(−)Epigallocatechin-gallate (EGCG) prevents mitochondrial damage in isoproterenol-induced cardiac toxicity in albino Wistar rats: A transmission electron microscopic and in vitro study

Altered mitochondrial function and free radical-mediated tissue damage have been suggested as important pathological events in isoproterenol (ISO)-induced cardiotoxicity. This study was undertaken to know the preventive effect of (-)epigallocatechin-gallate (EGCG) on mitochondrial damage in ISO-induced cardiotoxicity in male Wistar rats. Rats were pretreated with EGCG (30 mg/kg) orally using an intragastric tube daily for a period of 21 days. After that, ISO (100mg/kg) was subcutaneously injected to rats at intervals of 24h for 2 days. ISO-induced rats showed significant increase in mitochondrial lipid peroxidation products (thiobarbituric acid reactive substances and lipid hydroperoxides) and significant decrease in mitochondrial antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and reduced glutathione). Also, significantly decreased activities of tricarboxylic acid cycle enzymes such as isocitrate, succinate, malate and alpha-ketoglutarate dehydrogenases and respiratory chain marker enzymes such as NADH-dehydrogenase and cytochrome-c-oxidase were observed in mitochondrial heart of myocardial infarcted rats. Prior treatment with EGCG (30mg/kg body weight) significantly prevented these alterations and restored normal mitochondrial function. Transmission electron microscopic findings also correlated with these biochemical parameters. In vitro studies on the effect of EGCG on scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS(+)), superoxide anion (O(-)), and hydroxyl (OH) radicals also confirmed the free radical scavenging and antioxidant activity of EGCG. Thus, the observed effects are due to the free radical scavenging and antioxidant potential of EGCG. Thus, this study confirmed the preventive effect of EGCG on isoproterenol-induced mitochondrial damage in experimentally induced myocardial infarction in Wistar rats.     

Preventive effect of S-allylcysteine on lipid peroxides and antioxidants in normal and isoproterenol-induced cardiotoxicity in rats: a histopathological study

The consumption of diets rich in plant foods are associated with a reduced risk of cardiovascular diseases. This study was aimed to evaluate the role of S-allylcysteine (SAC) in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (150 mg/kg) to Wistar rats showed a significant decrease in the activities of marker enzymes such as creatine kinase, lactate dehydrogenase, aspartate and alanine transaminases in heart and a significant increase in the levels of thiobarbituric acid reactive substances and lipid hydroperoxides in plasma and heart. ISO-induced rats also showed a significant decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase in heart and the levels of glutathione and ascorbic acid in plasma and heart. Oral administration of SAC (100 and 150 mg/kg) to ISO-treated rats daily for a period of 45 days caused a significant increase in the activities of marker enzymes and improved the antioxidant status by decreasing lipid peroxidative products and increasing the activities of antioxidant enzymes and the levels of nonenzyomic antioxidants. Administration of SAC to normal rats did not show any significant effect. Histopathological findings of the myocardial tissue showed a protective role of SAC in ISO-treated rats. The effect at a dose of 150 mg/kg of SAC was more pronounced than that of the dose 100mg/kg and brought back all the parameters to near normal. The effect exerted by 100 mg/kg of SAC was similar to that of alpha-tocopherol (60 mg/kg). The results of our study show that SAC possesses antioxidant activity in ISO-induced experimental MI.     

Preventive effect of naringin on lipid peroxides and antioxidants in isoproterenol-induced cardiotoxicity in Wistar rats: biochemical and histopathological evidences

This study was designed to evaluate the cardioprotective potential of naringin on lipid peroxides, enzymatic and nonenzymatic antioxidants and histopathological findings in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (85 mg/kg) to male Wistar rats showed a significant increase in the levels of thiobarbituric acid reactive substances and lipid hydroperoxides in plasma and the heart and a significant decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in the heart and the levels of reduced glutathione, vitamin C and vitamin E in plasma and heart and ceruloplasmin in plasma. Oral administration of naringin (10, 20 and 40 mg/kg, respectively) to ISO-induced rats daily for a period of 56 days showed a significant decrease in the levels of lipid peroxidative products and improved the antioxidant status by increasing the activities of antioxidant enzymes and nonenzymatic antioxidants. Histopathological findings of the myocardial tissue showed the protective role of naringin in ISO-induced rats. The effect at a dose of 40 mg/kg of naringin was more pronounced than that of the other two doses, 10 and 20mg/kg. The results of our study show that naringin possess anti-lipoperoxidative and antioxidant activity in experimentally induced cardiac toxicity.     

