ABSTRACT
Objectives Cardiac rehabilitation (CR) provides evidence-based secondary prevention for people with heart disease (HD) (clients). Despite HD being the leading cause of mortality and morbidity, CR is under-utilised in Australia. This research investigated healthcare systems required to improve access to CR in rural and remote areas of North Queensland (NQ). Methods A qualitatively dominant case study series to review management systems for CR in rural and remote areas of NQ was undertaken. Data collection was via semi-structured interviews in four tertiary hospitals and four rural or remote communities. An audit of discharge planning and CR referral, plus a review of community-based health services, was completed. An iterative and co-design process including consultation with healthcare staff and community members culminated in a systems-based model for improving access to CR in rural and remote areas. Results Poorly organised CR systems, poor client/staff understanding of discharge planning and low referral rates for secondary prevention, resulted in the majority of clients not accessing secondary prevention, despite resources being available. Revised health systems and management processes were recommended for the proposed Heart: Road to health model, and given common chronic diseases risk factors it was recommended to be broadened into Chronic disease: Road to health . Conclusion A Chronic disease: Road to health model could provide effective and efficient secondary prevention for people with chronic diseases in rural and remote areas. It is proposed that this approach could reduce gaps and duplication in current healthcare services and provide flexible, client-centred, holistic, culturally responsive services, and improve client outcomes.
Subject(s)
Health Services Accessibility , Rural Health Services , Secondary Prevention , Humans , Queensland/epidemiology , Secondary Prevention/methods , Chronic Disease/prevention & control , Rural Health Services/organization & administration , Interviews as Topic , Rural Population , Cardiac Rehabilitation/methods , Qualitative Research , Referral and Consultation , Heart Diseases/prevention & control , Female , Models, Organizational , MaleABSTRACT
In folk medicine, the almond nut (Terminalia catappa) and orange peel (Citrus sinensis) are cost-effective sources of nutraceutical utilized in the treatment of degenerative diseases. Hyperlipidemia and hypertension are two pathological conditions implicated in cardiovascular disorders. This study sought to evaluate the cardiomodulatory effect of almond-citrus peel fortified shortbread in hyperlipidemic-hypertensive rats induced by high fat diet and Nω-nitro-l-arginine methyl ester. The experimental animals were divided into eight groups. The experimental rats were fed with shortbread supplemented with almond and citrus peel at varying inclusions of 0.2% citrus, 50% almond, and almond (50%)- citrus (0.2%) for 21 days. The mean arterial blood pressure (MABP), systolic blood pressure (SBP), and lipid profile of the experimental rats were measured. Thereafter, the activities of angiotensin-1-converting enzyme (ACE), arginase, malondialdehyde (MDA), phosphodiesterase-5, nitric oxide (NO), and antioxidant indices were evaluated. The result showed significant elevation in SBP, MABP, blood cholesterol, triglyceride, ACE, arginase, activities, and MDA levels in the heart tissue of the untreated rats. In contrast, the antioxidant status and NO level were significantly decreased in the untreated groups. Remarkably, the treatment with almond-citrus peel fortified shortbread and the individual effect of almond (50%) and citrus peel (0.2%) all reversed these trends in the hyperlipidemic-hypertensive rats. Intriguingly, the blend of almond (50%)-citrus peel (0.2%) fortified shortbread showed the best antioxidative and cardioprotective effect. The results suggest that almond and citrus peel offer potentials as therapeutic agent in the prevention and management of hyperlipidemia and hypertension.
Subject(s)
Citrus , Heart Diseases , Prunus dulcis , Male , Animals , Rats , Rats, Wistar , Antioxidants/pharmacology , Prunus dulcis/chemistry , Citrus/chemistry , Hypertension , Heart Diseases/prevention & control , Hyperlipidemias , NG-Nitroarginine Methyl Ester/pharmacology , Diet, High-FatABSTRACT
INTRODUCTION: Anthracycline-based chemotherapy increases the risk of cancer therapeutics-related cardiac dysfunction. Recently, evidences from in vitro experiments and animal studies have shown that ginsenosides may exert cardiovascular protection against cancer therapeutics-related cardiac dysfunction. Here, we aimed to evaluate this effect in a clinical situation. METHODS: In this randomized, double-blind, placebo-controlled clinical trial, women with non-metastatic breast cancer whose left ventricular ejection fraction was ≥ 50% were randomly assigned in 1:1 ratio to receive ginseng (1â g/day) or placebo besides standard chemotherapy. Echocardiographic measurements were performed at baseline, after the fourth, and eighth chemotherapy cycles. High-sensitive cardiac troponin I was assessed at baseline and after the 4th cycle. The primary endpoint of the study was change in left ventricular ejection fraction. Cancer therapeutics-related cardiac dysfunction was defined as a drop in left ventricular ejection fraction of ≥ 10% from baseline. RESULTS: Results from 30 patients were included in the final analysis (15 patients in each group). In the intervention and control groups, left ventricular ejection fraction was dropped from 62.0 ± 0.9% to 60.7 ± 1.0% (difference = -1.3 ± 1.1%) and from 63.27 ± 1.1% to 58.0 ± 1.3% (difference = -5.27 ± 0.8%), respectively (difference = 3.97%, p = 0.006) at the end of the fourth cycle of chemotherapy. After the eighth cycle of chemotherapy, the mean left ventricular ejection fraction was increased by 0.8 ± 1.3% from baseline in the intervention group, whereas the placebo group experienced a reduction of -7.3 ± 1.4% (difference = 8.1%, p-value < 0.001). None of the patients in the ginseng group in comparison to 1(6.7%, p-value = 0.5) and 5 (33.3%, p-value = 0.02) patients in the placebo group developed cancer therapeutics-related cardiac dysfunction after the fourth and eighth cycles, respectively. High-sensitive cardiac troponin I levels were not significantly different between groups. CONCLUSIONS: Prophylactic ginseng supplementation may protect against doxorubicin-induced early cancer therapeutics-related cardiac dysfunction and early decline in left ventricular ejection fraction in breast cancer patients.
