Cardiac Marker Enzymes Research Articles

Antioxidant Properties and Cardioprotective Mechanism of Malaysian Propolis in Rats.

Propolis contains high concentrations of polyphenols, flavonoids, tannins, ascorbic acid, and reducing sugars and proteins. Malaysian Propolis (MP) has been reported to exhibit high 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and ferric reducing antioxidant power (FRAP) values. Herein, we report the antioxidant properties and cardioprotective properties of MP in isoproterenol- (ISO-) induced myocardial infarction in rats. Male Wistar rats (n = 32) were pretreated orally with an ethanol extract of MP (100 mg/kg/day) for 30 consecutive days. Subcutaneous injection of ISO (85 mg/kg in saline) for two consecutive days caused a significant increase in serum cardiac marker enzymes and cardiac troponin I levels and altered serum lipid profiles. In addition significantly increased lipid peroxides and decreased activities of cellular antioxidant defense enzymes were observed in the myocardium. However, pretreatment of ischemic rats with MP ameliorated the biochemical parameters, indicating the protective effect of MP against ISO-induced ischemia in rats. Histopathological findings obtained for the myocardium further confirmed the biochemical findings. It is concluded that MP exhibits cardioprotective activity against ISO-induced oxidative stress through its direct cytotoxic radical-scavenging activities. It is also plausible that MP contributed to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation.

Cardioprotective Effect of Aloe vera Biomacromolecules Conjugated with Selenium Trace Element on Myocardial Ischemia-Reperfusion Injury in Rats.

The present study was undertaken to evaluate the cardioprotection potential and underlying molecular mechanism afforded by a selenium (Se) polysaccharide (Se-AVP) from Aloe vera in the ischemia-reperfusion (I/R) model of rats in vivo. Myocardial I/R injury was induced by occluding the left anterior descending coronary artery (LAD) for 30min followed by 2-h continuous reperfusion. Pretreatment with Se-AVP (100, 200, and 400mg/kg) attenuated myocardial damage, as evidenced by reduction of the infarct sizes, increase in serum and myocardial endogenous antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GSH), and catalase (CAT)), and decrease in the malondialdehyde (MDA) level in the rats suffering I/R injury. This cardioprotective activity afforded by Se-AVP is further supported by the decreased levels of cardiac marker enzymes creatine kinase (CK) and lactate dehydrogenase (LDH), as well as the rise of myocardial Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities in I/R rats. Additionally, cardiomyocytic apoptosis was measured by terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining and the result showed that the percent of TUNEL-positive cells in myocardium of Se-AVP-treated groups was lower than I/R rats. In conclusion, we clearly demonstrated that Se-AVP had a protective effect against myocardial I/R injury in rats by augmenting endogenous antioxidants and protecting rat hearts from oxidative stress-induced myocardial apoptosis.

Cardioprotective potential of Dendrobiumofficinale Kimura et Migo against myocardial ischemia in mice.

Dendrobiumofficinale Kimura et Migo has been used for thousands of years to promote body fluid production; however, little is currently known regarding its effects on the heart. The present study aimed to explore the cardioprotective potential of the water extract of Dendrobiumofficinale Kimura et Migo (DOE) on myocardial ischemia in mice. A mouse model of myocardial ischemia was induced following ligation of the left anterior descending coronary artery. Prior to the operation, mice were administered a vehicle or DOE for 2weeks. Following the operation, ST elevation was measured. To estimate the extent of myocardial damage, infarct size analysis and histopathological examination were performed. The activities of cardiac marker enzymes [creatine kinase (CK)‑MB and lactate dehydrogenase (LDH)] and antioxidative indicators [malondialdehyde (MDA) and superoxide dismutase (SOD)] were also analyzed to explore the underlying mechanisms. Treatment with DOE decreased infarct size and the number of apoptotic cardiomyocytes; reduced serum CK‑MB, LDH and MDA activities; and increased SOD levels. According to western blotting, DOE conferred protection against myocardial ischemic injury via the regulation of Meis1 expression. These results indicated that DOE may exert potential cardioprotective effects against myocardial ischemia; these effects may be associated with its antioxidant activity, and its ability to inhibit cardiac cell apoptosis and to regulate Meis1 expression.

