Dharamvir Singh Arya

All India Institute of Medical Sciences, New Dilli, NCT, India

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Publications (57)111.92 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Impaired glucose metabolism either in prediabetes or diabetes mellitus is one of the detrimental root causes of premature mortality throughout the world. Uncontrolled prediabetes coincides with the induction of diabetic mellitus and associated cardiovascular diseases (CVDs). Needless to mention, impaired glucose metabolism, including impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), have been known individually or in combination as the prediabetic stage but by itself it is not diabetes mellitus. Impaired β-cell function, insulin resistance, increased level of free fatty acids, hyperinsulinemia and down-regulation of GLUT-4 are critical impairments during prediabetes. The vascular endothelium sustains the free flow of blood in vessels by normalizing vascular tone by releasing numerous endothelial-derived factors. However, in recent studies a marked impairment in endothelial-derived factors has been observed in prediabetes. Thus, the impaired endothelial-derived factors could make prediabetic patients more vulnerable to cardiovascular disease pathology. Nobel laureates, Robert Furchgott, Louis Ignarro and Ferid Murad (1998) discovered a novel signalling molecule, nitric oxide (NO), identified as an endothelium-derived relaxing factor. This imperative mediator has potent vasodilatory, anti-platelet, anti-proliferative, and anti-inflammatory actions in vessels. Endothelium-derived NO generation is mediated through the activation of PI3-K-Akt-eNOS-NO signalling pathways. Therefore, conspicuous destruction in PI3-K-Akt-eNOS-NO signalling has been revealed in prediabetes and renders individuals more susceptible to CVDs. Several research reports have defined prediabetes as a platform for diabetes mellitus and associated CVDs. But the molecular alteration during prediabetes is unclear; however, the signalling modulator may be an imperative issue and may open a prerequisite new vista for novel research. In this review, we have critically discussed the possible signalling alteration in prediabetes.
    RSC Advances 11/2014; 5(2):1619. · 3.71 Impact Factor
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    ABSTRACT: Hesperidin has been shown to possess cardioprotective and anti-diabetic potential. Hitherto, its molecular mechanism on isoproterenol (ISO)-induced myocardial dysfunction in diabetes is still not explored. Hence, for the first time we sought to investigate whether hesperidin exerts any beneficial effect on the pathophysiology of myocardial infarction (MI) in diabetes through the PPAR-γ pathway by assessing a variety of indices e.g., apoptosis, hemodynamic, biochemical and histoarchitectural changes. Diabetes was induced by a single dose of STZ (50 mg/kg IP). Diabetic rats received either hesperidin (100 mg/kg/day orally), the PPAR-γ antagonist GW9662 (1 mg/kg/day IP), or both for 14 days with concurrent administration of ISO (85 mg/kg SC) on days 13 and 14. ISO-STZ rats resulted in severe myocardial dysfunction (decreased ±LVdP/dt and increased LVEDP). In addition, augmented myocardial thiobarbituric acid-reactive substances and serum troponin-I with a concomitant decrease in level of glutathione and activities of catalase, superoxide dismutase antioxidants with cardiac injury biomarkers creatine kinase-MB isoenzyme, lactate dehydrogenase were seen. Morphological studies of the ISO-STZ challenged myocardium exhibited severe necrosis, edema and inflammatory changes. In western blot analysis, Bcl-2 and PPAR-γ expression were decreased where as Bax expression was significantly increased, suggesting role of apoptosis in myocardial dysfunction. Interestingly, hesperidin treatment positively modulated these parameters as validated by improved hemodynamic and left ventricular functions, fortified endogenous anti-oxidant defence system and improved structural integrity of the myocardium. However, significant effects were lowered in animals treated with hesperidin plus GW9662. Moreover, down-regulated PPAR-γ and Bcl-2 expressions in myocardial infarcted diabetic hearts were increased by hesperidin treatment. Hence, for the first time the present study suggests that, hesperidin reduces oxidative stress, apoptosis and improves cardiac function via the PPAR-γ pathway.