Subject(s)
Breast Neoplasms , Heart Diseases , Panax , Female , Humans , Anthracyclines/adverse effects , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cardiotoxicity/etiology , Cardiotoxicity/prevention & control , Doxorubicin/toxicity , Heart Diseases/chemically induced , Heart Diseases/prevention & control , Stroke Volume , Troponin I , Ventricular Function, LeftABSTRACT
The Effect of Diet on Cardiovascular Disease, Heart Disease, and Blood Vessels [...].
Subject(s)
Cardiovascular Diseases/prevention & control , Diet , Fatty Acids, Omega-3/pharmacology , Animals , Cardiotonic Agents/administration & dosage , Cardiotonic Agents/pharmacology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/genetics , Cholesterol, HDL/physiology , Fatty Acids, Omega-3/administration & dosage , Fructose/adverse effects , Gastrointestinal Microbiome/physiology , Heart Disease Risk Factors , Heart Diseases/etiology , Heart Diseases/prevention & control , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hypertension/etiology , Life Style , Lipoproteins, HDL/physiology , Obesity/complications , Rats , Risk Factors , Sodium Chloride, Dietary/adverse effects , Trans Fatty Acids/adverse effects , Vascular Diseases/etiology , Vascular Diseases/prevention & controlABSTRACT
Administration of Chemotherapeutics, especially doxorubicin (DOX) and cyclophosphamide (CPS), is commonly associated with adverse effects such as myelosuppression and cardiotoxicity. At this time, few approved therapeutic options are currently available for the management of chemotherapy-associated cardiotoxicity. Thus, identification of novel therapeutics with potent cardioprotective properties and minimal adverse effects are pertinent in treating Doxorubicin and Cyclophosphamide-induced cardiotoxicity. Oroxylum indicum extract (OIE, Sabroxy®) is a natural product known to possess several beneficial biological functions including antioxidant, anti-inflammatory and cytoprotective effects. We therefore set to investigate the cardioprotective effects of OIE against Doxorubicin and Cyclophosphamide-induced cardiotoxicity and explore the potential cardioprotective mechanisms involved. Adult male mice were treated with DOX and CPS in combination, OIE alone, or a combination of OIE and DOX & CPS. Swimming test was performed to assess cardiac function. Markers of oxidative stress were assessed by levels of reactive oxygen species (ROS), nitrite, hydrogen peroxide, catalase, and glutathione content. The activity of interleukin converting enzyme and cyclooxygenase was determined as markers of inflammation. Mitochondrial function was assessed by measuring Complex-I activity. Apoptosis was assessed by Caspase-3 and protease activity. Mice treated with DOX and CPS exhibited reduced swim rate, increased oxidative stress, increased inflammation, and apoptosis in the heart tissue. These cardiotoxic effects were significantly reduced by co-administration of OIE. Furthermore, computational molecular docking studies revealed potential binding of DOX and CPS to tyrosine hydroxylase which validated our in vivo findings regarding the inhibition of tyrosine hydroxylase activity. Our current findings indicated that OIE counteracts Doxorubicin and Cyclophosphamide-induced cardiotoxicity-through inhibition of ROS-mediated apoptosis and by blocking the effect on tyrosine hydroxylase. Taken together, our findings suggested that OIE possesses cardioprotective effects to counteract potentially fatal cardiac complications associated with chemotherapy treatment.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Bignoniaceae , Heart Diseases/prevention & control , Mitochondria, Heart/drug effects , Myocytes, Cardiac/drug effects , Plant Extracts/pharmacology , Animals , Anti-Inflammatory Agents/isolation & purification , Antioxidants/isolation & purification , Apoptosis/drug effects , Apoptosis Regulatory Proteins/metabolism , Bignoniaceae/chemistry , Cardiotoxicity , Cyclophosphamide , Disease Models, Animal , Doxorubicin , Heart Diseases/chemically induced , Heart Diseases/metabolism , Heart Diseases/pathology , Inflammation Mediators/metabolism , Male , Mice, Inbred C57BL , Mitochondria, Heart/metabolism , Mitochondria, Heart/pathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Oxidative Stress/drug effects , Plant Extracts/isolation & purification , Reactive Oxygen Species/metabolism , Tyrosine 3-Monooxygenase/antagonists & inhibitors , Tyrosine 3-Monooxygenase/metabolismABSTRACT
The goal of this work aimed to evaluate the protective effects of pea (Pisum sativum) peels extract versus doxorubicin-induced oxidative myocardial injury in male mice. The mice were divided into seven groups (n = 7): (I) control group; (II) P. sativum 250 group; (III) P. sativum 500 group; (IV) DOX (3 times alternately of 2.5 mg/kg/week, i.p. for a continuous two-week period) group; (V) Vit. E 100 + DOX group; (VI) P. sativum 250 + DOX group, and (VII) P. sativum 500 + DOX group). Twenty polyphenolic compounds, mainly flavonoid glycosides such as quercetin, kaempferol apigenin, and phenolics compounds were characterized by LC-MS/MS analysis in the examined extract. DOX administration elevated the activities of serum biomarkers of myocardial dysfunction (ALT, AST, ALP, LDH, troponin, CPK, and CK-MB), lipid profile, and proinflammatory cytokines. Also, it decreased cardiac antioxidants (GSH, SOD, GPX, CAT) and increased myocardial markers of oxidative stress (NO and MDA) and inflammatory marker (MPO). As well as it downregulated and upregulated the Bcl-2 (anti-apoptotic gene) and the Bax (pro-apoptotic gene) expressions, respectively. Pre-treatment of DOX-exposed mice with P. sativum or vitamin E (as a reference protective antioxidant) alleviated the changes dose-dependently via DOX-induced cardiotoxicity. These data show that P. sativum has a cardio-protective impact against DOX-induced cardiomyocyte damage in mice via boosting endogenous antioxidants, decreasing inflammation, and regulating BcL-2 and Bax apoptosis pathway, which might be related to the presence of flavonoid glycosides. P. sativum peels are a by-product that could be suggested for further screening as a possible new candidate for therapeutic use.