Kampeferol protects against oxidative stress and apoptotic damage in experimental model of isoproterenol-induced cardiac toxicity in rats

BackgroundMyocardial infarction (MI) continues to be associated with high morbidity and mortality worldwide despite the availability of current therapeutic modalities. Kaempferol (KMP), a dietary flavonoid, possesses good antioxidant, immunomodulatory and anti-apoptotic properties and has been evaluated in the present study for its role in mitigating myocardial injury following MI. PurposeIn this study, the ability of KMP to protect heart against isoproterenol (ISO) induced oxidative stress and myocardial infarction was evaluated. Material and methodsMale Wistar rats (n=48) were administered KMP (5, 10 & 20mg/kg/day, i.p.) or vehicle for 15 days with ISO, 85mg/kg, subcutaneously, for 2 consecutive days was also administered at 24h interval on the 13th and 14th days. On the 15th day, rats were anaesthetized and right coronary artery was cannulated to record hemodynamic parameters. Later on blood sample was collected and heart was removed to estimate biochemical, histopathological, ultrastructural and immuohistochemical studies respectively. ResultsISO-treated rats showed a significant reduction in arterial pressure, maximum rate of development of left ventricular pressure and increase in left ventricular end-diastolic pressure. Also, there was a significant decrease in antioxidant enzyme levels such as superoxide dismutase, catalase and glutathione and increase in the level of malondialdehyde and serum TNF-α and IL-6 levels. In addition, the cardiac injury markers such as creatine kinase-MB and lactate dehydrogenase were increased in the serum. Furthermore, immunohistochemistry revealed an increased Bax/Bcl-2 ratio in the myocardium. KMP (5, 10 and 20mg/kg) dose dependently restored hemodynamic, left ventricular functions, decreased cardiac injury marker enzymes in serum, increased antioxidant levels, reduced lipid peroxidation and TNF-α level and apoptosis. Histopathological and ultrastructural studies support the protective effect of KMP in ISO-induced myocardial infarcted rats. ConclusionThus, the present study revealed that KMP mitigates myocardial damage in ISO-induced cardiac injury by maintaining hemodynamic and biochemical parameters and reducing inflammation owing to its anti-apoptotic, anti-inflammatory and antioxidant activities. It may be concluded that a diet containing KMP may be beneficial in those who are at the risk of myocardial injury.

Flax lignan concentrate attenuate hypertension and abnormal left ventricular contractility via modulation of endogenous biomarkers in two-kidney-one-clip (2K1C) hypertensive rats

The present investigation was designed to study the effect of flax lignan concentrate obtained from Linum usitatissimum L., Linaceae, in two-kidney, one clip (2K1C) hypertension model in Wistar rats. 2K1C Goldblatt model rats were divided randomly into six groups: sham, 2K1C control, captopril (30mg/kg), flax lignan concentrate (200, 400 and 800mg/kg). Flax lignan concentrate and captopril were administered daily for eight consecutive weeks. Sham-operated, and 2K1C control rats received the vehicle. Treatment with flax lignan concentrate (400 and 800mg/kg) significantly and dose-dependently restored the hemodynamic parameters systolic blood pressure, diastolic blood pressure, mean arterial blood pressure and left ventricular functions. The flax lignan concentrate significantly restored the elevated hepatic, renal and cardiac marker enzymes in the serum. It also restored the organs weights (kidney and heart), serum electrolyte level and histological abnormalities. Furthermore, flax lignan concentrate significantly elevated the level of biochemical markers that is enzymatic antioxidants superoxide dismutase, glutathione and decreased malondialdehyde in the heart and kidney tissues. Meanwhile, we found that plasma nitric oxide and plasma nitric oxide synthase contents were significantly increased in the flax lignan concentrate-treated group, and plasma endothelin-1 and renal angiotensin-II levels were significantly lower than 2K1C hypertensive group. In conclusion, the antihypertensive and antioxidant effect of flax lignan concentrate were dose-dependent and at the highest dose (i.e. 800mg/kg) similar to those of captopril (30mg/kg). It is suggested that flax lignan concentrate reduced blood pressure by reduction of renal angiotensin-II level, inhibition of plasma endothelin-1 production, induction of the nitric oxide, nitric oxide synthase and in vivo antioxidant defense system.