    Chemico-biological interactions. 06/2014;
  • Jagriti Bhatia, Nanda Gamad, Saurabh Bharti, Dharamvir Singh Arya
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    ABSTRACT: Canagliflozin (CFZ) is a member of new class of glucose lowering agents, sodium-glucose co-transporter (SGLT) inhibitors, which got approval by food and drug administration. It has insulin independent action by blocking the transporter protein SGLT2 in the kidneys, resulting in urinary glucose excretion and reduction in blood glucose levels. In clinical trials, CFZ significantly decreased HbA1c level when administered either as monotherapy or as combined therapy with other anti-diabetic drugs. Intriguingly, it showed additional benefits like weight reduction and lowering of blood pressure. The commonly observed side effects were urinary and genital infections. It has exhibited favorable pharmacokinetic and pharmacodynamic profiles even in patients with renal and hepatic damage. Hence, this review purports to outline CFZ as a newer beneficial drug for type 2 diabetes mellitus.
    World journal of diabetes. 06/2014; 5(3):399-406.
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    ABSTRACT: Naringin, chemically 4',5,7- trihydroxyflavanone-7-rhamnoglucoside, is a major flavanone glycoside obtained from tomatoes, grapefruits, and many other citrus fruits. It has been experimentally documented to possess numerous biological properties such as antioxidant, anti-inflammatory, and antiapoptotic activities. In vitro and in vivo studies have further established the usefulness of naringin in various preclinical models of atherosclerosis, cardiovascular disorders, diabetes mellitus, neurodegenerative disorders, osteoporosis, and rheumatological disorders. Apart from this, naringin has also exerted chemopreventive and anticancer attributes in various models of oral, breast, colon, liver, lung, and ovarian cancer. This wide spectrum of biological expediency has been documented to be a result of either the upregulation of various cell survival proteins or the inhibition of inflammatory processes, or a combination of both. Due to the scarcity of human studies on naringin, this review focuses on the various established activities of naringin in in vitro and in vivo preclinical models, and its potential therapeutic applications using the available knowledge in the literature. Additionally, it also encompasses the pharmacokinetic properties of naringin and its inhibition of CYP isoenzymes, and the subsequent drug interactions. Moreover, further clinical research is evidently needed to provide significant insights into the mechanisms underlying the effects of naringin in humans.
    Planta Medica 04/2014; · 2.35 Impact Factor
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    ABSTRACT: The present study investigated the effect of hesperidin, a natural flavonoid, in cardiac ischemia and reperfusion (I/R) injury in diabetic rats. Male Wistar rats with diabetes were divided into five groups and were orally administered saline once daily (IR-sham and IR-control), Hesperidin (100 mg/kg/day; IR-Hesperidin), GW9962 (PPAR-γ receptor antagonist), or combination of both for 14 days. On the 15th day, in the IR-control and IR-treatment groups, rats were subjected to left anterior descending (LAD) coronary artery occlusion for 45 minutes followed by a one-hour reperfusion. Haemodynamic parameters were recorded and rats were sacrificed; hearts were isolated for biochemical, histopathological, ultrastructural and immunohistochemistry. In the IR-control group, significant ventricular dysfunctions were observed along with enhanced expression of pro-apoptotic protein Bax. A decline in cardiac injury markers lactate dehydrogenase activity, CK-MB and increased content of thiobarbituric acid reactive substances, a marker of lipid peroxidation, and TNF-α were observed. Hesperidin pretreatment significantly improved mean arterial pressure, reduced left ventricular end-diastolic pressure, and improved both inotropic and lusitropic function of the heart (+LVdP/dt and -LVdP/dt) as compared to IR-control. Furthermore, hesperidin treatment significantly decreased the level of thiobarbituric acid reactive substances and reversed the activity of lactate dehydrogenase towards normal value. Hesperidin showed anti-apoptotic effects by upregulating Bcl-2 protein and decreasing Bax protein expression. Additionally, histopathological and ultrastructural studies reconfirmed the protective action of hesperidin. On the other hand, GW9662, selective PPAR-γ receptor antagonist, produced opposite effects and attenuated the hesperidin induced improvements. The study for the first time evidence the involvement of PPAR-γ pathway in the cardioprotective activity of hesperidin in I/R model in rats.