A biochemical, electrocardiographic, electrophoretic, histopathological and in vitro study on the protective effects of (-)epicatechin in isoproterenol-induced myocardial infarcted rats

(-) Epicatechin rich foods and (-) epicatechin improve cardiovascular function. Consumption of diets rich in flavonoids is associated with reduced risk of cardiovascular diseases. Oxidative stress resulting from increased production of free radicals associated with decreased levels of antioxidants in the myocardium plays a major role in the pathogenesis of myocardial infarction. This study aims to evaluate the preventive effects of (-) epicatechin on oxidative stress in isoproterenol-induced myocardial infarcted rats. Male Wistar rats were pretreated with (-) epicatechin (20mg/kg body weight) daily for 21 days. After pretreatment, isoproterenol (100mg/kg body weight) was injected into the rats at an interval of 24h for two days to induce myocardial infarction. Isoproterenol induced rat's electrocardiogram showed elevated ST segments and significant increase in the activity of serum creatine kinase-MB, level of serum troponin-T and increased intensities of serum lactate dehydrogenase 1 and 2-isoenzymes. The rats also showed significant increased levels of heart lipid peroxidation products and significant decreased activities of heart superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and levels of reduced glutathione. Pretreatment with (-) epicatechin revealed significant protective effects on all the biochemical parameters and electrocardiogram investigated. Histopathology of myocardium confirmed the present findings. The in vitro study on the effects of (-) epicatechin on scavenging free radical 1,1-diphenyl-2-picrylhydrazyl revealed the free radical scavenging potential of (-) epicatechin. Thus, (-) epicatechin exerts protective effects against isoproterenol-induced oxidative stress thereby reducing cardiac tissue damage by its free radical scavenging and antioxidant effects.     

Cardioprotective effect of fluvastatin on isoproterenol-induced myocardial infarction in rat

The present study was designed to investigate whether fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, would attenuate the acute myocardial infarction in isoproterenol-treated rat model via maintaining activities of endogenous antioxidant enzymes. Hemodynamic and electrocardiograph parameters were monitored and recorded continuously, cardiac marker enzymes and antioxidative parameters of plasma and heart tissues were measured, and histopathological examination of heart tissues was performed. Isoproterenol-treated rats showed lower of left-ventricular systolic pressure (LVSP), maximum (LVdP/dtmax) and minimum rate of developed left ventricular pressure (LVdP/dtmin), and higher of left ventricular end-diastolic pressure (LVEDP), in addition, a significant rise in ST-segment and increase in content of lactate dehydrogenase, glutamic oxalacetic transaminase, creatine kinase and malondialdehyde, as well as fall in activities of glutathione peroxidase, superoxide dismutase and catalase were observed. Oral administration of fluvastatin (5, 10 and 20 mg/kg, respectively) significantly prevented almost all the parameters of isoproterenol-induced heart failure and myocardial injury that mentioned above. The protective role of fluvastatin on isoproterenol-induced myocardial damage was further confirmed by histopathological examination. There was no significant change in heart rate in all experimental groups. Compared with control group, any indexes in sham rats treated with fluvastatin (20 mg/kg) alone were unaltered (all P>0.05). Our results suggest that fluvastatin has a significant effect on the protection of heart against isoproterenol-induced myocardial infarction through maintaining endogenous antioxidant enzyme activities.     

Coconut kernel protein in diet protects the heart by beneficially modulating endothelial nitric oxide synthase,tumor necrosis factor-alpha,and nuclear factor-kappaB expressions in experimental myocardial infarction