Protective Effect of Adansonia digitata against Isoproterenol-Induced Myocardial Injury in Rats

ABSTRACTThe baobab fruit (Adansonia digitata) was analyzed for proximate composition, amino acids, and minerals. The fruit pulp was found to be a good source of carbohydrates, proteins, phenols, and substantial quantities of K, Ca, and Mg. Amino acid analyses revealed high glutamic and aspartic acid, but the sulfur amino acids were the most limited. The present study was designed to investigate the role of Adansonia digitata (Baobab fruit pulp) against isoproterenol induced myocardial oxidative stress in experimental rats by demonstrating the changes in tissue cardiac markers, some antioxidant enzymes, interlukin-1 β (IL-1 β), monocyte chemoattractant protein-1(MCP-1), myeloperoxidase (MPO), Collagen-1, galectin-3, and serum corticosterone. The activities of enzymatic antioxidant glutathione peroxidase (GPX) and non-enzymatic antioxidant reduced glutathione (GSH) in the heart tissue; additionally, histopathological examination of the heart was estimated. Male albino rats were randomly divided into four groups of ten animals each. Group I served as normal control animal. Group II animals received isoproterenol (ISP) (85 mg/kg body weight intraperitonealy (i.p.) to develop myocardial injury. Group III were myocardial oxidative animals treated with Baobab fruit pulp (200 µg/rats/day) for 4 weeks. Group IV received Baobab fruit pulp only. The data suggested an isoproterenol increase in levels of cardiac marker enzymes [creatine kinase MB (CK- MB), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST)], IL-1ß, MCP-1, MPO, Collagen, and galectin-3, with concomitant decrease in the activities GPX and GSH in heart tissue as well as corticosterone in serum. Baobab fruit pulp brings all the parameters to near normal level in ISP-induced myocardial infarction in rats. Histopathological examination of heart tissue of ISP-administered model rat showed infiltration of inflammatory cells and congestion in the blood vessels. However, treatment with Baobab fruit pulp (200 µg/rats/day) showed predominantly normal myocardial structure and no inflammatory cell infiltration. It has been concluded that Baobab fruit pulp has cardio protective effect against ISP-induced oxidative stress in rats.

Flax lignan concentrate reverses alterations in blood pressure, left ventricular functions, lipid profile and antioxidant status in DOCA-salt induced renal hypertension in rats

Context Earlier we reported cardioprotective, antihyperlipidemic, and in vitro antioxidant activity of flax lignan concentrate (FLC) obtained from the seeds of Linum usitatissimum L. (Linaceae).Objective To investigate the effect of FLC in deoxycorticosterone acetate (DOCA)-salt induced experimental renal hypertension in rats. Materials and methods Hypertension was induced in uninephrectomized (UNTZD) male Wistar rats (230–280 g) by injecting DOCA (25 mg/kg, subcutaneously, twice weekly) and supplementing 1% NaCl in drinking water for 5 weeks. The rats were divided in six groups. Captopril (30 mg/kg, p.o.) and FLC (200, 400 and 800 mg/kg, p.o.) were administered daily to the rats of groups III–VI, respectively, for 5 weeks. Various hemodynamic and biochemical parameters were investigated as well as histology of kidney and heart were carried out. Results In this study, the FLC (400 and 800 mg/kg) significantly (p < 0.01, p < 0.001) decreased the systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure. It also significantly (p < 0.01, p < 0.001) decreased elevated end diastolic pressure (EDP), dP/dt max and dP/dt min, organs weights (kidney and heart) and activities of hepatic, renal and cardiac marker enzymes in the serum. Furthermore, FLC (400 and 800 mg/kg) significantly (p < 0.01, p < 0.001) restored altered antioxidant status, serum electrolyte level, lipid profile values, and histological abnormalities. Captopril (30 mg/kg) showed maximum antihypertensive effect but low dose of FLC (200 mg/kg) was not enough to show the antihypertensive activity. Conclusion FLC possessed antihypertensive effect via modulation of endogenous enzymes in DOCA-salt induced renal hypertension in rats.

