Diptarka Ray - Academia.edu (original) (raw)

Papers by Diptarka Ray

Circulation, 2008

Glutaredoxin-1 [Grx1], a redox regulator of thioredoxin superfamily has been implicated in myocar... more Glutaredoxin-1 [Grx1], a redox regulator of thioredoxin superfamily has been implicated in myocardial ischemia reperfusion injury. Diabetes is a well-recognized cardiovascular risk factor. Grx1 has been shown to protect the heart from ischemia reperfusion induced injuries. The present study examined whether Grx1 gene therapy could render the diabetic hearts resistant to ischemia reperfusion injury. Diabetes was induced with streptozotocin, and after the diabetes was confirmed, male C57B1/J6 mice were assigned to one of the two groups and open heart surgery was performed. The mice received an intra-myocardial injection of 109 p.f.u. adenovirus encoding Grx1 or injected with empty vector or adenovirus with LacZ. Three days later, the animals were sacrificed and isolated hearts were subjected to 30 min ischemia followed by 2 hours of reperfusion. Ventricular function was examined, and myocardial infarct size and cardiomyocyte apoptosis were determined. Hemodynamic parameters of the Grx...

Food & Function, 2019

Correction for ‘Protective role of air potato (Dioscorea bulbifera) of yam family in myocardial i... more Correction for ‘Protective role of air potato (Dioscorea bulbifera) of yam family in myocardial ischemic reperfusion injury’ by Hannah Rachel Vasanthi et al., Food Funct., 2010, 1, 278–283.

Journal of Cellular and Molecular Medicine, 2011

The major problem in stem cell therapy includes viability and engraftment efficacy of stem cells ... more The major problem in stem cell therapy includes viability and engraftment efficacy of stem cells after transplantation. Indeed, the vast majority of host-transfused cells do not survive beyond 24-72 hrs. To increase the survival and engraftment of implanted cardiac stem cells in the host, we developed a technique of treating these cells with resveratrol, and tested it in a rat model of left anterior descending (LAD) occlusion. Multi-potent clonogenic cardiac stem cells isolated from rat heart and stably transfected with EGFP were pre-treated with 2.5 M resveratrol for 60 min. Rats were anaesthetized, hearts opened and the LAD occluded to induce heart attack. One week later, the cardiac reduced environment was confirmed in resveratrol treated rat hearts by the enhanced expression of nuclear factor-E2related factor-2 (Nrf2) and redox effector factor-1 (Ref-1). M-mode echocardiography after stem cell therapy, showed improvement in cardiac function (left ventricular ejection fraction, fractional shortening and cardiac output) in both, the treated and control group after 7 days, but only resveratrol-modified stem cell group revealed improvement in cardiac function at the end of 1, 2 and 4 months time. The improvement of cardiac function was accompanied by enhanced stem cell survival and engraftment as demonstrated by the expression of cell proliferation marker Ki67 and differentiation of stem cells towards the regeneration of the myocardium as demonstrated by the expression of EGFP up to 4 months after LAD occlusion in the resveratrol-treated stem cell group. Expression of stromal cell-derived factor and myosin conclusively demonstrated homing of stem cells in the infarcted myocardium, its regeneration leading to improvement of cardiac function.

Food & Function, 2010

Cardioprotective activity of tubers of Dioscorea bulbifera is mediated by inhibition of cardiomyo... more Cardioprotective activity of tubers of Dioscorea bulbifera is mediated by inhibition of cardiomyocyte necrosis and apoptosis as evidenced by the ventricular function and the pro and antiapoptotic protein expression.

Canadian Journal of Physiology and Pharmacology, 2010

Although resveratrol has been proven to possess diverse health benefits, several recent reports h... more Although resveratrol has been proven to possess diverse health benefits, several recent reports have demonstrated conflicting results on some aspects of its effects, including its anti-aging properties. Considerable debate appears to exist on the dose and bioavailability of resveratrol, leading to the controversies on its effectiveness. To resolve the problem, we designed a study with a resveratrol formulation that contained resveratrol supplemented with 5% quercetin and 5% rice bran phytate (commercially known as Longevinex). These ingredients were micronized to increase the bioavailability. Sprague–Dawley rats were gavaged with either Longevinex or vehicle (5% quercetin plus 5% rice bran phytate), and rats were sacrificed after 1 or 3 months, when isolated working hearts were subjected to 30 min ischemia followed by 2 h of reperfusion. Longevinex-treated hearts, irrespective of the duration of treatments, revealed superior cardiac performance, reduced infarct size, and induction o...

