Cichorium intybus attenuates streptozotocin induced diabetic cardiomyopathy via inhibition of oxidative stress and inflammatory response in rats manju sharma 1, 4, aiman afaque 1, shridhar dwivedi 2, zeeba s. The pathophysiology of diabetic cardiomyopathy is incompletely understood but appears to be multifactorial in origin. There are evidences that the activation of ampk is playing pivotal role in the lipid and glucose metabolism. It is pointed out that the activation of the sympathetic nervous system and reninangiotensin system generates oxidative stress, which produces defects in subcellular organelles including sarcolemma, sarcoplasmic reticulum and myofibrils. Overexpression of metallothionein reduces diabetic cardiomyopathy. Maintaining myocardial glucose utilization in diabetic. Simvastatin is a lipidlowering agent used to treat hypercholesterolemia and to reduce the risk of heart disease. Oxidative stress and functional deficit in diabetic. Thus, increased oxidative stress in the heart may be implicated in the development of dilated cardiomyopathy in stzdiabetic rats. Cardiac oxidative stress is elevated at the onset of dilated. It is characterized by myocardial dilatation and hypertrophy as well as a decrease in the systolic and diastolic functions of the left ventricle, and its presence is independent of the coexistence of ischemic heart disease or hypertension. Several cellular signaling pathways are activated by oxidative stress or vice versa, and both can serve as important targets for the treatment of diabetic cardiomyopathy.
Pdcd4 deficiency ameliorates left ventricular remodeling and. Hyperglycemiainduced oxidative stress and fibrosis play a crucial role in the development of diabetic cardiomyopathy dcm. However, there is currently no effective strategy to prevent the development of dcm. Several hypotheses have been proposed, including oxidative stress, inflammation, endothelial dysfunction, metabolic derangements, abnormalities in ion homeostasis, alterations in structural proteins, and interstitial fibrosis. Improvements in the treatment of noncardiac complications from diabetes have resulted in heart disease becoming a leading cause of death in diabetic patients.
Igf1 overexpression inhibits the development of diabetic. Therapeutic targeting of oxidative stress with coenzyme. Diabetic cardiomyopathy an overview sciencedirect topics. Impact statement diabetic cardiomyopathy dcm is an important cause of heart failure in patients with diabetes, resulting in increased morbidity and mortality. Cardiac oxidative stress, lipotoxicity, inflammation, and the accumulation of misfolded proteins impair the function of cardiac endoplasmic reticulum and promote endoplasmic reticulum stress, inducing the unfolded protein response. In maternal diabetes, 90% of pregnancy losses happen in the first trimester due to oxidative stress. Diabetic cardiomyopathy dcm is an independent clinical entity defined as structural and functional changes in the myocardium because of metabolic and cellular abnormalities induced by diabetes, resulting in cardiac failure.
Curcumin analog a alleviates oxidative stress by activating. Role of oxidative stress in metabolic and subcellular. Reports suggest mixed effectiveness of antioxidants against the cardiac effects of dm. Oxidative stress and diabetic cardiomyopathy springerlink. Diabetic cardiomyopathy dcm is a specific myocardial disease, first described in 1972 in a patient with a history of dm and a wide range of cardiac structural abnormalities. Mar 03, 2010 the pathophysiology of diabetic cardiomyopathy is incompletely understood but appears to be multifactorial in origin. Oxidative stress and diabetic cardiomyopathy oxidative stress and diabetic cardiomyopathy cai, lu. Diabetic cardiomyopathy and oxidative stress sciencedirect. The pathophysiological factors in diabetes that drive the development of cardiomyopathy include systemic metabolic disorders, inappropriate activation of the reninangiotensinaldosteronesystem,subcellular component abnormalities, oxidative stress, inflammation and dysfunctional immune modulation. Diabetic cardiomyopathy dcm is the principal cause of death in people with diabetes. Oxidative stress plays a pivotal role in the development of diabetes complications, both microvascular and cardiovascular.
To directly evaluate the relationship between glucose delivery and mitochondrial dysfunction in diabetic cardiomyopathy we generated transgenic mice with inducible cardiomyocyte. In streptozotocininduced diabetes, there is a decrease in antioxidant enzyme activities and an increase in myocardial lipid peroxidation. Therapeutic interventions to prevent calcium accumulation and oxidative stress could be therefore helpful in improving the cardiac function under. Diabetic embryopathy may result in early or late spontaneous abortion and stillbirth. Mitochondrial dysfunction and oxidative stress in heart disease.