Adverse Effects of Combinatorial Therapy of Vildagliptin and Insulin on Cardiac Tissues in Diabetic Rats

Objectives: This study is aimed to evaluate the cardiovascular adverse effects of fixed dose combination of vildagliptin (10 mg/kg body weight) and insulin (0.27 I.U/kg body weight) on alloxan induced diabetic rats. Methods and Analysis: The cardiac tissues were weighed and homogenized using ice cold phosphate buffer, centrifuged and the supernatant used for further parameters. The different parameters were measured spectrophotometrically and statistical analysis of data was done by ANOVA followed by dunnet's post hoc test. The test samples consist of diabetic animal fed with vildagliptin and insulin as monotherapies and also as combinatorial therapy and the approach used for comparing them is by SPSS data analysis software version 19.0. Findings: The histopathological studies show that in combinatorial therapy of vildagliptin and insulin in alloxan an induced diabetic rat shows pathological lesions, inflammatory infiltration and eosinophylic cytoplasm. With regard to cardiac marker enzymes their levels were significantly elevated in combinatorial therapy showing cardiac damage. With regard to lipid profile the total cholesterol has been significantly reduced in combinatorial therapy showing it was not properly metabolized. These results were analysed by dunnet's post hoc test and the level of significance was set at p<0.05. The drugs are producing severe adverse effects only at the post clinical trial stage. Our studies focus on the adverse effects produced by the drugs at the post clinical trial stage. Monitoring adverse drug reaction is still at a nascent stage owing to lack of awareness and healthcare professionals abstaining from reporting negative effects of pharmaceuticals. So our studies will be really helpful for developing new drugs which are devoid of adverse effects. Applications and Improvement: Our research will be a great resource for the pharmaceutical sector to develop new drugs which are devoid of all these adverse effects.

Cardioprotective activity of Limonia acidissima against Isoproterenol Induced Myocardial Infarction in Rats

The objective of the current study is evaluate the cardioprotective activity of ethanolic fruit extract of Limonia acidissima against isoproterenol induced myocardial infarction in rats. The protective activity of Limonia acidissima was assessed by estimating the cardiac marker enzymes (Creatinine Phosphokinase and Lactate Dehydrogenase) and antioxidants enzymes (superoxide dismutase and Catalase). Thirty male Sprague-Dawley rats (180–220 gm) were randomly allocated in 5 groups of 6 each. Group I served as control, II to V animals were Isoproterenol (85mg/kg) induced myocardiaol infracted animals, pre treated with the reference control Lipistat (350mg/kg) and ethanolic fruit extract of Limonia acidissima (200 and 400 mg/kg). All the test drugs were administered orally for 15 days. On 16th day the blood was collected and subjected to the estimation of cardiac marker enzymes. The animals were sacrificed; hearts were homogenized and used for the estimation of antioxidant enzymes. The result shows that, Limonia acidissima significantly decreased the cardiac marker enzyme and increased the antioxidant enzymes. Limonia acidissima produced a dose dependent cardioprotective effect against the acute cardiac damage induced by Isoproterenol in rats. From the result it was concluded that, Limonia acidissima produced cardioprotective activity against isoproterenol induced cardiac damage in rats which was mediated by its antioxidant property.