Previous studies conducted in our laboratory revealed that coconut kernel protein has a significant cardioprotective effect on isoproterenol-induced myocardial infarction in rats. In the present study, we explored the possible protective mechanism of coconut kernel protein during acute myocardial infarction. Coconut kernel protein (50 mg/100 g) was administered to Sprague-Dawley rats orally for 45 days. Isoproterenol (20 mg/100 g) was injected subcutaneously at an interval of 24 hours twice to induce myocardial infarction. Myocardial infarction was confirmed by the abnormal activities of cardiac marker enzymes in serum. Activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase were decreased (p < 0.05) in the heart of isoproterenol-treated rats, whereas pretreatment with coconut kernel protein increased (p < 0.05) these activities. An improved antioxidant status in these rats was further confirmed by the increased level of reduced glutathione and decreased level of lipid peroxidation products. Nitric oxide synthase (NOS) activity in the heart and nitrite level in blood were increased (p < 0.05) in coconut kernel protein-treated rats administered with isoproterenol compared to isoproterenol control rats. Coconut protein pretreatment upregulated the expression of endothelial nitric oxide synthase (eNOS), whereas expressions of nuclear factor-kappaB (NF-κB) and tumor necrosis factor-alpha (TNF-α) were downregulated in isoproterenol-treated rats. These findings suggest that the protective effects of coconut kernel protein may be mediated in part through upregulation of nitric oxide production, antioxidant mechanisms, and its ability to inhibit TNF-α and NF-κB activation.     

Protective role of curcumin in myocardial oxidative damage induced by isoproterenol in rats

This study was designed to investigate the effect of oral curcumin pretreatment (200 mg/kg) on isoproterenol-induced myocardial injury in rats. Isoproterenol (85 mg/kg, s.c., in two divided doses at 24 h intervals) administration induced a statistically significant increase (P < 0.01) in serum lactate dehydrogenase, creatine kinase, aspartate transaminase, and alanine transaminase activities and significant increase (P < 0.01) in myocardial lipid peroxides levels as compared to vehicle control rats. Furthermore, significant depletion (P < 0.01) of myocardial endogenous antioxidants viz. superoxide dismutase, catalase, and tissue glutathione levels were also found in the pathogenic control group, that is, isoproterenol only treated animals. Curcumin (200 mg/kg) pretreatment for 20 days in isoproterenol treated rats significantly lowered (P < 0.01) the serum lactate dehydrogenase, creatine kinase, aspartate transaminase, alanine transaminase, and myocardial lipid peroxides levels and increased the levels of myocardial endogenous antioxidants (superoxide dismutase, catalase, and tissue glutathione) as compared to pathogenic control rats. Furthermore, histological examination of rat's heart section confirmed myocardial injury with isoproterenol administration and near normal pattern with curcumin pretreatment. The results of our study provide clear evidence that the curcumin pretreatment enhances the antioxidant defense against isoproterenol-induced oxidative myocardial injury in rats and exhibit cardioprotective property.     

Effect of squalene on tissue defense system in isoproterenol-induced myocardial infarction in rats.

This study was designed to examine the effects of squalene on tissue antioxidant status in isoproterenol-induced myocardial infarction in male albino rats. Levels of diagnostic marker enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK)] in plasma, lipid peroxides, reduced glutathione, and the activities of glutathione-dependent antioxidant enzymes [glutathione peroxidase (GPx) and glutathione-S-transferase (GST)] and antiperoxidative enzymes [catalase (CAT) and superoxide dismutase (SOD)] in the heart tissue of experimental groups of rats were determined. The prior administration of squalene at 2% level along with feed for 45 days significantly prevented the isoproterenol-induced elevation in the levels of diagnostic marker enzymes in plasma of experimental rats. Squalene also exerted an antioxidant effect against isoproterenol-induced myocardial infarction by blocking the induction of lipid peroxidation. A tendency to prevent the isoproterenol-induced alterations in the level of reduced glutathione and in the activities of glutathione-dependent antioxidant enzymes and antiperoxidative enzymes was also observed. The cardioprotective effect of squalene might be ascribable to its antioxidant property and membrane stabilizing action.     

Synergistic effect of nicorandil and amlodipine on mitochondrial function during isoproterenol-induced myocardial infarction in rats

The synergistic effects of nicorandil (KATP-channel opener) and amlodipine (calcium-channel blocker) on heart mitochondrial enzymes and the mitochondrial antioxidant defence system was examined on isoproterenol-induced myocardial infarction in rats. The rats given isoproterenol (150 mg kg(-1) daily, i.p.) for two days showed significant changes in marker enzymes, mitochondrial enzymes and the mitochondrial defence system. Pre-co-treatment with nicorandil (2.5 mg kg(-1) daily, p.o.) and amlodipine (5.0 mg kg(-1) daily, p.o.) for 3 days significantly prevented these alterations and restored enzyme activity to near normal. These findings demonstrate the protective and synergistic effect of nicorandil and amlodipine in combination against isoproterenol-induced cardiac damage.     