    PLoS ONE 01/2014; 9(11):e111212. · 3.53 Impact Factor
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    ABSTRACT: Normal rats pre-treated with P. kurroa (200 mg/kg) alone did not showed significant change, however, isoproterenol (ISP) administration resulted in hemodynamic and left ventricular dysfunction, oxidative stress, and lipid peroxidation. Such cardiac dysfunction was significantly prevented by P. kurroa root extract pre-treatment. Pre-treatment significantly attenuated the ISP-induced oxidative stress by restoring myocardial superoxide dismutase, catalase, and glutathione peroxidase enzymes except reduced glutathione content. P. kurroa pre-treatment markedly attenuated the ISP-induced rise in lipid peroxidation, thereby prevented leakage of myocyte creatine kinase-MB and lactate dehydrogenase enzymes. The results suggest that P. kurroa root extract possesses significant cardioprotective effect, which may be attributed to its antioxidant, anti-peroxidative, and myocardial preservative properties.
    Indian journal of experimental biology 09/2013; 51(9):694-701. · 1.20 Impact Factor
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    ABSTRACT: The present study examined the effects of licorice on antioxidant defense, functional impairment, histopathology, and ultrastructural alterations in isoproterenol (ISP)-induced myocardial injury in rats. Myocardial necrosis was induced by two subcutaneous injection of ISP (85 mg/kg) at an interval of 24 h. Licorice was administered orally for 30 days in the doses of 100, 200, 400, or 800 mg/kg. ISP-treated rats showed impaired hemodynamics, left ventricular dysfunction, and caused depletion of antioxidants and marker enzymes along with lipid peroxidation from myocardium. ISP also induced histopathological and ultrastructural alterations in myocardium. Pretreatment with licorice prevented the depletion of endogenous antioxidants and myocyte injury marker enzymes, inhibited lipid peroxidation, and showed recovery of hemodynamic and ventricular functions. Licorice treatment also reduced myonecrosis, edema, and infiltration of inflammatory cells and showed preservation of subcellular and ultrastructural components. Our results demonstrate that licorice exerts cardioprotection by reducing oxidative stress, augmenting endogenous antioxidants, and restoring functional parameters as well as maintaining structural integrity.
    Toxicology and Industrial Health 06/2013; · 1.56 Impact Factor
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    ABSTRACT: Naringin has antioxidant properties that could improve redox-sensitive myocardial ischemia reperfusion (IR) injury. This study was designed to investigate whether naringin restores the myocardial damage and dysfunction in vivo after IR and the mechanisms underlying its cardioprotective effects. Naringin (20-80 mg/kg/day, p.o.) or saline were administered to rats for 14 days and the myocardial IR injury was induced on 15(th) day by occluding the left anterior descending coronary artery for 45 min and subsequent reperfusion for 60 min. Post-IR rats exhibited pronounced cardiac dysfunction as evidenced by significantly decreased mean arterial pressure, heart rate, +LVdP/dt max (inotropic state), -LVdP/dt max (lusitropic state) and increased left ventricular end diastolic pressure as compared to sham group, which was improved by naringin. Further, on histopathological and ultrastructural assessments myocardium and myocytes appeared more normal in structure and the infarct size was reduced significantly in naringin 40 and 80 mg/kg/day group. This amelioration of post-IR-associated cardiac injury by naringin was accompanied by increased nitric oxide (NO) bioavailability, decreased NO inactivation to nitrotyrosine, amplified protein expressions of Hsp27, Hsp70, β-catenin and increased p-eNOS/eNOS, p-Akt/Akt, and p-ERK/ERK ratio. In addition, IR-induced TNF-α/IKK-β/NF-κB upregulation and JNK phosphorylation were significantly attenuated by naringin. Moreover, western blotting and immunohistochemistry analysis of apoptotic signaling pathway further established naringin cardioprotective potential as it upregulated Bcl-2 expression and downregulated Bax and Caspase-3 expression with reduced TUNEL positivity. Naringin also normalized the cardiac injury markers (lactate dehydrogenase and creatine kinase-MB), endogenous antioxidant activities (superoxide dismutase, reduced glutathione and glutathione peroxidase) and lipid peroxidation levels. Thus, naringin restored IR injury by preserving myocardial structural integrity and regulating Hsp27, Hsp70, p-eNOS/p-Akt/p-ERK signaling and inflammatory response.