Subject(s)
Antioxidants/pharmacology , Heart Diseases/prevention & control , Myocytes, Cardiac/drug effects , Oxidative Stress/drug effects , Phytochemicals/pharmacology , Pisum sativum , Plant Extracts/pharmacology , Animals , Antioxidants/isolation & purification , Apoptosis/drug effects , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Cardiotoxicity , Disease Models, Animal , Doxorubicin , Heart Diseases/chemically induced , Heart Diseases/metabolism , Heart Diseases/pathology , Inflammation Mediators/metabolism , Male , Mice , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Pisum sativum/metabolism , Phytochemicals/isolation & purification , Plant Extracts/isolation & purification , Secondary Metabolism , Seeds , Signal TransductionABSTRACT
Background It is known that dietary intake of polyunsaturated fatty acids may improve cardiac function. However, relatively high daily doses are required to achieve sufficient cardiac concentrations of beneficial omega-3 fatty acids. The liver X receptor (LXR) is a nuclear hormone receptor and a crucial regulator of lipid homeostasis in mammals. LXR activation has been shown to endogenously reprogram cellular lipid profiles toward increased polyunsaturated fatty acids levels. Here we studied whether LXR lipid reprogramming occurs in cardiac tissue and exerts cardioprotective actions. Methods and Results Male 129SV mice were treated with the LXR agonist AZ876 (20 µmol/kg per day) for 11 days. From day 6, the mice were injected with the nonselective ß-agonist isoproterenol for 4 consecutive days to induce diastolic dysfunction and subendocardial fibrosis while maintaining systolic function. Treatment with isoproterenol led to a marked impairment of global longitudinal strain and the E/e' ratio of transmitral flow to mitral annular velocity, which were both significantly improved by the LXR agonist. Histological examination showed a significant reduction in isoproterenol-induced subendocardial fibrosis by AZ876. Analysis of the cardiac lipid composition by liquid chromatography-high resolution mass spectrometry revealed a significant increase in cardiac polyunsaturated fatty acids levels and a significant reduction in saturated fatty acids by AZ876. Conclusions The present study provides evidence that the LXR agonist AZ876 prevents subendocardial damage, improves global longitudinal strain and E/e' in a mouse model of isoproterenol-induced cardiac damage, accompanied by an upregulation of cardiac polyunsaturated fatty acids levels. Cardiac LXR activation and beneficial endogenous cardiac lipid reprogramming may provide a new therapeutic strategy in cardiac disease with diastolic dysfunction.
