Protective Effect of Ipomoea biloba on Myocardial Antioxidant Status in Isoproterenol Induced Myocardial Infarction Male Albino Rats

The protective effect of ethanolic leaf extract of Ipomoea biloba in isoproterenol (ISO)-induced cardiotoxicity and the antioxidant activity involved in this protection were investigated in rats. Myocardial infraction was produced in rats with 20 mg/kg b.wt of ISO administered subcutaneously twice at an interval of 24 h. Effect of EEIB oral treatment for 28 days at two doses (100 mg and 200 mg/kg body weight) was evaluated against ISO – induced cardiac necrosis. Level of enzymatic (SOD, CAT, GPx and GST), non-enzymatic (GSH, Vitamin C and E) and of membrane bound ATPases (Na+K+ATPase, Mg2+ATPase and Ca2+ATPase) were assayed in heart homogenate. Significant myocardial infarction, depletion of endogenous antioxidants enzymatic and non-enzymatic were observed in ISO-treated animals when compared with the normal animals. Rats induced with ISO, showed a significant (P<0.05), decrease in the activities of GSH, Vitamin C and Eon comparison with normal rats. EEIB elicited a significant cardioprotective activity by elevated the levels of GSH, SOD, CAT, GPx and GR. A significant decrease in the activity of Na+/K+ ATPase and a corresponding increase in the activities of Ca2+ ATPase and Mg2+ ATPase were observed in isoproterenol induced rats when compared to normal control rats. Pretreatment with EEIB was able to efficiently prevent the increase in activity of Mg2+ ATPase and maintain the activities of Na+ /K+ ATPase and Ca2+ ATPase at near normality. There is no significant difference between the control and plant alone treated rats. The aim of this investigation is to evaluate the antioxidant effects on the main cardioprotective activity of ethanolic leaf extract Ipomoea biloba.

Sesamol Supplementation Mitigates Isoproterenol-Induced Cardiac Toxicity in Rats by Stabilizing Cardiac Mitochondrial and Lysosomal Enzymes

The current investigation was intended to evaluate the antimyocardial ischemic effects of sesamol on lactate dehydrogenase (LDH) isoenzymes, DNA damage, and mitochondrial and lysosomal enzyme activities in isoproterenol (ISO)-induced myocardial infarction (MI) in male albino Wistar strain rats. Rats that received ISO (85 mg/kg body weight (B.W) subcutaneously) for the first 2 consecutive days showed significant reduction in the activities of tricarboxylic acid (TCA) cycle enzymes (isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, malate dehydrogenase, and succinate dehydrogenase) and respiratory chain enzymes (cytochrome c oxidase and nicotinamide adenine dinucleotide hydrogen (NADH) dehydrogenase) in the heart mitochondria. The activities of the lysosomal enzymes (α-and β-glucosidases, α and β-galactosidases, β-glucuronidase and β-N-acetyl glucosaminidase and cathepsin-B and cathepsin-D) were increased significantly in the heart homogenate of ISO-induced MI rats. ISO injection also increased the % of tail DNA, tail length, and tail moment and decreased the % of head DNA. Pretreatment with sesamol (50 mg/kg B.W) every day for a period of 9 days prevented the above abnormalities induced by ISO. In conclusion, it can be inferred that administration of sesamol has a potent beneficial role against ISO-induced damage to the mitochondria, lysosomes, and DNA, thereby preventing MI.

Modulatory effect of some citrus (Citrus limon, Citrus reticulata, Citrus maxima) peels on monoamine oxidase, phosphodiesterase-5 and angiotensin-1 converting enzyme activities in rat heart homogenate