Current Pharmaceutical Biotechnology, 2010

Calendula officinalis of family Asteraceae, also known as marigold, has been widely used from tim... more Calendula officinalis of family Asteraceae, also known as marigold, has been widely used from time immemorial in Indian and Arabic cultures as an anti-inflammatory agent to treat minor skin wound and infections, burns, bee stings, sunburn and cancer. At a relatively high dose, calendula can lower blood pressure and cholesterol. Since inflammatory responses are behind many cardiac diseases, we sought to evaluate if calendula could be cardioprotective against ischemic heart disease Two groups of hearts were used: the treated rat hearts were perfused with calendula solution at 50 mM in KHB buffer (in mM: sodium chloride 118, potassium chloride 4.7, calcium chloride 1.7, sodium bicarbonate 25, potassium biphosphate 0.36, magnesium sulfate 1.2, and glucose 10) for 15 min prior to subjecting the heart to ischemia, while the control group was perfused with the buffer only. Calendula achieved cardioprotection by stimulating left ventricular developed pressure and aortic flow as well as by reducing myocardial infarct size and cardiomyocyte apoptosis. Cardioprotection appears to be achieved by changing ischemia reperfusion-mediated death signal into a survival signal by modulating antioxidant and anti-inflammatory pathways as evidenced by the activation of Akt and Bcl2 and depression of TNFα. The results further strengthen the concept of using natural products in degeneration diseases like ischemic heart disease.

Cardiovascular Research, 2009

On the basis of our previous reports that cardioprotection induced by ischaemic preconditioning i... more On the basis of our previous reports that cardioprotection induced by ischaemic preconditioning induces autophagy and that resveratrol, a polyphenolic antioxidant present in grapes and red wine induces preconditioning-like effects, we sought to determine if resveratrol could induce autophagy.

Genes and Nutrition, 2010

A mild-to-moderate wine drinking has been linked with reduced cardiovascular, cerebrovascular, an... more A mild-to-moderate wine drinking has been linked with reduced cardiovascular, cerebrovascular, and peripheral vascular risk as well as reduced risk due to cancer. The reduced risk of cardiovascular disease associated with wine drinking is popularly known as French Paradox. A large number of reports exist in the literature indicating that resveratrol present in wine is primarily responsible for the cardioprotection associated with wine. Recently, resveratrol was shown to extend life span in yeast through the activation of longevity gene SirT1, which is also responsible for the longevity mediated by calorie restriction. This review summarizes the reports available on the functional and molecular biological aspects of resveratrol, wine and grapes in potentiating the longevity genes.

Journal of Cellular and Molecular Medicine, 2010

• Introduction• Stem cell therapy• Regeneration of myocardium 28 days after myocardial infarction... more • Introduction• Stem cell therapy• Regeneration of myocardium 28 days after myocardial infarction• Concluding remarksIntroductionStem cell therapyRegeneration of myocardium 28 days after myocardial infarctionConcluding remarksTo study the efficiency of maintaining the reduced tissue environment via pre-treatment with natural antioxidant resveratrol in stem cell therapy, we pre-treated male Sprague-Dawley rats with resveratrol (2.5 mg/kg/day gavaged for 2 weeks). After occlusion of the left anterior descending coronary artery (LAD), adult cardiac stem cells stably expressing EGFP were injected into the border zone of the myocardium. One week after the LAD occlusion, the cardiac reduced environment was confirmed in resveratrol-treated rat hearts by the enhanced expression of nuclear factor-E2-related factor-2 (Nrf2) and redox effector factor-1 (Ref-1). In concert, cardiac functional parameters (left ventricular ejection fraction and fractional shortening) were significantly improved. The improvement of cardiac function was accompanied by the enhanced stem cell survival and proliferation as demonstrated by the expression of cell proliferation marker Ki67 and differentiation of stem cells towards the regeneration of the myocardium as demonstrated by the enhanced expression of EGFP 28 days after LAD occlusion in the resveratrol-treated hearts. Our results demonstrate that resveratrol maintained a reduced tissue environment by overexpressing Nrf2 and Ref-1 in rats resulting in an enhancement of the cardiac regeneration of the adult cardiac stem cells as demonstrated by increased cell survival and differentiation leading to cardiac function.

Antioxidants & Redox Signaling, 2009

Reactive oxygen species (ROS) are the key mediators of pathogenesis in cardiovascular diseases. M... more Reactive oxygen species (ROS) are the key mediators of pathogenesis in cardiovascular diseases. Members of the thioredoxin superfamily take an active part in scavenging reactive oxygen species, thus playing an essential role in maintaining the intracellular redox status. The alteration in the expression levels of thioredoxin family members and related molecules constitute effective biomarkers in various diseases, including cardiovascular complications that involve oxidative stress. Thioredoxin, glutaredoxin, peroxiredoxin, and glutathione peroxidase, along with their isoforms, are involved in interaction with the members of metabolic and signaling pathways, thus making them attractive targets for clinical intervention. Studies with cells and transgenic animals have supported this notion and raised the hope for possible gene therapy as modern genetic medicine. Of all the molecules, thioredoxins, glutaredoxins, and peroxiredoxins are emphasized, because a growing body of evidence reveals their essential and regulatory role in several steps of redox regulation. In this review, we discuss some pertinent observations regarding their distribution, structure, functions, and interactions with the several survival-and death-signaling pathways, especially in the myocardium. Antioxid. Redox Signal. 11, 2741-2758.