Subject(s)
Aniline Compounds/pharmacology , Fatty Acids/metabolism , Heart Diseases/prevention & control , Isoproterenol , Myocardium/metabolism , Thiazoles/pharmacology , Animals , Cellular Reprogramming , Disease Models, Animal , Fibrosis , Heart Diseases/chemically induced , Heart Diseases/pathology , Liver X Receptors/agonists , Male , Mice , Mice, 129 Strain , Myocardium/pathologyABSTRACT
Heart failure (HF) is the advanced heart disease with high morbidity and mortality. Compound DanShen Dripping Pill (CDDP) is a widely used Traditional Chinese Medicine for cardiovascular disease treatment. Herein, we investigated if CDDP can protect mice against doxorubicin (DOX) or isoprenaline (ISO)-induced HF. After 3 days feeding of normal chow containing CDDP, mice were started DOX or ISO treatment for 4 weeks or 18 days. At the end of treatment, mice were conducted electrocardiogram and echocardiographic test. Blood and heart samples were determined biochemical parameters, myocardial structure and expression of the related molecules. CDDP normalized DOX/ISO-induced heart weight changes, HF parameters and fibrogenesis. The DOX/ISO-impaired left ventricular ejection fraction and fractional shortening were restored by CDDP. Mechanistically, CDDP blocked DOX/ISO-inhibited expression of antioxidant enzymes and DOX/ISO-induced expression of pro-fibrotic molecules, inflammation and cell apoptosis. Additional DOX/ISO-impaired targets in cardiac function but protected by CDDP were identified by RNAseq, qRT-PCR and Western blot. In addition, CDDP protected cardiomyocytes against oxygen-glucose deprivation-induced injuries. Taken together, our study shows that CDDP can protect against myocardial injuries in different models, suggesting its potential application for HF treatment.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Drugs, Chinese Herbal/pharmacology , Heart Diseases/prevention & control , Myocytes, Cardiac/drug effects , Animals , Apoptosis/drug effects , Camphanes , Cardiotoxicity , Cell Line , Disease Models, Animal , Doxorubicin , Fibrosis , Heart Diseases/chemically induced , Heart Diseases/metabolism , Heart Diseases/pathology , Inflammation Mediators/metabolism , Isoproterenol , Male , Mice, Inbred C57BL , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Oxidative Stress/drug effects , Panax notoginseng , Rats , Salvia miltiorrhiza , Stroke Volume/drug effects , Ventricular Function, Left/drug effectsABSTRACT
For nearly 2 decades, regulators have adopted a harmonized approach to drug development, which has succeeded in bringing new pharmaceuticals to market without significant cardiac liability. Ushered in by technological advancements and better understanding of cellular electrophysiology, the initial paradigm detailed in the 2005 International Conference for Harmonization E14 and S7B documents has undergone evolutionary changes designed to streamline drug development and improve regulatory decision-making and product labeling. The intent of this review is to summarize the new US Food and Drug Administration (FDA) Question and Answer update from August 2020 and key messaging from a subsequent FDA webinar describing best practices for preclinical and clinical data integration into a QT risk prediction model.
Subject(s)
Cardiotoxicity/prevention & control , Drug Development/legislation & jurisprudence , Heart Diseases/prevention & control , Animals , Drug Development/methods , Drug Evaluation, Preclinical/methods , Drug Labeling/legislation & jurisprudence , Heart Diseases/chemically induced , Humans , United States , United States Food and Drug AdministrationABSTRACT
To evaluate whether lowering plasma homocysteine (Hcy) levels at different doses of folic acid (FA) could reduce cardiac fibrosis and diastolic dysfunction in spontaneously hypertensive rats (SHRs) with hyperhomocysteinemia (Hhcy) and investigate the possible mechanism of action.We randomly divided 32 male SHRs into control, Hhcy, Hhcy + low-dose FA (LFA), and Hhcy + high-dose FA (HFA) groups. Echocardiography and Masson staining of cardiac tissue were used to assess diastolic function and cardiac fibrosis. Blood pressure (BP) and Hcy levels were measured during the experiment. We also measured the indicators of oxidative stress (OS) and examined the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) genes and proteins using real-time polymerase chain reaction (PCR), immunohistochemistry, and western blotting to explore the possible mechanism of action.FA treatment reversed SHR cardiomyocyte interstitial and perivascular collagen deposition and diastolic dysfunction exacerbated by Hhcy. These effects were associated with promoting the translocation of Nrf2 from the cytoplasm to the nucleus, activating HO-1 expression and inhibiting OS. However, HFA did not show any additional benefit from LFA in reducing cardiac injury.Even at a low dose, FA can ameliorate Hhcy-induced cardiac fibrosis and diastolic dysfunction in SHRs by activating Nrf2/HO-1 pathway and inhibiting OS, independent of BP, providing evidence for the efficacy of LFA in the treatment of hypertension associated with Hhcy.
Subject(s)