Cardioprotective effect of tincture of Crataegus on isoproterenol-induced myocardial infarction in rats

Tincture of Crataegus (TCR), an alcoholic extract of the berries of hawthorn (Crataegus oxycantha), is used in herbal and homeopathic medicine. The present study was done to investigate the protective effect of TCR on experimentally induced myocardial infarction in rats. Pretreatment of TCR, at a dose of 0.5 mL/100 g bodyweight per day, orally for 30 days, prevented the increase in lipid peroxidation and activity of marker enzymes observed in isoproterenol-induced rats (85 mg kg(-1) s. c. for 2 days at an interval of 24 h). TCR prevented the isoproterenol-induced decrease in antioxidant enzymes in the heart and increased the rate of ADP-stimulated oxygen uptake and respiratory coupling ratio. TCR protected against pathological changes induced by isoproterenol in rat heart. The results show that pretreatment with TCR may be useful in preventing the damage induced by isoproterenol in rat heart.     

Effect of alpha-tocopherol on lipid peroxidation in isoproterenol induced myocardial infarction in rats

The effect of alpha-tocopherol pretreatment on lipid peroxidation and antioxidant status in isoproterenol induced myocardial infarction was studied in rats. Isoproterenol administered rats showed a significant increase in lipid peroxides in serum, heart and aorta. A significant increase in serum iron level with a significant decrease in iron binding capacity was also observed. The levels of antioxidants such as ceruloplasmin, glutathione and the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase decreased significantly in isoproterenol administered rats when compared to control. The activity of Na+K+ATPase decreased significantly and the activity of Ca2+ATPase increased significantly in heart and aorta of isoproterenol administered rats. alpha-tocopherol pretreated rats maintained the levels of antioxidants, membrane bound enzymes and activities of antioxidant enzymes near normal, on isoproterenol administration, thus establishing its effect as an antioxidant.     

Andrographis paniculata extract protect against isoproterenol-induced myocardial injury by mitigating cardiac dysfunction and oxidative injury in rats

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.     

Modulatory effect of fish oil on the myocardial antioxidant defense system in isoproterenol-induced myocardial infarction

The effect of fish oil treatment on the activities of antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-s-transferase, and glutathione, as well as the level of the lipid peroxidation marker thiobarbituric reactive substance was studied in isoproterenol-induced myocardial infarction (MI). To confirm the induction of MI by isoproterenol, we studied the activities of cardiac marker enzymes like creatinine kinase and lactate dehydrogenase and the level of troponin. The biochemical lesions due to the activation of lipid peroxidation and decrease in antioxidant status are significantly implicated in experimental isoproterenol-induced MI. The results indicate that the protective effect of fish oil is achieved by decreasing the peroxide concentration and normalizing antioxidant defense enzymes.     

Antioxidant activity of Pepticare, a herbomineral formulation, in experimentally induced renal and cardiac damage

Pepticare, a herbomineral formulation, was administered orally to rats at the dose levels of 125, 250, 500 and 1000 mg/kg to investigate its effect on isoproterenol-induced myocardial infarction and cisplatin-induced renal damage. The drug reduced the levels of serum creatine kinase (CK), glutamic oxaloacetate transaminase (GOT), lactate dehydrogenase (LDH) and uric acid in isoproterenol-induced cardiac damage. In cisplatin-induced renal damage, Pepticare reduced the serum levels of creatinine, urea, blood urea nitrogen (BUN) and uric acid. It was further found that administration of Pepticare increased the levels of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), membrane bound enzymes like Ca2+ ATPase, Mg2+ ATPase and Na+ K+ ATPase and decreased lipid peroxidation (MDA) in heart and kidney, respectively. Thus it can be concluded that Pepticare possesses antioxidant activity and protects the heart and kidney from damage caused by isoproterenol and cisplatin, respectively.     