Myricitrin alleviates oxidative stressinduced inflammation. Role of differential signaling pathways and oxidative. Jairajpuri 3, yasmeen shamsi 5, mohd faiyaz khan 6, mohd ibrahim khan 7 and danish ahmed danish. Diabetes was induced by intraperitoneal injection of streptozotocin and both control and. The role of oxidative stress in the development of diabetic. The metabolic abnormalities of diabetes cause mitochondrial superoxide overproduction in endothelial cells of both large and small vessels, as well as in the myocardium. Hyperglycemia induces chronic inflammation and oxidative stress in cardiomyocyte, which are the main pathological changes of diabetic cardiomyopathy dcm. The increasing incidence of diabetes in young individuals is particularly worrisome given that the disease is likely to evolve over a. Programmed cell death 4 pdcd4 is a novel inflammation and apoptosis gene, but its role in type 2 dcm remains elusive. Double staining for cardiomyocytes with alpha sarcomeric actin and caspase3 or 3nt con.
Oxidative stress and diabetic cardiomyopathy, cardiovascular. Mechanisms of oxidative stress leading to cardiac tissue damage chronic hyperglycemia is strongly associated with enhanced oxidative stressinduced myocardial injury, 20. Cannabinoid 1 receptor promotes cardiac dysfunction. Keywords streptozotocindiabetic rats, oxidative stress, dilated cardiomyopathy, nitric oxide synthase activity, enosinos.
Diabetic cardiomyopathy was characterized by increased myocardial endocannabinoid anandamide levels, oxidativenitrative. Diabetic cardiomyopathy is a clinical problem that develops in diabetes, and potentially involves oxidative stress, myocyte death, cardiac hypertrophy and fibrosis. Oxidative stress has been suggested to play a role in the pathogenesis of diabetic cardiomyopathy. Numerous studies demonstrated that ameliorating oxidative stress through antioxidant treatment might be an effective strategy for reducing dcm 14, 15. Tetrahydrocurcumin thc, a major bioactive metabolite of natural antioxidant curcumin, is reported to exert even more effective antioxidative and superior antifibrotic properties as well as antiinflammatory and antidiabetic abilities. Diabetic embryopathy abortions in the secondtrimester are most likely due to severe birth defect, maternal metabolic derangement, placental insufficiency. Although several pathological mechanisms responsible for diabetic cardiomyopathy have been proposed, oxidative stress is widely considered as one of the. Diabetic cardiomyopathy as an important threat to health occurs with or without coexistence of vascular diseases. Although several pathological mechanisms responsible for diabetic cardiomyopathy have been proposed, oxidative stress is widely considered as one of the major causes for the pathogenesis of the disease. Diabetic cardiomyopathy and oxidative stress request pdf. However, hyperglycemia, as an independent risk factor, directly causes. Endoplasmic reticulum stress and increased cell death in diabetic cardiomyopathy.
Hyperglycemia has been seen as a major cause of dcm due to activation of different mechanisms leading to oxidative stress. Cardiac glucose uptake and oxidation are reduced in diabetes despite hyperglycemia. Keywords streptozotocin diabetic rats, oxidative stress, dilated cardiomyopathy, nitric oxide synthase activity, enosinos. Ijms free fulltext role of oxidative stress in metabolic. Diabetes induced cardiac complications include left ventricular lv dysfunction and heart failure. Azelnidipine prevents cardiac dysfunction in streptozotocin. Several cardiovascular pathological consequences of diabetes such as hypertension affect the heart to varying degrees.
Diabetic cardiomyopathy was characterized by increased myocardial endocannabinoid anandamide levels, oxidative nitrative. These pathogenic changes may contribute to compromised ventricular dysfunction in diabetes, which is one. The exact mechanisms underlying the disease remain incompletely clear. We aimed to determine if pdcd4 intervention improves dcm by affecting left ventricular.