British Journal of Nutrition, 2010

Recently, broccoli, a vegetable of the Brassica family, has been found to protect the myocardium ... more Recently, broccoli, a vegetable of the Brassica family, has been found to protect the myocardium from ischaemic reperfusion injury through the redox signalling of sulphoraphane, which is being formed from glucosinolate present in this vegetable. Since cooked broccoli loses most of its glucosinolate, we assumed that fresh broccoli could be a superior cardioprotective agent compared to cooked broccoli. To test this, two groups of rats were fed with fresh (steamed) broccoli or cooked broccoli for 30 d, while a third group was given vehicle only for the same period of time. After 30 d, all the rats were sacrificed, and the isolated working hearts were subjected to 30 min ischaemia followed by 2 h of reperfusion. Both cooked and steamed broccolis displayed significantly improved post-ischaemic ventricular function and reduced myocardial infarction and cardiomyocyte apoptosis compared to control, but steamed broccoli showed superior cardioprotective abilities compared with the cooked broccoli. Corroborating with these results, both cooked and steamed broccolis demonstrated significantly enhanced induction of the survival signalling proteins including Bcl2, Akt, extracellular signal-regulated kinase 1/2, haemoxygenase-1, NFE2 related factor 2, superoxide dismutase (SOD1) and SOD2 and down-regulation of the proteins (e.g. Bax, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase) of the death signalling pathway, steamed broccoli displaying superior results over its cooked counterpart. The expressions of proteins of the thioredoxin (Trx) superfamily including Trx1 and its precursor sulphoraphane, Trx2 and Trx reductase, were enhanced only in the steamed broccoli group. The results of the present study documented superior cardioprotective properties of the steamed broccoli over cooked broccoli because of the ability of fresh broccoli to perform redox signalling of Trx.

Journal of Cardiovascular Pharmacology, 2009

Borreria hispida (BHE), a weed of Rubiaceae family, is being used from time immemorial as an alte... more Borreria hispida (BHE), a weed of Rubiaceae family, is being used from time immemorial as an alternative therapy for diabetes. To evaluate the scientific background of using BHE as therapy to reduce cardiovascular risk, a group of rats were given BHE for a period of 30 days, whereas control animals were given the vehicle only. The animals were sacrificed, the hearts were isolated, and perfused with buffer. All the hearts were subjected to 30-minute ischemia followed by 2-hour reperfusion. Compared with vehicle-treated rats, BHE-treated rat hearts showed improved post-ischemic ventricular function and exhibited reduced myocardial infarct size and cardiomyocyte apoptosis. The level of cytochrome c expression and caspase 3 activation was also reduced. BHE elevated antiapoptotic proteins Bcl-2 and heme oxygenase-1 and stimulated the phosphorylation of survival protein Akt simultaneously decreasing the apoptotic proteins Bax and Src. In addition, BHE enhanced the protein expression of peroxisome proliferator-activated receptor-gamma, peroxisome proliferator-activated receptor-delta, and Glut-4, probably revealing the antiobese and antidiabetic potential of BHE. These results indicate that treatment with BHE improves cardiac function and ameliorates various risk factors associated with cardiac disease, suggesting that BHE can be considered as a potential plant-based nutraceutical and pharmaceutical agent for the management of cardiovascular diseases.

Heart Failure Reviews, 2011

Resveratrol, a polyphenol phytoalexin, present in red wine and grapes possesses diverse biochemic... more Resveratrol, a polyphenol phytoalexin, present in red wine and grapes possesses diverse biochemical and physiological properties, including estrogenic, antiplatelet, and anti-inflammatory properties as well as a wide range of health benefits ranging from chemoprevention to cardioprotection. Recently, several studies described resveratrol as an anti-aging compound. This review focuses on the anti-aging aspects of resveratrol, the possible mechanisms of action, and emerging controversy on its life-prolonging ability. It appears that resveratrol can induce the expression of several longevity genes including Sirt1, Sirt3, Sirt4, FoxO1, Foxo3a and PBEF and prevent aging-related decline in cardiovascular function including cholesterol level and inflammatory response, but it is unable to affect actual survival or life span of mice.