Folic Acid/therapeutic use , Heart Diseases/prevention & control , Hematinics/therapeutic use , Hyperhomocysteinemia/complications , Hypertension/complications , Animals , Diastole , Drug Evaluation, Preclinical , Fibrosis , Heart/physiopathology , Heart Diseases/pathology , Heart Diseases/physiopathology , Male , Myocardium/pathology , Random Allocation , Rats, Inbred SHRABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: The genus Hypericum are widely distributed in China. Hypericum perforatum L. (genus Hypericum, family Hypericaceae) has a long history as a traditional Chinese medicine, which was traditionally used for the treatment of emotional distress, cardiothoracic depression, and acute mastitis. Hyperoside (Hyp) extracted from Hypericum perforatum L. has been affirmed to exert therapeutic effects on cardiovascular diseases, with widespread existence in plants of genus Hypericum. Hyp could also be extracted from Crataegus pinnatifida Bunge (genus Crataegus pinnatifida Bunge, family Rosaceae), another traditional Chinese medicine that traditionally prevented and treated heart disease in China. The cardioprotection and mechanism of Hyp comprise anti-inflammation, anti-fibrosis, activation of autophagy, and reversal of cardiac remodeling. AIM OF THE STUDY: This study aimed to explore the Hyp effect against MI and its underlying mechanism. MATERIALS AND METHODS: The MI model was constructed in the KM mice via a ligating surgery of the left anterior descending (LAD) coronary artery. Subsequently, the mice were divided into following seven groups: Sham group, MI group, MI + Hyp 9 mg/kg group, MI + Hyp18 mg/kg group, MI + Hyp36 mg/kg group, MI + Fosinopril group, and MI + Hyp-36 mg/kg+3-MA group. Each group was treated with Hyp in different concentrations or positive medicine for two weeks except for the sham group. After two weeks, we examined the cardiac function, electrocardiogram (ECG), myocardial hypertrophy in the non-infarct area, collagen volume fraction (CVF), perivascular collagen area (PVCA) in the infarct area, and several serum cytokines. Autophagy and inflammation in cardiomyocytes were assessed via measuring autophagy-associated proteins and NLRP1 inflammasome pathway related proteins. RESULTS: Hyp reversed LV remodeling and adverse ECG changes through reducing CVF and myocardial hypertrophy. Additionally, Hyp treatment could reduce inflammation levels in cardiomyocytes, compared with those in MI group. Moreover, NLRP1inflammation pathway was activated after MI. Up-regulation of autophagic flux suppressed NLRP1 inflammation pathway after Hyp treatment. However, co-treatment with 3-MA abrogated above effects of Hyp. CONCLUSIONS: Hyp had obvious protective effect on heart injury in MI mice. Echocanrdiographic and histological measurements demonstrated that Hyp treatment improved cardiac function, and ameliorated myocardial hypertrophy and fibrinogen deposition after MI. The partial mechanism is that Hyp could up-regulate autophagy after MI. Furthermore, the promotion of autophagic flux would suppress NLRP1 inflammation pathway induced by MI.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Apoptosis Regulatory Proteins/metabolism , Autophagy/drug effects , Cardiotonic Agents/pharmacology , Inflammation/prevention & control , Myocardial Infarction/prevention & control , Quercetin/analogs & derivatives , Animals , Body Weight/drug effects , Cardiotonic Agents/therapeutic use , Cytokines/blood , Disease Models, Animal , Electrocardiography/drug effects , Heart Diseases/etiology , Heart Diseases/prevention & control , Hypericum/chemistry , Inflammation/metabolism , Male , Medicine, Chinese Traditional , Myocardial Infarction/complications , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Myocytes, Cardiac/drug effects , Organ Size/drug effects , Quercetin/pharmacology , Quercetin/therapeutic use , Signal Transduction/drug effects , Ventricular Remodeling/drug effectsABSTRACT
BACKGROUND: Doxorubicin (DOX) is a commonly used chemotherapeutic drug but is limited in clinical applications by its cardiotoxicity. Neiguan acupoint (PC6) is a well-recognized acupoint for the treatment of cardiothoracic disease. However, whether acupuncture at PC6 could be effective in preventing DOX-induced cardiotoxicity is still unknown. METHODS: A set of experiments were performed with myocardial cells, wild type, inducible nitric oxide synthase knockout (iNOS-/-), and myocardial-specific ablation arginase 2 (Myh6-ARG 2-/-) mice. We investigated the protective effect and the underlying mechanisms for electroacupuncture (EA) against DOX-induced cardiotoxicity by echocardiography, immunostaining, biochemical analysis, and molecular biotechnology in vivo and in vitro analysis. RESULTS: We found that DOX-mediated nitric oxide (NO) production was positively correlated with the iNOS level but has a negative correlation with the arginase 2 (ARG 2) level in both myocardial cells and tissues. Meanwhile, EA at PC6 alleviated cardiac dysfunction and cardiac hypertrophy in DOX-treated mice. EA at PC6 blocked the upregulation of NO production in accompanied with the downregulated iNOS and upregulated ARG 2 levels in myocardial tissue induced by DOX. Furthermore, knockout iNOS prevented cardiotoxicity and EA treatment did not cause the further improvement of cardiac function in iNOS-/- mice treated by DOX. In contrast, deficiency of myocardial ARG 2 aggravated DOX-induced cardiotoxicity and reduced EA protective effect. CONCLUSION: These results suggest that EA treatment at PC6 can prevent DOX-induced cardiotoxicity through modulating NO production by modulating the iNOS/ARG 2 balance in myocardial cells.