Background Citrus peels have been reported useful in folk medicine for the management of cardiovascular diseases, but there is dearth of information on the possible mechanisms for their therapeutic action. The aim of this study was to investigate the effect of methanolic extracts from some citrus [lime (Citrus limon), tangerine (Citrus reticulata), shaddock (Citrus maxima)] peels on some enzymes relevant to the management of cardiovascular diseases [monoamine oxidase (MAO), phosphodiesterase-5 (PDE-5) and angiotensin-1-converting enzyme (ACE)]. Methods Effect of methanolic extracts of lime, tangerine and shaddock peels on MAO, PDE-5 and ACE were carried out using standard methods. In addition, the ability of the extracts to prevent oxidative damage in rat heart homogenates was also investigated. Finally, the total polyphenol content of extracts was determined. Results The results revealed that methanolic extracts of lime, tangerine and shaddock peels inhibited MAO, PDE-5, ACE and pro-oxidants induced lipid peroxidation in rat heart homogenate in a concentration-dependent manner. Conclusions Findings in this study revealed citrus peel methanolic extracts as natural inhibitor of enzymes (MAO, PDE-5 and ACE) implicated in cardiovascular diseases. Therefore, citrus peels could help in the management of cardiovascular diseases possibly through inhibition of these enzymes.

CARDIOPROTECTIVE EFFECT OF INDIGOFERA TINCTORIA LINN. AGAINST MYOCARDIAL INFARCTION-INDUCED RATS

Objective: The aim and objective of the present study are to study the protective effects of ethanolic extract of Indica tinctoria (EEIT) in isoproterenol-induced acute myocardial infarction (AMI) in rats.Methods: The effect of two doses of isoproterenol (5 mg/kg and 8.5 mg/kg body weight) changes in aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), and total protein (TP) and lipid hydroperoxides, superoxide dismutase (SOD), and glutathione (GSH) in blood serum and heart homogenate, for the two consecutive days (29 and 30), were administered subcutaneously in rats in pre-treatment with EEIT for the 28-day study.Results: There was increased the AST, ALT, LDH, CPK, and lipid peroxides levels and decreased the TP, SOD, GSH with Isoproterenol-induced group. Pre-treatment for 28 days with Indigofera tinctoria significantly (p<0.05) increased antioxidants (SOD , GSH) , TP levels and decreased the cardiotoxic agents significantly (p<0.05) such as LPO, AST, ALT, LDH, and CPK levels in treatment groups.Conclusion: I. tinctoria contains beneficial bioactive photochemicals that have been protective effective against isoproterenol-induced AMI in rats.

CARDIOPROTECTIVE EFFECT OF INDIGOFERA TINCTORIA LINN. AGAINST MYOCARDIAL INFARCTION-INDUCED RATS

Objective: The aim and objective of the present study are to study the protective effects of ethanolic extract of Indica tinctoria (EEIT) in isoproterenol-induced acute myocardial infarction (AMI) in rats.Methods: The effect of two doses of isoproterenol (5 mg/kg and 8.5 mg/kg body weight) changes in aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), and total protein (TP) and lipid hydroperoxides, superoxide dismutase (SOD), and glutathione (GSH) in blood serum and heart homogenate, for the two consecutive days (29 and 30), were administered subcutaneously in rats in pre-treatment with EEIT for the 28-day study.Results: There was increased the AST, ALT, LDH, CPK, and lipid peroxides levels and decreased the TP, SOD, GSH with Isoproterenol-induced group. Pre-treatment for 28 days with Indigofera tinctoria significantly (p<0.05) increased antioxidants (SOD , GSH) , TP levels and decreased the cardiotoxic agents significantly (p<0.05) such as LPO, AST, ALT, LDH, and CPK levels in treatment groups.Conclusion: I. tinctoria contains beneficial bioactive photochemicals that have been protective effective against isoproterenol-induced AMI in rats.

Cardiac overexpression of perilipin 2 induces dynamic steatosis: prevention by hormone-sensitive lipase