Prognostic Potential of Serum Biomarkers as Predictors for Cardiovascular Complications and Disease Progression in Chronic Kidney Disease Patients

Aim: Chronic Kidney Disease (CKD) is characterized by progressive loss of kidney function over a period of time. The aim of the study is to determine the prognostic potential of serum biomarkers for cardiovascular complications and disease progression in chronic kidney disease patients. Materials and Methods: This retrospective observational study was carried out in the nephrology department of a multispecialty hospital for a period of two months. Clinical and biochemistry reports of 499 CKD patients were collected in designed case report forms. All statistical analysis was carried out using International Business Machine (IBM) Statistical Package for Social Sciences (SPSS) 17.0. Results: A direct correlation was observed between cardiac enzyme markers and phosphate levels. The product of Glycated Hemoglobin (HbA1c) and number of years of Diabetes Mellitus (DM) as predictive risk factors for development and progression of nephropathy (DN-CKD). Conclusion: This study has attempted to evaluate altered serum biomarkers as potential prognostic factors of cardiovascular complication and progressive renal impairment in CKD patients. Further prospective studies are required to gain deep insights into this and thereby aid in making significant clinical decisions.

Pseudoaneurysm of the Right Coronary Artery Masquerading as a Right Atrial Mass

A 63-year-old man under concomitant antibiotic therapy for persistent bronchitis was referred from his general practitioner for progressive dyspnea and associated chest pain. Inflammatory parameters were elevated. Serial cardiac marker enzyme levels, including Troponin I, were within normal values. Thoracic CT-angiogram and echocardiogram showed a 3 cm hyperdense mass in the right atrioventricular groove with focal subepicardial expansion along the lateral atrial wall

Sundarban Honey Confers Protection against Isoproterenol-Induced Myocardial Infarction in Wistar Rats.

The present study was designed to investigate the cardioprotective effects of Sundarban honey (SH) in rats with isoproterenol- (ISO-) induced myocardial infarction. Adult male Wistar Albino rats were pretreated with Sundarban honey (5 g/kg) daily for a period of 6 weeks. After the treatment period, ISO (85 mg/kg) was subcutaneously injected into the rats at 24 h intervals for 2 days. ISO-induced myocardial damage was indicated by increased serum cardiac specific troponin I levels and cardiac marker enzyme activities including creatine kinase-MB, lactate dehydrogenase, aspartate transaminase, and alanine transaminase. Significant increases in serum total cholesterol, triglycerides, and low-density lipoprotein-cholesterol levels were also observed, along with a reduction in the serum high-density lipoprotein-cholesterol level. In addition to these diagnostic markers, the levels of lipid peroxide products were significantly increased. The activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase were significantly decreased in the hearts after ISO-induced myocardial infarction. However, pretreatment of ischemic rats with Sundarban honey brought the biochemical parameters to near normalcy, indicating the protective effect of Sundarban honey against ISO-induced ischemia in rats. Histopathological findings of the heart tissues further confirmed the biochemical findings, indicating that Sundarban honey confers protection against ISO-induced oxidative stress in the myocardium.

Thymol, a dietary monoterpene phenol abrogates mitochondrial dysfunction in β-adrenergic agonist induced myocardial infarcted rats by inhibiting oxidative stress