    PLoS ONE 01/2013; 8(12):e82577. · 3.53 Impact Factor
  • Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie 11/2012; · 1.43 Impact Factor
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    ABSTRACT: Hepatocellular apoptosis is an essential pathological feature of alcoholic liver disease. Adiponectin, an adipokine predominantly secreted from adipose tissue, has been shown to play beneficial roles in alcoholic liver disease against various inflammatory and pro-apoptotic molecules. However, the effects of adiponectin on ethanol-induced apoptosis in liver cells are largely unknown. Herein, we investigated the role of globular adiponectin (gAcrp) in the prevention of ethanol-induced apoptosis and further tried to decipher the potential mechanisms involved. In the present study, we demonstrated that gAcrp significantly inhibits both ethanol-induced increase in Fas ligand expression and activation of caspase-3 in human hepatoma cell lines (HepG2 cells), suggesting that gAcrp plays a protective role against ethanol-induced apoptosis in liver cells. This protective effect of gAcrp was mediated through adiponectin receptor R1 (adipoR1). Further, globular adiponectin treatment caused induction of heme oxygenase-1 (HO-1) through, at least in part, nuclear factor (erythroid-derived 2)-like 2, (Nrf2) signaling. Treatment with SnPP, a pharmacological inhibitor of HO-1, and knockdown of HO-1 with small interfering RNA (siRNA) restored caspase-3 activity suppressed by gAcrp, indicating a critical role of HO-1 in mediating the protective role of gAcrp in ethanol-induced apoptosis in liver cells. In addition, carbon monoxide, a byproduct obtained from the catabolism of free heme was found to contribute to the anti-apoptotic effect of adiponectin. In conclusion, these data demonstrated that globular adiponectin prevents ethanol-induced apoptosis in HepG2 cells via HO-1 induction and revealed a novel biological response of globular adiponectin in the protection of liver injury from alcohol consumption.
    Biochemical pharmacology 07/2012; 84(7):974-83. · 4.25 Impact Factor
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    ABSTRACT: Syzygium cumini (SC) is well known for its anti-diabetic potential, but the mechanism underlying its amelioration of type 2 diabetes is still elusive. Therefore, for the first time, we investigated whether SC aqueous seed extract (100, 200, or 400 mg/kg) exerts any beneficial effects on insulin resistance (IR), serum lipid profile, antioxidant status, and/or pancreatic β-cell damage in high-fat diet / streptozotocin-induced (HFD-STZ) diabetic rats. Wistar albino rats were fed with HFD (55% of calories as fat) during the experiment to induce IR and on the 10th day were injected with STZ (40 mg/kg, i.p.) to develop type 2 diabetes. Subsequently, after confirmation of hyperglycemia on the 14th day (fasting glucose level > 13.89 mM), diabetic rats were treated with SC for the next 21 days. Diabetic rats showed increased serum glucose, insulin, IR, TNF-α, dyslipidemia, and pancreatic thiobarbituric acid-reactive substances with a concomitant decrease in β-cell function and pancreatic superoxide dismutase, catalase, and glutathione peroxidase antioxidant enzyme activities. Microscopic examination of their pancreas revealed pathological changes in islets and β-cells. These alterations reverted to near-normal levels after treatment with SC at 400 mg/kg. Moreover, hepatic tissue demonstrated increased PPARγ and PPARα protein expressions. Thus, our study demonstrated the beneficial effect of SC seed extract on IR and β-cell dysfunction in HFD-STZ-induced type 2 diabetic rats.
    Journal of Pharmacological Sciences 06/2012; 119(3):205-13. · 2.15 Impact Factor
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    FEBS Letters. 06/2012; 586(13):1832.