Original article cannabinoid 1 receptor promotes cardiac. In this study, we explored the role of cb1 receptors in myocardial dysfunction, inflammation, oxidative nitrative stress, cell death, and interrelated signaling pathways, using a mouse model of type 1 diabetic cardiomyopathy. Simvastatin ameliorates diabetic cardiomyopathy by. In order to demonstrate that cardiac dysfunction in diabetes occurs progressively, and to examine the relationship between heart dysfunction and subcellular abnormalities, we have previously reported. Role of oxidative stress in the pathogenesis of diabetic cardiomyopathy. Objective diabetic cardiomyopathy dcm is characterized by cardiac remodeling, dysfunction, and insulin resistance. Numerous evidences suggest that diabetic heart is characterized by compromised ventricular contraction and prolonged relaxation attributable to multiple causative factors including calcium accumulation, oxidative stress and apoptosis. Apr 14, 2020 diabetic cardiomyopathy dcm is the principal cause of death in people with diabetes.
This study scrutinized the beneficial effects of simvastatin on experimental diabetic cardiomyopathy dcm, pointing to the role of hyperglycemiainduced oxidative stress and inflammation. The pathogenesis of dcm is complex, and increasing oxidative stress caused by disorder of glucose metabolism may be one of the key links of dcm. Given the important roles of ros signaling in both cardiac physiology and disease, ros signaling. Jun 19, 2012 given the central role of oxidative stress in the pathogenesis of diabetes and diabetic cardiomyopathy, there is growing interest in the use of antioxidants as a complementary therapeutic approach.
Hyperglycemiainduced oxidative stress and heart disease. Mitochondrial dysfunction contributes to heart failure in diabetes. Metallothionein suppression of diabetic cardiomyopathy by inhibition of hyperglycemiainduced oxidative stress. Hginduced oxidative stress is a major risk factor for the development of microvascular pathogenesis in the diabetic myocardium, resulting in myocardial cell death, hypertrophy, fibrosis, abnormalities of calcium homeostasis and endothelial dysfunction. Cannabidiol attenuates cardiac dysfunction, oxidative stress. Diabetes has emerged as a major threat to worldwide health. Objectives diabetic patients are known to have an independent risk of cardiomyopathy. Cichorium intybus attenuates streptozotocin induced diabetic. Given the central role of oxidative stress in the pathogenesis of diabetes and diabetic cardiomyopathy, there is growing interest in the use of antioxidants as a complementary therapeutic approach. Antioxidants, apoptosis, curcumin, diabetic cardiomyopathy, edaravone, fibrosis, hypertrophy, oxidative stress, resveratrol, tempol. Background cannabidiol, the most abundant nonpsychoactive constituent of cannabis sativa marijuana plant, exerts anti. Hfpef heart failure with preserved ventricular function.
Under normal conditions, nrf2 is bound to kelchlike echassociated protein 1 keap1 in the cytoplasm. Oxidative stress and diabetic complications circulation. Phloretin phl, a promising natural product, has many pharmacological activities, such as antiinflammatory, anticancer, and anti oxidative function. These pathogenic changes may contribute to compromised ventricular dysfunction in diabetes, which is one of the leading causes of death in the world today. Such subcellular remodeling plays a critical role in the pathogenesis of diabetic cardiomyopathy.
Apr 25, 2007 oxidative stress and diabetic cardiomyopathy oxidative stress and diabetic cardiomyopathy cai, lu. Request pdf diabetic cardiomyopathy and oxidative stress diabetes mellitus dm is the most common metabolic disorder associated with high mortality, which is mostly due to its cardiovascular. Tetrahydrocurcumin ameliorates diabetic cardiomyopathy by. Role of differential signaling pathways and oxidative stress in diabetic cardiomyopathy. Role of differential signaling pathways and oxidative stress. This has been confirmed by various laboratory studies showing strong correlation between oxidative. Diabetic cardiomyopathy is a type of cardiovascular damage present in diabetes patients. In this study, we explored the role of cb1 receptors in myocardial dysfunction, inflammation, oxidativenitrative stress, cell death, and interrelated signaling pathways, using a mouse model of type 1 diabetic cardiomyopathy. Treatment aimed at these processes may be beneficial in dcm. However, hyperglycemia, as an independent risk factor, directly. Oxidative stress, in the diabetic heart, playas a key role in the development and progression of diabetic cardiomyopathy. Therapeutic interventions to prevent calcium accumulation and oxidative stress could be therefore helpful in improving the cardiac function under diabetic. Attenuation by metallothionein of early cardiac cell death. It is unclear if these changes are adaptive or maladaptive.
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