Canadian Journal of Physiology and Pharmacology, 2009

A growing body of evidence supports the role of redox signaling in the mechanisms of hematopoieti... more A growing body of evidence supports the role of redox signaling in the mechanisms of hematopoietic stem cell mobilization and homing. Cytokines and adhesion molecules control stem cell mobilization through a redox-regulated process. The FoxO-SirT network appears to be intimately involved in redox-regulated stem cell homeostasis, whereas the process of stem cell differentiation is regulated by redox effector factor-1 (Ref-1) protein. Lack of oxygen (hypoxia), specifically controlled hypoxia, can stimulate the growth of the stem cells in their niche, and hypoxia-inducible factor (HIF)-1alpha appears to play a significant role in their maintenance and homing mechanism.

Journal of Natural Products, 2009

A study was undertaken to determine the cardioprotective effects of parrodienes prepared from the... more A study was undertaken to determine the cardioprotective effects of parrodienes prepared from the feather pigments of parrots (Ara macao). Adult male Sprague-Dawley rats were divided into three experimental groups and perfused with KHB buffer with or without treatment of 2,4,6-octatrienal (1) (50 mM) or its potassium salt (2) (50 mM). All hearts were then subjected to 30 min ischemia followed by a 2 h reperfusion. Ischemia/reperfusion resulted in a significant amount of tissue injury, cardiomyocyte apoptosis, and depression in hemodynamic functions. Parrodiene treatment prevented the development of myocardial injury after ischemia/reperfusion. Western blot analysis indicated that 1 and 2 reduced the oxidative stress, induced the expression of Bcl-2, and caused increased phosphorylation of Akt. These agents also reduced myocardial ischemic reperfusion injury presumably by reducing oxidative stress and activating the survival signal through the Akt-Bcl-2 pathway.

Febs Letters, 2010

Keywords: Hexim1 Cardiac lineage protein-1 Redox factor Ischemia-reperfusion Cardiac Ref-1 Nuclea... more Keywords: Hexim1 Cardiac lineage protein-1 Redox factor Ischemia-reperfusion Cardiac Ref-1 Nuclear factor erythroid 2-related factor Thioredoxin a b s t r a c t CLP-1, the mouse homologue of human Hexim1 protein, exerts inhibitory control on transcriptional elongation factor-b of RNA transcript elongation. Previously, we have demonstrated that downregulation of cardiac lineage protein-1 (CLP-1) in CLP-1 +/À heterozygous mice affords cardioprotection against ischemia-reperfusion injury. Our current study results show that the improvement in cardiac function in CLP-1 +/À mice after ischemia-reperfusion injury is achieved through the potentiation of redox signaling and their molecular targets including redox effector factor-1, nuclear factor erythroid 2-related factor, and NADPH oxidase 4 and the active usage of thioredoxin-1, thioredoxin-2, glutaredoxin-1 and glutaredoxin-2. Our results suggest that drugs designed to down regulate CLP-1 could confer cardioprotection through the potentiation of redox cycling.

Heart Failure Reviews, 2010

Journal of Cellular and Molecular Medicine, 2009

This study compared two dietary phytochemicals, grape-derived resveratrol and palm oil-derived γ-... more This study compared two dietary phytochemicals, grape-derived resveratrol and palm oil-derived γ-tocotrienol, either alone or in combination, on the contribution of autophagy in cardioprotection during ischaemia and reperfusion. Sprague-Dawley rats weighing between 250 and 300 g were randomly assigned to one of the following groups: vehicle, ischaemia/reperfusion (I/R), resveratrol + I/R, γ-tocotrienol + I/R, resveratrol +γ-tocotrienol + I/R. For resveratrol treatments, the rats were gavaged with resveratrol (2.5 mg/kg) for 15 days while for γ-tocotrienol experiments the rats were gavaged with γ-tocotrienol (0.3 mg/kg) for 30 days. For the combined resveratrol +γ-tocotrienol experiments, the rats were gavaged with γ-tocotrienol for 15 days, and then gavaging continued with resveratrol along with γ-tocotrienol for a further period of 15 days. After 30 days, isolated perfused hearts were subjected to 30 min. of global ischaemia followed by 2 hrs of reperfusion. Our results showed for the first time that at least in part, the cardioprotection (evidenced from the ventricular performance, myocardial infarct size and cardiomyocyte apoptosis) with resveratrol and γ-toctrienol was achieved by their abilities to induce autophagy. Most importantly, resveratrol and γ-tocotrienol acted synergistically providing greater degree of cardioprotection simultaneously generating greater amount of survival signal through the activation of Akt-Bcl-2 survival pathway. Autophagy was accompanied by the activation of Beclin and LC3-II as well as mTOR signalling, which were inhibited by either 3-methyl adenine (3-MA) or Wortmannin. The autophagy was confirmed from the results of transmission electron microscopy and light microscopy as well as with confocal microscopy. It is tempting to speculate that during ischaemia and reperfusion autophagy along with enhanced survival signals helps to recover the cells from injury.