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    ABSTRACT: This article has been withdrawn at the request of the editors. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
    Biochimica et Biophysica Acta 05/2012; · 4.66 Impact Factor
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    ABSTRACT: Increased oxidative stress and inflammation in obesity are the central and causal components in the pathogenesis and progression of cardiometabolic syndrome (CMetS). The aim of the study was to determine the potential role of sesamol (a natural powerful antioxidant and anti-inflammatory phenol derivative of sesame oil) in chronic high-cholesterol/high-fat diet (HFD)-induced CMetS in rats and to explore the molecular mechanism driving this activity. Rats were fed with HFD (55% calorie from fat and 2% cholesterol) for 60 days to induce obesity, dyslipidemia, insulin resistance (IR), hepatic steatosis and hypertension. On the 30th day, rats with total cholesterol >150 mg/dl were considered hypercholesterolemic and administered sesamol 2, 4 and 8 mg/kg per day for the next 30 days. Sesamol treatment decreased IR, hyperinsulinemia, hyperglycemia, dyslipidemia, TNF-α, IL-6, leptin, resistin, highly sensitive C-reactive protein (hs-CRP), hepatic transaminases and alkaline phosphatase, along with normalization of adiponectin, nitric oxide and arterial pressures in a dose-dependent fashion. Increased TBARS, nitrotyrosine and decreased antioxidant enzyme activities were also amended in HFD rats. Similarly, sesamol normalized hepatic steatosis and ultrastructural pathological alteration in hepatocytes, although the effect was more pronounced at 8 mg/kg. Furthermore, hepatic PPARγ, PPARα and e-NOS protein expressions were increased, whereas LXRα, SERBP-1c, P-JNK and NF-κB expression were decreased by sesamol treatment. These results suggest that sesamol attenuates oxidative stress, inflammation, IR, hepatic steatosis and hypertension in HFD-fed rats via modulating PPARγ, NF-κB, P-JNK, PPARα, LXRα, SREBP-1c and e-NOS protein expressions, thereby preventing CMetS. Thus, the present study demonstrates the therapeutic potential of sesamol in alleviating CMetS.
    The Journal of nutritional biochemistry 03/2012; 23(11):1482-9. · 4.29 Impact Factor
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    ABSTRACT: Protecting myocardium from ischaemia-reperfusion (I-R) injury is important to reduce the complication of myocardial infarction (MI) and interventional revascularization procedures. In the present study, the cardioprotective potential of hydroalcoholic extract of Andrographis paniculata was evaluated against left anterior descending coronary artery (LADCA) ligation-induced I-R injury of myocardium in rats. MI was induced in rats by LADCA ligation for 45 min followed by reperfusion for 60 min. The rats were divided into five experimental groups viz., sham (saline treated, but LADCA was not ligated), I-R control (saline treated + I-R), benazepril (30 mg/kg + I-R), A. paniculata (200 mg/kg per se) and A. paniculata (200 mg/kg + I-R). A. paniculata was administered orally for 31 days. On day 31, rats were subjected to the I-R and cardiac function parameters were recorded. Further, rats were sacrificed and heart was excised for biochemical and histopathological studies. In I-R control group, LADCA ligation resulted in significant cardiac dysfunction evidenced by reduced haemodynamic parameters; mean arterial pressure (MAP) and heart rate (HR). The left ventricular contractile function was also altered. In I-R control group, I-R caused decline in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) as well as leakage of myocytes injury marker enzymes, creatine phosphokinase-MB (CK-MB) isoenzyme and lactate dehydrogenase (LDH), and enhanced lipid peroxidation product, malonaldialdehyde (MDA). However, rats pretreated with A. paniculata 200 mg/kg showed favourable modulation of haemodynamic and left ventricular contractile function parameters, restoration of the myocardial antioxidants and prevention of depletion of myocytes injury marker enzymes along with inhibition of lipid peroxidation. Histopathological observations confirmed the protective effects of A. paniculata. The cardioprotective effects of A. paniculata were found comparable to that of benazepril treatment. Interpretation & Our results showed the cardioprotective effects of A. paniculata against I-R injury likely result from the suppression of oxidative stress and preserved histoarchitecture of myofibrils along with improved haemodynamic and ventricular functions.