Subject(s)
Antineoplastic Agents/toxicity , Arginase/metabolism , Doxorubicin/toxicity , Electroacupuncture/methods , Heart Diseases/prevention & control , Nitric Oxide Synthase Type II/metabolism , Acupuncture Points , Animals , Arginase/genetics , Cardiotoxicity/etiology , Cardiotoxicity/parasitology , Heart Diseases/etiology , Male , Mice , Mice, Inbred C57BL , Myocardium/metabolism , Nitric Oxide Synthase Type II/genetics , Signal TransductionABSTRACT
Coronary artery diseases are the major causes of disabilities and death worldwide. Evidence from the literature has demonstrated that Origanum majorana L. (marjoram) acts as an antioxidant, anti-inflammatory, antiplatelet, and assists in hormonal regulation. However, there is limited scientific evidence describing the signaling pathways associated with the marjoram's positive effect on cardiac injury. Therefore, we aimed to understand the mechanistic protective effects of marjoram on isoproterenol (ISO)-induced myocardial injury in rats. Sprague Dawley rats were randomly assigned into six groups. Marjoram was administrated by oral gavage and isoproterenol was administrated subcutaneously (ISO; 85 mg/kg). Heart weight, cardiac enzymes, inflammatory, and oxidative stress biomarkers were measured. The ISO-induced cardiac injury was confirmed by the significant increase in the levels of cardiac enzymes (P value < 0.05), whereas pre-treatment with marjoram normalized these cardiac injury parameters. We also determined that marjoram had a protective effect against ISO-induced increase in C-reactive protein (CRP), IL-6, IL-13, and TNF-α. Additionally, marjoram significantly decreased cardiac thiobarbituric acid reactive substances (TBARS) levels (P value < 0.05) and protected against ISO-induced oxidative stress. We have demonstrated that marjoram decreased both cardiac oxidative stress and inflammation, thus establishing the beneficial effects of marjoram on ISO-induced cardiac injury in rats.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Heart Diseases/prevention & control , Inflammation Mediators/metabolism , Myocytes, Cardiac/drug effects , Origanum , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Animals , Anti-Inflammatory Agents/isolation & purification , Antioxidants/isolation & purification , Biomarkers/metabolism , Cardiotoxicity , Disease Models, Animal , Fibrosis , Heart Diseases/chemically induced , Heart Diseases/metabolism , Heart Diseases/pathology , Isoproterenol , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Origanum/chemistry , Plant Extracts/isolation & purification , Rats, Sprague-Dawley , Signal TransductionABSTRACT
Offspring born to diabetic or obese mothers have a higher lifetime risk of heart disease. Previously, we found that rat offspring exposed to late-gestational diabetes mellitus (LGDM) and maternal high-fat (HF) diet develop mitochondrial dysfunction, impaired cardiomyocyte bioenergetics, and cardiac dysfunction at birth and again during aging. Here, we compared echocardiography, cardiomyocyte bioenergetics, oxidative damage, and mitochondria-mediated cell death among control, pregestational diabetes mellitus (PGDM)-exposed, HF-diet-exposed, and combination-exposed newborn offspring. We hypothesized that PGDM exposure, similar to LGDM, causes mitochondrial dysfunction to play a central, pathogenic role in neonatal cardiomyopathy. We found that PGDM-exposed offspring, similar to LGDM-exposed offspring, have cardiac dysfunction at birth, but their isolated cardiomyocytes have seemingly less bioenergetics impairment. This finding was due to confounding by impaired viability related to poorer ATP generation, more lipid peroxidation, and faster apoptosis under metabolic stress. To mechanistically isolate and test the role of mitochondria, we transferred mitochondria from normal rat myocardium to control and exposed neonatal rat cardiomyocytes. As expected, transfer provides a respiratory boost to cardiomyocytes from all groups. They also reduce apoptosis in PGDM-exposed males, but not in females. Findings highlight sex-specific differences in mitochondria-mediated mechanisms of developmentally programmed heart disease and underscore potential caveats of therapeutic mitochondrial transfer.
Subject(s)
Diabetes Mellitus, Experimental/complications , Diabetes, Gestational/physiopathology , Energy Metabolism , Heart Diseases/prevention & control , Mitochondria/transplantation , Myocytes, Cardiac/cytology , Myocytes, Cardiac/physiology , Animals , Diet, High-Fat/adverse effects , Female , Heart Diseases/etiology , Heart Diseases/pathology , Male , Maternal Nutritional Physiological Phenomena , Pregnancy , Prenatal Exposure Delayed Effects/etiology , Prenatal Exposure Delayed Effects/pathology , Prenatal Exposure Delayed Effects/prevention & control , Rats , Rats, Sprague-Dawley , Sex FactorsABSTRACT