Coconut Haustorium Maintains Cardiac Integrity and Alleviates Oxidative Stress in Rats Subjected to Isoproterenol-induced Myocardial Infarction

The present study evaluates the effect of aqueous extract of coconut haustorium on isoproterenol-induced myocardial infarction in Sprague Dawley rats. Rats were pretreated with aqueous extract of coconut haustorium (40 mg/100 g) orally for 45 days. After pretreatment, myocardial infarction was induced by injecting isoproterenol subcutaneously (20 mg/100 g body weight) twice at an interval of 24 h. Activity of marker enzymes like lactate dehydrogenase, creatinine kinase-MB, aspartate transaminase and alanine transaminase were increased in the serum and decreased in the heart of isoproterenol treated rats indicating cardiac damage. These changes were significantly reduced in haustorium pretreated rats. Moreover, an increase in the activities of antioxidant enzymes and decrease in the levels of peroxidation products were observed in the myocardium of coconut haustorium pretreated rats. Histopathology of the heart of these rats showed almost normal tissue morphology. From these results, it is clear that aqueous extract of coconut haustorium possess significant cardioprotective and antioxidant properties during isoproterenol-induced myocardial infarction in rats.     

Biochemical changes on the cardioprotective effect of nicorandil and amlodipine during experimental myocardial infarction in rats

The synergistic protective effect of nicorandil (KATP channel opener) and amlodipine (calcium channel blocker) on mitochondrial respiration and mitochondrial lipid contents were examined on isoproterenol-induced myocardial infarction in rats. The rats given isoproterenol (150 mg kg(-1) daily, i.p.) for 2 days showed significant changes in mitochondrial respiration and mitochondrial lipid profile levels. Pretreatment with nicorandil (2.5 mg kg(-1) daily, p.o.) and amlodipine (5.0 mg kg(-1) daily, p.o.) for 3 days significantly prevented these alterations and restored the mitochondrial respiration and mitochondrial lipid contents to near normal. Histopathological observations were also in correlation with the biochemical parameters. These findings indicate the synergistic protective effect of nicorandil and amlodipine on mitochondrial respiration and its membrane integrity during isoproterenol-induced cardiac damage.     

Methanol extract of Desmodium gangeticum roots preserves mitochondrial respiratory enzymes, protecting rat heart against oxidative stress induced by reperfusion injury

Ischaemia and reperfusion result in mitochondrial dysfunction, with decreased oxidative capacity, loss of cytochrome c and generation of reactive oxygen species. The aim of this study was to evaluate the effect of a methanol extract of Desmodium gangeticum (L) DC (Fabaceae) (DG) on lipid peroxidation and antioxidants in mitochondria and tissue homogenates of normal, ischaemic and ischaemia-reperfused rats. Myocardial lipid peroxidation products (thiobarbituric acid reactive substances; TBARS) in cardiac tissue homogenates and mitochondrial fractions were significantly increased during ischaemia reperfusion. Antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase (GPx) and glutathione reductase) in the myocardial tissue homogenate and mitochondria decreased significantly during ischaemia reperfusion, accompanied by a decreased activity of mitochondrial respiratory enzymes. Daily pretreatment of rats with DG (50 or 100 mgkg(-1)) orally for 30 days had a significant effect on the activity of mitochondrial and antioxidant enzymes. In-vitro studies showed that DG inhibited lipid peroxidation, and also scavenged hydroxyl and superoxide radicals. The concentrations required to scavenge 50% of the superoxide and hydroxyl radicals were 21 and 50.5 microgmL(-1), respectively. Administration of DG to normal rats did not have any significant effect on any of the parameters studied. The results of our study showed that DG possesses the ability to scavenge the free radicals generated during ischaemia and ischaemia reperfusion and thereby preserves the mitochondrial respiratory enzymes that eventually lead to cardioprotection.     

Effect of Piper betle on cardiac function,marker enzymes,and oxidative stress in isoproterenol-induced cardiotoxicity in rats

The present study was designed to investigate the cardioprotective potential of Piper betle (P. betle) against isoproterenol (ISP)-induced myocardial infarction in rats. Rats were randomly divided into eight groups viz. control, ISP, P. betle (75, 150, and 300?mg/kg) and P. betle (75, 150, and 300?mg/kg) + ISP treated group. P. betle leaf extract (75, 150, or 300?mg/kg) or saline was orally administered for 30 days. ISP (85?mg/kg, s.c.) was administered at an interval of 24?h on the 28^th and 29^th day and on day 30 the functional and biochemical parameters were measured. ISP administration showed a significant decrease in systolic, diastolic, mean arterial pressure (SAP, DAP, MAP), heart rate (HR), contractility (+LVdP/dt), and relaxation (?LVdP/dt) and increased left ventricular end-diastolic pressure (LVEDP). ISP also caused significant decrease in myocardial antioxidants; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and myocyte injury marker enzymes; creatine phosphokinase-MB (CK-MB) isoenzyme and lactate dehydrogenase (LDH) along with enhanced lipid peroxidation; thiobarbituric acid reacting species (TBARS) in heart. Pre-treatment with P. betle favorably modulated hemodynamic (SAP, DAP, and MAP) and ventricular function parameters (?LVdP/dt and LVEDP). P. betle pre-treatment also restored SOD, CAT, GSH, and GPx, reduced the leakage of CK-MB isoenzyme and LDH along with decreased lipid peroxidation in the heart. Taken together, the biochemical and functional parameters indicate that P. betle 150 and 300?mg/kg has a significant cardioprotective effect against ISP-induced myocardial infarction. Results of the present study suggest the cardioprotective potential of P. betle.     