    The Indian Journal of Medical Research 03/2012; 135:414-21. · 2.06 Impact Factor
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    ABSTRACT: Present study evaluated the cardioprotective effect of Andrographis paniculata (100, 200 or 400 mg/kg) against isoproterenol (85 mg/kg, b.w.)-induced cardiotoxicity referred as myocardial infarction in rats. Isoproterenol significantly (p < 0.05) decreased mean arterial pressure, heart rate, contractility and relaxation and increased left ventricular end diastolic pressure. Isoproterenol also significantly (p < 0.05) decreased antioxidants, superoxide dismutase, catalase, glutathione peroxidase, glutathione and increased leakage of cardiac injury markers; creatine phosphokinase-MB isoenzyme, lactate dehydrogenase concomitant to increased lipid peroxidation and histopathological perturbations. However, pretreatment with A. paniculata favorably restored hemodynamic parameters and left ventricular function and significantly (p < 0.05) prevented the depletion of endogenous antioxidants and myocyte marker enzymes as well as inhibited lipid peroxidation. Significant (p < 0.05) reversal of almost all the hemodynamic, biochemical and histopathological parameters by A. paniculata pretreatment in isoproterenol-induced cardiotoxicity depicted the cardioprotective effect of A. paniculata. Results showed that A. paniculata protected heart against cardiotoxic effects of isoproterenol by boosting endogenous antioxidant network, restoring ventricular function and maintaining structural integrity of heart.
    Acta poloniae pharmaceutica 01/2012; 69(2):269-78. · 0.67 Impact Factor
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    ABSTRACT: Herein, we studied the cross talk between 5-HT(2B) receptor blocker (SB-204741) and GSK-3β inhibitor (SB-216763) in isoproterenol-induced cardiac hypertrophy for 28 days. SB-204741 treatment significantly ameliorated (P<0.05) myocardial dysfunction, myocyte area, fibrosis and myocardial architecture in isoproterenol insulted myocardium. Moreover, this improvement in functional and morphological changes was associated with suppression of hypertrophic (BNP and CK-MB), inflammatory (IKK-β/NF-κB/TNF-α and CRP), and apoptotic markers (TUNEL positivity and Bax expression) along with phosphorylation of Akt/GSK-3β/β-catenin/eNOS. Intriguingly, co-treatment with GSK-3β inhibitor (P<0.01) further amplified the anti-hypertrophic effect of SB-204741 (P<0.05) such that the effect was indistinguishable from that of vehicle treated rats. Thus, 5-HT(2B) receptor blockade mediated anti-hypertrophic effect is atleast in part is governed through phosphorylation of Akt/GSK-3β/β-catenin/eNOS via attenuating inflammatory and apoptotic pathways.
    FEBS letters 12/2011; 586(2):180-5. · 3.54 Impact Factor
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    ABSTRACT: Commiphora mukul commonly known as Guggul is one of the oldest and commonly consumed herb for promoting heart and vascular health. Present study was undertaken to evaluate cardioprotective potential of Commiphora mukul against isoprenaline-induced myocardial necrosis in rats. Wistar albino rats were divided into three main groups: sham (saline only), isoprenaline control (saline and isoprenaline) and Commiphora mukul treated (Commiphora mukul and isoprenaline) groups. Commiphora mukul was administered in three doses 100, 200 and 400 mg kg(-1) p.o. for 30 days. On 29th and 30th day, the animals of isoprenaline control and Commiphora mukulpretreatment groups were administered isoprenaline (85 mg kg(-1); s.c.), consecutively at an interval of 24 hr. Isoprenaline administration produced a significant (p < 0.05) decrease in myocardial antioxidants; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx), reduced glutathione (GSH), and myocyte injury marker enzymes creatine-phosphokinase-MB (CK-MB) and lactate dehydrogenase (LDH) along with enhanced lipid peroxidation; malondialdehyde (MDA) in heart. Commiphora mukul pretreatment reversed the isoprenaline-induced oxidative changes in rat myocardium by significant (p < 0.05) increase in SOD, CAT, GSHPx, GSH and reduction of MDA. In addition to improving myocardial antioxidant status, Commiphora mukul also prevented the leakage of LDH and CK-MB from heart. Further, histopathological examination showed the reduction of necrosis, edema and inflammation following Commiphora mukul pretreatment. Based on present findings, it is concluded that Commiphora mukul may be a potential preventive and therapeutic agent against the oxidative stress associated ischemic heart disease owing to antioxidant and antiperoxidative activity.