The cardiotoxicity of chemotherapeutic drugs as cisplatin has become a major issue in recent years. The present study investigates the efficacy of curcumin nanoparticles against the cardiotoxic effects of cisplatin by assessment of oxidative stress parameters, Na+,K+-ATPase, acetylcholinesterase (AchE) and tumor necrosis factor-alpha (TNF-α) in cardiac tissue in addition to serum lactate dehydrogenase (LDH). Rats were divided into three groups: control rats that received saline for 14 days; cisplatin-treated rats that received a single intraperitoneal (i.p.) injection of cisplatin (12 mg/kg) followed by a daily oral administration of saline (0.9%) for 14 days and rats treated with a single i.p. injection of cisplatin (12 mg/kg) followed by a daily oral administration of curcumin nanoparticles (50 mg/kg) for 14 days. Cisplatin resulted in a significant increase in lipid peroxidation, nitric oxide (NO), and TNF-α and a significant decrease in reduced glutathione (GSH) levels and Na+, K+- ATPase activity. Moreover, significant increases in cardiac AchE and serum lactate dehydrogenase activities were recorded. Treatment of cisplatin-injected animals with curcumin nanoparticles ameliorated all the alterations induced by cisplatin in the heart of rats. This suggests that curcumin nanoparticles can be used as an important therapeutic adjuvant in chemotherapeutic and other toxicities mediated by oxidative stress and inflammation.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Curcumin/pharmacology , Heart Diseases/prevention & control , Myocytes, Cardiac/drug effects , Nanoparticles , Acetylcholinesterase/metabolism , Animals , Cisplatin , Disease Models, Animal , GPI-Linked Proteins/metabolism , Heart Diseases/chemically induced , Heart Diseases/metabolism , Heart Diseases/pathology , Lipid Peroxidation/drug effects , Male , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Oxidative Stress/drug effects , Rats, Wistar , Sodium-Potassium-Exchanging ATPase/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
BACKGROUND: There are few evidence-based strategies to attenuate the risk of metabolic syndrome in offspring exposed to gestational diabetes mellitus (GDM). Berberine (BBR) is an isoquinoline alkaloid extracted from Chinese herbs and exhibits glucose lowering properties. OBJECTIVES: We hypothesized that dietary BBR would improve health outcomes in the mouse offspring of GDM dams. METHODS: Wild-type C57BL/6 female mice were fed either a Lean-inducing low-fat diet (L-LF,10% kcal fat, 35% kcal sucrose) or a GDM-inducing high-fat diet (GDM-HF, 45% kcal fat, 17.5% sucrose) for 6 wk prior to breeding with wild-type C57BL/6 male mice throughout pregnancy and the suckling period. The resulting Lean and GDM-exposed male and female offspring were randomly assigned an LF (10% kcal fat, 35% kcal sucrose), HF (45% kcal fat, 17.5% sucrose), or high-fat berberine (HFB) (45% kcal fat, 17.5% sucrose diet) containing BBR (160 mg/kg/d, HFB) at weaning for 12 wk. The main outcome was to evaluate the effects of BBR on obesity, pancreatic islet function, and cardiac contractility in GDM-exposed HF-fed offspring. Significance between measurements was determined using a 2 (gestational exposure) × 3 (diet) factorial design by a 2- way ANOVA using Tukey post-hoc analysis. RESULTS: In the GDM-HF group, body weights were significantly increased (16%) compared with those in baseline (L-LF) animals (P < 0.05). Compared with the L-LF animals, the GDM-HF group had a reduction in pancreatic insulin glucose-stimulated insulin secretion (74%) and increased cardiac isovolumetric contraction time (IVCT; â¼150%) (P < 0.05). Compared with GDM-HF animals, the GDM-HFB group with the dietary addition of BBR had significantly reduced body weight (16%), increased glucose-stimulated insulin secretion from pancreatic islets (254%), and reduced systolic heart function (46% IVCT) (P < 0.05). CONCLUSIONS: In a mouse model of GDM, dietary BBR treatment provided protection from obesity and the development of pancreatic islet and cardiac dysfunction.
Subject(s)
Berberine/administration & dosage , Diabetes, Gestational/diet therapy , Diet, High-Fat/adverse effects , Dietary Supplements , Adiposity/drug effects , Animals , Body Weight/drug effects , Female , Glucose/metabolism , Heart Diseases/prevention & control , Insulin/blood , Insulin/metabolism , Islets of Langerhans/drug effects , Islets of Langerhans/metabolism , Male , Mice , Mice, Inbred C57BL , Mitochondria, Heart/drug effects , Mitochondria, Heart/metabolism , Obesity/prevention & control , Pregnancy , Prenatal Exposure Delayed Effects/diet therapyABSTRACT
Obesity is growing at an alarming rate, which is characterized by increased adipose tissue. It increases the probability of many health complications, such as diabetes, arthritis, cardiac disease, and cancer. In modern society, with a growing population of obese patients, several individuals have increased insulin resistance. Herbal medicines are known as the oldest method of health care treatment for obesity-related secondary health issues. Several traditional medicinal plants and their effective phytoconstituents have shown anti-diabetic and anti-adipogenic activity. Adipose tissue is a major site for lipid accumulation as well as the whole-body insulin sensitivity region. 3T3-L1 cell line model can achieve adipogenesis. Adipocyte characteristics features such as expression of adipocyte markers and aggregation of lipids are chemically induced in the 3T3-L1 fibroblast cell line. Differentiation of 3T3-L1 is an efficient and convenient way to obtain adipocyte like cells in experimental studies. Peroxisome proliferation activated receptor γ (PPARγ) and Cytosine-Cytosine-Adenosine-Adenosine-Thymidine/Enhancer-binding protein α (CCAAT/Enhancer-binding protein α or C/EBPα) are considered to be regulating adipogenesis at the early stage, while adiponectin and fatty acid synthase (FAS) is responsible for the mature adipocyte formation. Excess accumulation of these adipose tissues and lipids leads to obesity. Thus, investigating adipose tissue development and the underlying molecular mechanism is important in the therapeutical approach. This review describes the cellular mechanism of 3T3-L1 fibroblast cells on potential anti-adipogenic herbal bioactive compounds.