Cardiac intracellular lipid accumulation (steatosis) is a pathophysiological phenomenon observed in starvation and diabetes mellitus. Perilipin 2 (PLIN2) is a lipid droplet (LD)-associated protein expressed in nonadipose tissues, including the heart. To explore the pathophysiological function of myocardial PLIN2, we generated transgenic (Tg) mice by cardiac-specific overexpression of PLIN2. Tg hearts showed accumulation of numerous small LDs associated with mitochondrial chains and high cardiac triacylglycerol (TAG) content [8-fold greater than wild-type (WT) mice]. Despite massive steatosis, cardiac uptake of glucose, fatty acids and VLDL, systolic function, and expression of metabolic genes were comparable in the two genotypes, and no morphological changes were observed by electron microscopy in the Tg hearts. Twenty-four hours of fasting markedly reduced steatosis in Tg hearts, whereas WT mice showed accumulation of LDs. Although activity of adipose triglyceride lipase in heart homogenate was comparable between WT and Tg mice, activity of hormone-sensitive lipase (HSL) was 40–50% less in Tg than WT mice under both feeding and fasting conditions, suggesting interference of PLIN2 with HSL. Mice generated through crossing of PLIN2-Tg mice and HSL-Tg mice showed cardiac-specific HSL overexpression and complete lack of steatosis. The results suggest that cardiac PLIN2 plays an important pathophysiological role in the development of dynamic steatosis and that the latter was prevented by upregulation of intracellular lipases, including HSL.

BENEFICIAL EFFECTS OF ETHANOLIC LEAF EXTRACT OF CORIANDRUM SATIVUM ON METANIL YELLOW INDUCED ALTERATION INACTIVITY OF CATALASE AND LEVEL OF LIPID PEROXIDATION IN HERCINE CARDIAC TISSUE IN VITRO

Objective: The primary aim of the study was to find out a suitable effective dose of metanil yellow that can cause alterations of lipid peroxidation and catalase activity in the heart in vitro and to determine the effectiveness of graded doses of Coriandrum sativum as an antioxidant in preventing lipid peroxidative damage to cardiac tissue and back up catalase activity. Methods: Metanil yellow at different doses (10, 25, 35, 50 µl in phosphate buffer) were applied on isolated hircine heart homogenate (10%) in in vitro followed by estimation of lipid peroxidation and catalase activity after completion of the incubation period. Another set of the experiment included incubation of the heart homogenates with graded dilutions of ethanolic leaf extracts of Coriandrum sativum (CsEth) at concentrations of 10, 20, 30, 40 µl in phosphate buffer medium followed by quantification of the same biochemical parameters as above. This was followed by co-administration of the selected effective dose of metanil yellow (35 µl) and ethanolic leaf extract of Coriandrum sativum (30 µl) on heart homogenate to track the variation in lipid peroxidation and catalase activity in heart homogenate in vitro.Results: Metanil yellow significantly lowered catalase activity in isolated cardiac tissue that was reflected in elevated lipid peroxidation assuming free radical induced oxidative injury to cardiac tissue (p<0.01). However ethanolic leaf extract of Cordiandrum sativum buffered such changes (p<0.01) significantly, presuming a protective action against oxidative cardiac damage.Conclusion: It may be concluded that ethanolic leaf extract of Coriandrum sativum is a promising cardioprotective remedy not only in mitigating free radical mediated lipid peroxidative damage to cardiac tissue but also in reinstating normal catalase activity that may be used an unique herbal based remedy for such cardiac ailments in future.

Protective effects of a new glutamic acid derivative against stress after nNOS blockade