Mitigation of mitochondrial dysfunction and regulation of eNOS expression during experimental myocardial necrosis by alpha-mangostin,a xanthonic derivative from Garcinia mangostana

Oxidative stress can play a key role in myocardial necrosis. The present study was designed to investigate the effect of alpha-mangostin (an antioxidant phytonutrient) on mitochondrial dysfunction and endothelial nitric oxide synthase (eNOS) expression during isoproterenol-induced myocardial necrosis in rats. Induction of rats with isoproterenol (ISO) (150?mg/kg body weight, intraperitoneally) for 2 days resulted in a significant decrease in the activities of respiratory chain enzymes (NADH dehydrogenase and cytochrome c oxidase), tricarboxylic acid cycle enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and alpha-ketoglutarate dehydrogenase), mitochondrial antioxidants (GPx, GST, SOD, CAT, and GSH), mitochondrial cytochromes (b, c, c1, and aa3), and adenosine triphosphate level. A marked elevation in mitochondrial lipid peroxidation was also observed in ISO-intoxicated rats. Pretreatment with alpha-mangostin (200?mg/kg body weight) orally for 8 days significantly attenuated these functional abnormalities and restored normal mitochondrial function, when compared to the ISO-intoxicated group of rats. Cardiac eNOS expression was assessed by Western blot. Cardiac eNOS expression and NO level were significantly suppressed in ISO-intoxicated rats. Pretreatment with alpha-mangostin extenuated ISO-induced diminution of eNOS expression and NO level. Transmission electron microscopic observations also correlated with these biochemical parameters. Hence, these findings conclude the ameliorative potential of alpha-mangostin against ISO-induced biochemical and morphological changes in mitochondria, which might be mediated through the NO pathway and by its ability at quenching free radicals.     

Ellagic acid ameliorates isoproterenol induced oxidative stress: Evidence from electrocardiological, biochemical and histological study

The present study was designed to evaluate the cardioprotective effects of ellagic acid against isoproterenol induced myocardial infarction in rats by studying electrocardiography, blood pressure, cardiac markers, lipid peroxidation, antioxidant defense system and histological changes. Male Wistar rats were treated orally with ellagic acid (7.5 and 15 mg/kg) daily for a period of 10 days. After 10 days of pretreatment, isoproterenol (100 mg/kg) was injected subcutaneously to rats at an interval of 24 h for 2 days to induce myocardial infarction. Isoproterenol administered rats showed significant changes in the electrocardiogram pattern, arterial pressure, and heart rate. Isoproterenol-induced rats also showed significant (P < 0.05) increase in the levels of serum troponin-I, creatine kinase, lactate dehydrogenase, C-reactive protein, plasma homocysteine, heart tissue thiobarbituric acid reactive substances and lipid hydro peroxides. The activities/levels of antioxidant system were decreased in isoproterenol-induced rats. The histopathological findings of the myocardial tissue evidenced myocardial damage in isoproterenol induced rats. The oral pretreatment of ellagic acid restored the pathological electrocardiographic patterns, regulated the arterial blood pressures and heart rate in the isoproterenol induced myocardial infarcted rats. The ellagic acid pretreatment significantly reduced the levels of biochemical markers, lipid peroxidation and significantly increased the activities/levels of the antioxidant system in the isoproterenol induced rats. An inhibited myocardial necrosis was evidenced by the histopathological findings in ellagic acid pretreated isoproterenol induced rats. Our study shows that oral pretreatment of ellagic acid prevents isoproterenol induced oxidative stress in myocardial infarction.