Subject(s)
Anti-Obesity Agents/therapeutic use , Arthritis/prevention & control , Diabetes Mellitus/prevention & control , Heart Diseases/prevention & control , Neoplasms/prevention & control , Obesity/drug therapy , Phytochemicals/therapeutic use , 3T3-L1 Cells , Adipogenesis/drug effects , Adipogenesis/genetics , Adiponectin/genetics , Adiponectin/metabolism , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Adipose Tissue/pathology , Animals , Anti-Obesity Agents/chemistry , Arthritis/etiology , Arthritis/genetics , Arthritis/pathology , CCAAT-Enhancer-Binding Proteins/genetics , CCAAT-Enhancer-Binding Proteins/metabolism , Diabetes Mellitus/etiology , Diabetes Mellitus/genetics , Diabetes Mellitus/pathology , Fatty Acid Synthases/genetics , Fatty Acid Synthases/metabolism , Gene Expression Regulation , Heart Diseases/etiology , Heart Diseases/genetics , Heart Diseases/pathology , Humans , Insulin Resistance , Mice , Neoplasms/etiology , Neoplasms/genetics , Neoplasms/pathology , Obesity/complications , Obesity/genetics , Obesity/pathology , PPAR gamma/genetics , PPAR gamma/metabolism , Phytochemicals/chemistryABSTRACT
OBJECTIVES: Cardiovascular diseases are major causes of non-infectious diseases globally. The use of pesticides has been linked with the high global burden of non-communicable diseases. Despite the indiscriminate exposure to dichlorvos (DDVP) by inhalation, no report exists on its possible cardiotoxic effect. This study investigated the cardiotoxicity of DDVP exposure by inhalation and the possible role of Moringa oleifera seed oil. METHODS: Twenty-one male rats were randomly assigned into 3 groups. Group A (control) received only standard rat diet and water ad' libitum, group B (DDVP) was exposed to DDVP via inhalation for 15 min daily in addition to rat diet and water, and group C (DDVP + M. oleifera seed oil) received treatment as group B as well as 300 mg/kg of M. oleifera seed oil p.o for 28 days. RESULTS: Significant reductions in body weight gain and cardiac weight were observed in DDVP-exposed animals (p<0.05). Similarly, 28 days of exposure to DDVP led to a significant increase in lactate dehydrogenase, creatinine kinase and troponin (p<0.05). DDVP-exposed rats also showed a significant increase in malondialdehyde, and a significant decline in superoxide dismutase and glutathione peroxidase (p<0.05). However, catalase was comparable in DDVP-exposed and control rats. Histopathological observations of the cardiac tissue revealed that DDVP caused marked fat degeneration and necrosis of the myocardial layer. The changes in DDVP-exposed rats were significantly, though not completely, restored by M. oleifera seed oil administration. CONCLUSIONS: This study provides novel mechanistic information on the cardiotoxicity of DDVP inhalation, and the antioxidant potential of M. oleifera seed oil.
Subject(s)
Heart Diseases/prevention & control , Moringa oleifera , Plant Oils/pharmacology , Animals , Dichlorvos/pharmacology , Heart Diseases/chemically induced , Male , Oxidative Stress/drug effects , Random Allocation , Rats , Rats, Wistar , SeedsABSTRACT
The global burden of atherothrombotic heart disease should be considered as a life-style disorder where differences in dietary habits and related risk factors like limited physical activity and adiposity together play important roles. Related metabolic changes have been scientifically elucidated in recent decades, and the role of the very-long-chain marine fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been much focused on, especially their possible effects on processes like inflammation and thrombosis. In the present brief review of related metabolic mechanisms, the effects of these fatty acids in a clinical setting have been referred to, including some of the authors' work on this topic. The main focus is the divergent results in the field and the important differences between the study population, the type of supplements and fresh marine sources, the proportion of EPA versus DHA dosages, and the duration of supplementation in clinical trials. We conclude that daily intake of at least 1 g of EPA + DHA may improve a dysmetabolic state in the population. The potential to reduce the risk and progression of atherothrombotic heart disease is still a matter of debate.
Subject(s)
Dietary Supplements , Docosahexaenoic Acids/pharmacology , Eicosapentaenoic Acid/pharmacology , Fatty Acids, Omega-3/pharmacology , Heart Diseases/prevention & control , Clinical Trials as Topic , Coronary Artery Disease/prevention & control , Coronary Thrombosis/prevention & control , Diet, Healthy/methods , Eating/physiology , Heart Disease Risk Factors , Humans , Seafood/analysisABSTRACT
BACKGROUND: Cardiac adverse events are common among patients presenting with acute stroke and contribute to overall morbidity and mortality. Prophylactic measures for the reduction of cardiac adverse events in hospitalized stroke patients have not been well understood. We sought to investigate the effect of early initiation of high-dose intravenous magnesium sulfate on cardiac adverse events in stroke patients. METHODS: This is a secondary analysis of the prehospital Field Administration of Stroke Therapy-Magnesium (FAST-MAG) randomized phase-3 clinical trial, conducted from 2005-2013. Consecutive patients with suspected acute stroke and a serum magnesium level within 72 hours of enrollment were selected. Twenty grams of magnesium sulfate or placebo was administered in the ambulance starting with a 15-minute loading dose intravenous infusion followed by a 24-hour maintenance infusion in the hospital. RESULTS: Among 1126 patients included in the analysis of this study, 809 (71.8%) patients had ischemic stroke, 277 (24.6%) had hemorrhagic stroke, and 39 (3.5%) with stroke mimics. The mean age was 69.5 (SD13.4) and 42% were female. 565 (50.2%) received magnesium treatment, and 561 (49.8%) received placebo. 254 (22.6%) patients achieved the target, and 872 (77.4%) did not achieve the target, regardless of their treatment group. Among 1126 patients, 159 (14.1%) had at least one CAE. Treatment with magnesium was not associated with fewer cardiac adverse events. A multivariate binary logistic regression for predictors of CAEs showed a positive association of older age and frequency of CAEs (R = 1.04, 95% CI 1.03-1.06, p < 0.0001). Measures of early and 90-day outcomes did not differ significantly between the magnesium and placebo groups among patients who had CAEs. CONCLUSION: Treatment of acute stroke patients with magnesium did not result in a reduction in the number or severity of cardiac serious adverse events.