We studied the effects of a new glutamic acid derivative, glufimet, on oxidative stress, activity of antioxidant enzymes, mitochondrial respiration, endothelial vasodilation and anti-platelet activity in female rats after exposure to 24-hour immobilization pain stress and 7-nitroindazole, a neuronal nitric oxide synthase (nNOS) inhibitor. A single dose administration of glufimet (29 mg/kg intraperitoneally) 10 minutes before stress exposure caused a decrease of NO metabolites in serum (by 27.2%) and heart homogenate (33.5% (p£0.05), respectively, compared with the control group. Administration of 7-nitroindazole with glufimet also decreased the studied parameters by 14.3% in the heart homogenate and by 30,3% in the brain (p£0.05) compared with stress exposed rats receiving only the nNOS inhibitor. Glufimet decreased the levels of primary and secondary products of lipid peroxidation (LPO), conjugated dienes by 20% (p£0.05) and 17.3% (p£0.05), ketodienes by 16% and 13.7%, malondialdehyde by 15% (p£0.05) and 26.6% (p£0.05) in the heart and brain mitochondria of stress exposed rats, respectively, compared with the control group. Glufimet administration also increased SOD activity (by 14.4% and 13.1%, respectively), catalase (by 19% and 26.8%, respectively) and glutathione peroxidase (GPx) activity (by 45.5% (p£0.05) and 7.3%, respectively). The antioxidant effect of glufimet may be also attributed to increased coupling between the processes of mitochondria respiration and oxidative phosphorylation. This was evidenced by an increase in the respiratory control ratio (RCR) (by 46.0% (p£0.05) for malate/glutamate and by 49,7% (p£0.05) for succinate) in the heart mitochondria. A statistically significant increase in RCR (by 37.3% (p£0.05)) was observed in stress exposed female rat brain mitochondria for succinate. RCRs differed significantly for succinate in the heart and brain of rats receiving glufimet after nNOS blockade. RCR increased by 62.3% (p£0.05) in the heart mitochondria and by 72.2% (p£0.05) in the brain mitochondria compared with the RCRs in stress exposed rats receiving 7-nitroindazole.

Cardioprotective effect of lemon grass as evidenced by biochemical and histopathological changes in experimentally induced cardiotoxicity

Isoproterenol is a synthetic catecholamine found to cause toxicity leading to severe stress in the myocardium of experimental animals. The aim of the present study is to evaluate the cardioprotective effect of Cymbopogon citratus, which is used as a culinary item and commonly known as lemon grass (LG), in isoproterenol-induced cardiotoxicity. Male Wistar albino rats were segregated into five different groups as follows. Groups I and II rats were treated with vehicle. Groups III and IV rats were treated with 100 and 200 mg/kg b.wt. of LG. Group V with 100 mg/kg b.wt. of vitamin E. Myocardial necrosis was induced in Groups II, III, IV and V on 58th and 59th day using isoproterenol at a dose of 85 mg/kg twice at 24-hour interval. Animals were sacrificed on the 60 th day. LG pretreatment exhibited cardioprotective activity as evidenced by decreased activity of cardiac markers in serum and increased the same in heart homogenate (p < 0.05). LG administration decreased the toxic events of lipid peroxidation (TBARS) in both serum and heart tissue, by increasing the level of enzymatic antioxidants and non-enzymatic antioxidants significantly in both heart homogenate and serum sample (p < 0.05). The histopathological observations also revealed that the cardioprotective effect of LG extract was observed at a dose of 200 mg/kg b.wt. The results of the present study reveal that LG is cardioprotective and antilipid peroxidative by increasing various antioxidants at a dose of 200 mg/kg b.wt., which is comparable with that of vitamin E.

Norepinephrine Transporter is Involved in Down-Regulation of β1-Adrenergic Receptors Caused by Adjuvant Arthritis

Purpose. Inflammation in forms of rheumatoid and experimental arthritis cause not only joint pain but also excessive cardiovascular mortality. The condition also reduces response to calcium channel and β-adrenergic (β1-AR) antagonists. For calcium channel inhibitors, the reduced response is shown to be due to the reduced expression of target proteins. Hydroxymethylglutaryl CoA reductase inhibitors (statins) restore response to propranolol and verapamil. We tested the effect of adjuvant arthritis on the norepinephrine (NE) transporter (NET) density since altered sympathetic nervous system innervation has been observed in rheumatoid arthritis. Methods. Male Sprague–Dawley rats were divided into the following groups: Healthy/Placebo, Healthy/Statin, Pre-AA/Placebo, and Pre-AA/Statin (n=7-8/group). On Day 0, to the Pre-AA and Healthy groups, was injected Mycobacterium butyricum or saline, respectively. On Days 4-8, Statin and Placebo groups received either pravastatin (6 mg/kg) or placebo twice daily, respectively. On day 8, heart and blood samples were collected. The density of NET and 1-AR in heart homogenate; NE in plasma and heart and inflammatory mediators (nitrite and interferon-γ) in serum were determined. Results. Inflammation was associated with a significant reduction in both β1-AR and NET density with a positive correlation between the two proteins (r=0.978, p