Mitochondrial dysfunction has been suggested to be one of the important pathological events in isoproterenol (ISO), a synthetic catecholamine and β-adrenergic agonist induced myocardial infarction (MI). In this context, we have evaluated the impact of thymol against ISO induced oxidative stress and calcium uniporter malfunction involved in the pathology of mitochondrial dysfunction in rats. Male albino Wistar rats were pre and co-treated with thymol (7.5 mg/kg body weight) daily for 7 days. Isoproterenol (100 mg/kg body weight) was subcutaneously injected into rats on 6th and 7th day to induce MI. To explore the extent of cardiac mitochondrial damage, the activities/levels of cardiac marker enzymes, mitochondrial lipid peroxidation products, antioxidants, lipids, calcium, adenosine triphosphate and multi marker enzymes were evaluated. Isoproterenol induced myocardial infarcted rats showed a significant increase in the activities of cardiac diagnostic markers, heart mitochondrial lipid peroxidation, lipids, calcium, and a significant decrease in the activities/levels of heart mitochondrial superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, isocitrate, malate, α-ketoglutarate and NADH-dehydrogenases, cytochrome-C-oxidase, and adenosine triphosphate. Thymol pre and co-treatment showed near normalized effects on all the biochemical parameters studied. Transmission electron microscopic findings and mitochondrial swelling studies confirmed our biochemical findings. The in vitro study also revealed the potent free-radical scavenging activity of thymol. Thus, thymol attenuates the involvement of ISO against oxidative stress and calcium uniporter malfunction associated with mitochondrial dysfunction in rats.

Comparative evaluation of HMG CoA reductase inhibitors in experimentally-induced myocardial necrosis: Biochemical, morphological and histological studies

The present study was carried out to evaluate the protective effect of different statins on isoproterenol (ISO) induced myocardial necrosis. Atorvastatin, rosuvastatin, fluvastatin, simvastatin and pravastatin (10mg/kg/day) were administered for 12 weeks. After pretreatment of 12 weeks myocardial necrosis was induced by subsequent injection of ISO (85mg/kg/day, s.c.) to wistar rats. Serum biochemical parameters like glucose, lipid profile, cardiac markers and transaminases were evaluated. Animals were killed and heart was excised for histopathology and antioxidant study. Statins pretreated rats showed significant protection against ISO induced elevation in serum biochemical parameters and serum level of cardiac marker enzymes and transaminase level as compared to ISO control group. Mild to moderate protection was observed in different statins treated heart in histopathology and TTC stained sections. Result from our study also revealed that statins could efficiently protect against ISO intoxicated myocardial necrosis by impairing membrane bound enzyme integrity and endogenous antioxidant enzyme levels. Amongst all statins used, rosuvastatin and pravastatin were found to have maximum cardio-protective activity against ISO induced myocardial necrosis as compared to other statins.

Effect of Tinospora cordifolia (Guduchi) root extract on Cardiotoxicity in streptozotocin induced diabetic rats.

The aim of this study is to explore the effect of Tinospora cordifolia (Guduchi) on cardiotoxicity in streptozotocin induced diabetic rats. All animals were divided into 8 groups of 5 animals each, fed with High fat diet (HFD) except the ones in Sham, NPD and NPD-C-I groups. Food and water intake were monitored daily at the same time during the experimental period. The Food Efficiency Ratio (FER) was calculated during the experiment period. All the animals were pretreated as per the treatment protocol. Streptozotocin; STZ (50mg/ Kg) was administered subcutaneously to induce the diabetes which was confirmed in all the administered groups by testing blood glucose level after 48 hours. Cardiotoxicity was induced by administering isoprenaline (85mg/Kg). Troponin was checked after 4-5 hours of second isoprenaline injection to confirm cardiac damage. At the end of the study the animals were weighed and then sacrificed with high dose of Diethyl ether. Blood samples were collected from retro-orbital plexus and were used for biochemical estimations. The hearts were excised immediately and were weighed. Photomicrographs were taken for gross examination rest of the hearts were kept in 10% Formalin solution for histopathological studies. Pretreatment with Tinospora cordifolia (200 mg/kg ) showed very significant improvement against Streptozotocin induced diabetes (p< 0.01) as blood glucose level were found to be decreased when compared to the untreated D-HFD group. The Food efficiency ratio (FER) was found to be significantly increased when compared to D-HFD (p<0.01). Significant decrease in the elevated activities of the cardiac marker enzymes, viz, alanine transaminase (ALT) (p < 0.01), lactate dehydrogenase (LDH) (p < 0.01), creatinine kinase (CK-MB) (p < 0.01) and negative troponin test were observed. The observed results were further confirmed by histopathological findings which indicated that Tinospora cordifolia (200mg/Kg) shows highly significant reduction in cardiotoxicity and considerable improvement, compactly arranged muscle fibres with minimum interstitial tissue, long spindle shaped vascular nuclei and well marked muscles striations.The findings of this study indicate that Tinospora cordifola (Guduchi) root extract exerts potent cardioprotection against isoprenaline induced cardiotoxicity in diabetic rats. This effect is comparable with that of carvedilol and pioglitazone.