    Journal of Environmental Biology 11/2011; 32(6):731-8. · 0.68 Impact Factor
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    ABSTRACT: Emblica officinalis, commonly known as amla, is an important medicinal plant reputed for its dietary and therapeutic uses. The aim of the present study was to investigate the protective role of E. officinalis against isoproterenol (ISP)-induced cardiotoxicity in rats and elucidate the possible mechanism involved. Rats were administered E. officinalis (100, 250 and 500 mg/kg, p.o.) or vehicle (normal saline) for 30 days, with concurrent subcutaneous injections of ISP (85 mg/kg, at 24 h interval) on 29th and 30th day. ISP-induced cardiac dysfunction as evidenced by decreased mean arterial pressure, heart rate, contractility (+LVdP/dt) and relaxation (-LVdP/dt) along with increased left ventricular end diastolic pressure. ISP significantly (p < 0.05) decreased antioxidant enzymes, superoxide dismutase, catalase and glutathione peroxidase and myocyte-injury-specific marker enzymes, creatine phosphokinase-MB and lactate dehydrogenase in heart. A significant (p < 0.05) depletion of reduced glutathione and increase in thiobarbituric acid reactive substances along with histopathological alteration has further indicated the oxidative damage of myocardium. However, pretreatment with E. officinalis exhibited restoration of hemodynamic and left ventricular function along with significant preservation of antioxidants, myocytes-injury-specific marker enzymes and significant inhibition of lipid peroxidation. Furthermore, histopathological salvage of myocardium reconfirmed the protective effects of E. officinalis. Results of the present study demonstrate cardioprotective potential of E. officinalis attributed to its potent antioxidant and free radical scavenging activity as evidenced by favorable improvement in hemodynamic, contractile function and tissue antioxidant status.
    Toxicology and Industrial Health 10/2011; 28(5):399-411. · 1.56 Impact Factor
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    ABSTRACT: Traditional medicine has been appropriately identified as the most productive soil for the cultivation and harvesting of modern medicines. Herein, we postulate that safranal, an active constituent of Crocus sativus, owing to its strong antioxidant and anti-apoptotic potential, could be a valuable molecule in alleviating myocardial ischemia-reperfusion (IR) injury. To evaluate this hypothesis, safranal (0.1-0.5 mL/kg/day, i.p.) or saline were administered to rats for 14 days, and on 15th day, one-stage ligation of left anterior descending coronary artery for 45 min was performed, followed by 60 min reperfusion. We concluded that safranal not only significantly decreased infarct size, but also improved left ventricular functions and the overall hemodynamic status of the myocardium. Interestingly, safranal enhanced phosphorylation of Akt/GSK-3β/eNOS and suppressed IKK-β/NF-κB protein expressions in IR-challenged myocardium. Our findings also imply that safranal exhibits strong anti-apoptotic potential, as evidenced by upregulated Bcl-2 expression and downregulated Bax and caspase3 expression with decreased TUNEL positivity. Moreover, safranal dose-dependently normalized myocardial antioxidant and nitrotyrosine levels, cardiac injury markers (LDH and CK-MB), and decreased TNF-α level in IR-insulted myocardium. Histopathological and ultrastructural findings correlated with the functional and biochemical outcomes showing preserved myocardial architecture and decreased inflammatory cells and edema. Taken together, these results provide convincing evidence of safranal as an invaluable molecule in myocardial IR setting probably due to its fortified antioxidant and anti-apoptotic potential.
    European Journal of Nutrition 10/2011; 51(6):719-27. · 3.13 Impact Factor