuates Diabetes—Associated Endothelial Dysfunction through Inhibition of Endoplasmic Reticulum Stress and Oxidative Stress

Molecules ◽

10.3390/molecules26144210 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4210

Author(s):

Yan Zhou ◽

Chunxiu Zhou ◽

Xutao Zhang ◽

Chi Teng Vong ◽

Yitao Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Risk Factors ◽

Endoplasmic Reticulum ◽

Er Stress ◽

Vascular Function ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Ex Vivo ◽

Diabetic Mice ◽

And Oxidative Stress

Coptisine is the major bioactive protoberberine alkaloid found in Rhizoma Coptidis. Coptisine reduces inflammatory responses and improves glucose tolerance; nevertheless, whether coptisine has vasoprotective effect in diabetes is not fully characterized. Conduit arteries including aortas and carotid arteries were obtained from male C57BL/6J mice for ex vivo treatment with risk factors (high glucose or tunicamycin) and coptisine. Some arterial rings were obtained from diabetic mice, which were induced by high-fat diet (45% kcal% fat) feeding for 6 weeks combined with a low-dose intraperitoneal injection of streptozotocin (120 mg/kg). Functional studies showed that coptisine protected endothelium-dependent relaxation in aortas against risk factors and from diabetic mice. Coptisine increased phosphorylations of AMPK and eNOS and downregulated the endoplasmic reticulum (ER) stress markers as determined by Western blotting. Coptisine elevates NO bioavailability and decreases reactive oxygen species level. The results indicate that coptisine improves vascular function in diabetes through suppression of ER stress and oxidative stress, implying the therapeutic potential of coptisine to treat diabetic vasculopathy.

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