Cardioprotective Effects of Tannic Acid on Isoproterenol-Induced Myocardial Injury in Rats: Further Insight into 'French Paradox'.

Tannic acid (TA) is a polyphenolic compound, which has shown diverse pharmacological effects with antimutagenic, anticarcinogenic and antibactericidal properties. However, cardioprotective effects of TA have not been reported. To investigate the protective effects of TA, rats were administered TA for 7 days and then intoxicated with isoproterenol (ISO). Myocardial ischemia injury was indicated by changes in electrocardiographic (ECG) patterns, morphology and cardiac marker enzymes. Furthermore, protein expression levels of c-fos, c-jun, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cleaved-caspase-3 and -9 were analyzed by immunohistochemistry, and activities of apoptosis-related proteins Bax, Bcl-2, caspase-3 and nuclear factor kappa B (NF-κB) were detected by Western blot. Pretreatment with TA ameliorated changes in morphology and ECG, reduced activities of marker enzymes, suppressed overexpression of apoptosis-related proteins, upregulated expression of antioxidants. Moreover, TA pretreatment contributed to the decrease in ratio of Bax/Bcl-2, as well as reduced expression of TNF-α, IL-1β, caspase-3, cleaved-caspase-3 and -9. TA displayed cardioprotective effects, which may be attributed to lowering of Bax/Bcl-2 ratio, c-fos and c-jun expression and inhibition of NF-κB activation, as well as oxidative stress, inflammation and apoptosis. These findings provide further insight into the 'French paradox' and the mechanisms underlying the beneficial effects of TA. Copyright © 2015 John Wiley & Sons, Ltd.

Tangeretin, a polymethoxylated flavone, modulates lipid homeostasis and decreases oxidative stress by inhibiting NF-κB activation and proinflammatory cytokines in cardiac tissue of streptozotocin-induced diabetic rats

The cardioprotective nature of tangeretin, a polymethoxylated flavone present in citrus fruits, was investigated by assessing the key markers of heart, lipid profiles, oxidative stress, proinflammatory cytokines and ultrastructural alterations in streptozotocin-induced diabetic rats. Oral administration of tangeretin (100 mg/kg body weight/day) for 30 days to diabetic rats reversed the body weight and heart weight changes by its insulinotropic action which in turn decreased the plasma and cardiac lipid profiles through modification activities of key enzymes of lipid metabolism in liver and increased the GLUT4 expression in the heart of diabetic rat. Moreover, tangeretin treatment increased the activities of antioxidant enzymes by decreasing the levels of lipid peroxidation and extent of inflammatory cytokines and cardiac marker enzymes in both plasma and heart of diabetic rats. Further, tangeretin blunted the rise in cardiac [Ca2+] and [Na+] whereas it increased the activities of Ca2+-ATPase and Na+/K+-ATPase in diabetic rats. The results of biochemical tests together with histological observations suggest that tangeretin treatment plays a beneficial role in regulating diabetes and its associated complications in the heart. The effect produced by tangeretin on various parameters was comparable to that of glibenclamide – an antidiabetic drug.

Cardioprotective Potential of Polyphenolic Rich Green Combination in Catecholamine Induced Myocardial Necrosis in Rabbits.

The present study was designed to develop safer, effective, and viable cardioprotective herbal combination to control oxidative stress related cardiac ailments as new alternatives to synthetic drugs. The synergetic cardioprotective potential of herbal combination of four plants T. arjuna (T.A.), P. nigrum (P.N), C. grandiflorus (C), and C. oxyacantha (Cr) was assessed through curative and preventive mode of treatment. In preventive mode of treatment, the cardiac injury was induced with synthetic catecholamine (salbutamol) to pretreated rabbits with the proposed herbal combination for three weeks. In curative mode of treatment, cardiotoxicity/oxidative stress was induced in rabbits with salbutamol prior to treating them with plant mixture. Cardiac marker enzymes, lipids profile, and antioxidant enzymes as biomarker of cardiotoxicity were determined in experimental animals. Rabbits administrated with mere salbutamol showed a significant increase in cardiac marker enzymes and lipid profile and decrease in antioxidant enzymes as compared to normal control indicating cardiotoxicity and myocardial cell necrosis. However, pre- and postadministration of plant mixture appreciably restored the levels of all biomarkers. Histopathological examination confirmed that the said combination was safer cardioprotective product.

The Protective Effects of Salidroside from Exhaustive Exercise-Induced Heart Injury by Enhancing the PGC-1 α -NRF1/NRF2 Pathway and Mitochondrial Respiratory Function in Rats.

Objective. To test the hypothesis that salidroside (SAL) can protect heart from exhaustive exercise-induced injury by enhancing mitochondrial respiratory function and mitochondrial biogenesis key signaling pathway PGC-1α–NRF1/NRF2 in rats. Methods. Male Sprague-Dawley rats were divided into 4 groups: sedentary (C), exhaustive exercise (EE), low-dose SAL (LS), and high-dose SAL (HS). After one-time exhaustive swimming exercise, we measured the changes in cardiomyocyte ultrastructure and cardiac marker enzymes and mitochondrial electron transport system (ETS) complexes activities in situ. We also measured mitochondrial biogenesis master regulator PGC-1α and its downstream transcription factors, NRF1 and NRF2, expression at gene and protein levels. Results. Compared to C group, the EE group showed marked myocardium ultrastructure injury and decrease of mitochondrial respiratory function (P < 0.05) and protein levels of PGC-1α, NRF1, and NRF2 (P < 0.05) but a significant increase of PGC-1α, NRF1, and NRF2 genes levels (P < 0.05); compared to EE group, SAL ameliorated myocardium injury, increased mitochondrial respiratory function (P < 0.05), and elevated both gene and protein levels of PGC-1α, NRF-1, and NRF-2. Conclusion. Salidroside can protect the heart from exhaustive exercise-induced injury. It might act by improving myocardial mitochondrial respiratory function by stimulating the expression of PGC-1α–NRF1/NRF2 pathway.

Cardioprotective Effects of Tualang Honey: Amelioration of Cholesterol and Cardiac Enzymes Levels

The present study was designed to investigate the cardioprotective effects of Malaysian Tualang honey against isoproterenol- (ISO-) induced myocardial infarction (MI) in rats by investigating changes in the levels of cardiac marker enzymes, cardiac troponin I (cTnI), triglycerides (TG), total cholesterol (TC), lipid peroxidation (LPO) products, and antioxidant defense system combined with histopathological examination. Male albino Wistar rats (n = 40) were pretreated orally with Tualang honey (3 g/kg/day) for 45 days. Subcutaneous injection of ISO (85 mg/kg in saline) for two consecutive days caused a significant increase in serum cardiac marker enzymes (creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and aspartate transaminase (AST)), cTnI, serum TC, and TG levels. In addition, ISO-induced myocardial injury was confirmed by a significant increase in heart lipid peroxidation (LPO) products (TBARS) and a significant decrease in antioxidant enzymes (SOD, GPx, GRx, and GST). Pretreatment of ischemic rats with Tualang honey conferred significant protective effects on all of the investigated biochemical parameters. The biochemical findings were further confirmed by histopathological examination in both Tualang-honey-pretreated and ISO-treated hearts. The present study demonstrates that Tualang honey confers cardioprotective effects on ISO-induced oxidative stress by contributing to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation.