Isoproterenol-induced Myocardial Infarction In Rats Research Articles

Attenuation of lipid metabolic abnormalities, proinflammatory cytokines, and matrix metalloproteinase expression by biochanin-A in isoproterenol-induced myocardial infarction in rats

In the present study, we assessed the therapeutic potential of Biochanin-A (BCA) (10 mg/kg BW/day) pretreatment for 30 days on lipid metabolic abnormalities, proinflammatory cytokines and matrix metalloproteinase expression in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. We measured the potential role of BCA on tissue and circulatory lipid profiles as well as on lipid metabolic enzymes: serum inflammatory cytokines (TNF-α, IL-1α, IL-1β, IL-6 and MCP1) and serum Matrix Metalloproteinases (particularly, MMP-2 and MMP-9) together with mRNA expressions of TNF-α, IL-6, MMP-2 and MMP-9 by RT-PCR analysis. Administration of ISO to rats significantly distorted their lipid metabolism and augmented inflammatory process, MMP expression and proteolytic activity. In addition, pretreatment with BCA of ISO-induced MI rats significantly reestablished the altered lipid metabolism and concealed the inflammation of cytokines. BCA suppressed the expressions of proinflammatory cytokines and MMPs in ISO-induced MI in rats when compared to normal untreated MI rats. Hence, these results established that BCA could improve the pathological processes of myocardial remodeling which was confirmed by histopathology of heart in MI rats and might be an effective beneficial ingredient for the management of heart failure disorders.

Protective effects of myrrh essential oil on isoproterenol-induced myocardial infarction in rats through antioxidant, anti-inflammatory, Nrf2/HO-1 and apoptotic pathways

Ethnopharmacological relevanceMyrrh, a traditional remedy, is the stem resinous exudate of Commiphora molmol Engler (Burseraceae). The aromatic yellowish-brown oleoresin has a long history in folk and traditional medicine, in Saudi Arabia and the Arab world. Severe universal concern attributable to the high mortality is Myocardial Infarction (MI). Acute administration of Isoproterenol (ISO) is an established animal model to induce myocardial injury. ObjectiveThe existing animal study was outlined to inspect the actions of Myrrh essential oil on cardiac functional, antioxidant status, apoptotic and inflammatory deviations in isoproterenol induced MI. Materials and methodsNormal and Myrrh control animals were administered normal saline and Myrrh essential oil for thirty days orally, respectively. On the 29th and 30th day, the animals were injected by saline (s.c.). In the ISO control, the animals were administered saline orally for 30 days and then confronted with ISO (85 mg/kg s.c.) on 29th and 30th days. In the Myrrh Groups (IV and V), the animals were treated with Myrrh essential oil (50 and 100 mg/k) respectively for 30 days and injected with ISO (85 mg/kg, s.c.) on 29th and 30th days. ResultsAnimals experienced MI displayed functional blood pressure deviations, intensification in the heart to body weight ratio, myocytes indicative markers (CK-MB, CPK, LDH, cTnT, cTnI), lipid peroxidation (MDA), protein expression of Nrf2 and HO-1, apoptotic markers (Caspase 3,9), and inflammatory indicators. Conversely, animals pre-treated with Myrrh revealed obliteration of those elevations triggered by ISO induction, diminished elevated biochemical values and improved heart function. Conclusion: Myrrh abstain effective cardio-protective action in MI model through improving the oxidative condition with myocytes and abolishing apoptotic as well as inflammatory responses.

Cardioprotective effect of hydroalcoholic leaf extract of Jatropha mollissima on isoproterenol-induced myocardial infarction in rats

We aim to explore various effects of doses of Jatropha mollissima against isoproterenol-induced myocardial infarction in the rat. Rats were divided into 6 groups (10 rats in each). Group-1 was normal to control, and Group-2 was considered intoxicated isoproterenol (ISP) (100 mg/kg, s. c.) Group-3 was treated with standard drug carvedilol, while Group-4, 5, and 6 were treatment groups and treated with J. mollissima extract at the doses of 400, 600, and 800 mg/kg, respectively. Preliminary phytochemistry, histopathological variation in the myocardium, antioxidant potential, and cardiac biomarkers (serum glutamic oxaloacetic transaminase, triglyceride, 2,4,6-trinitrotoluene, serum glutamic pyruvic transaminase, lactate dehydrogenase, and creatine kinase muscle–brain fraction), cardiac rate, electrocardiographing, and pressurization rate index were estimated. This study indicates that the extract proved to have cardioprotective potential and significantly reduced the cardiac biomarkers in a dose-dependent fashion because of flavonoid contents and antioxidant property. The histopathological analysis shows marked improvement in J. mollissima groups handled in comparison with ISP. The present evaluation suggests that J. mollissima has exceptional cardioprotective potential contrary to toxicity caused by isoproterenol. We recommend further studies at the molecular level to frame the exact mechanism of action.

Nootkatone attenuates myocardial oxidative damage, inflammation, and apoptosis in isoproterenol-induced myocardial infarction in rats

BackgroundMyocardial infarction (MI) is a lethal manifestation of cardiovascular diseases. Oxidative stress, inflammation, and subsequent cell death are known to play crucial roles in the pathogenesis of MI. Despite tremendous developments in interventional cardiology, there is need for novel drugs for the prevention and treatment of MI. For the development of novel drugs, usage of natural products has gained attention as a therapeutic approach for ischemic myocardial injury. Among many popular plant-derived compounds, Nootkatone (NKT), a natural bioactive sesquiterpene, abundantly found in grapefruit, has attracted attention for its plausible health benefits and pharmacological properties. PurposeThe present study investigated the cardioprotective effects of NKT in rats against MI induced by isoproterenol (ISO), a synthetic catecholamine and β-adrenergic agonist that produces MI in a physiologically relevant manner. MethodsMI was induced in male Wistar albino rats by subcutaneous injection of ISO (85 mg/kg body weight) on 9th and 10th day. Rats were pre- and co-treated with NKT (10 mg/kg) through daily oral administration for eleven days. ResultsISO-induced MI was characterized by a significant decline in cardiac function, increased serum levels of cardiomyocyte injury markers, enhanced oxidative stress, and altered PI3K/Akt and NrF2/Keap1/HO-1 signaling pathways. ISO also elevated the levels of myocardial pro-inflammatory cytokines, promoted lysosomal dysfunction, altered TLR4-NFκB/MAPK signaling, and triggered intrinsic apoptotic pathway in heart tissues. However, NKT administration significantly restored or modulated majority of the altered biochemical and molecular parameters in ISO-treated rats. Furthermore, histopathological observations confirmed the myocardial restoring effect of NKT. ConclusionThe present study concludes the cardioprotective effects and underlying mechanisms of NKT against ISO-induced MI in rats, and suggests that NKT or plants containing NKT could be an alternative to cardioprotective agents in ischemic heart diseases.

English

The present study was designed to investigate the cardioprotective effect of animal grade piperazine citrate on isoproterenol-induced myocardial infarction in rats by studying cardiac marker enzymes and histopathological changes of the cardiac muscle. Isoproterenol administration showed significant (P<0.001) increase in the serum levels of cardiac injury markers (creatine kinase-MB and troponin-I), 358.98 ± 7.68 iu/l and 13.16 ± 0.35 ng/ml compared to the normal control group of 291.58 ± 3.56 iu/l and 9.66 ± 0.20 ng/ml respectively. Pretreatment with 15 and 30 mg/kg body weight of piperazine citrate showed a decrease in the troponin-I levels when compared with the isoproterenol group; 13.16 ± 0.35 to 12.39 ± 0.22 ng/ml in the group that received 15 mg/kg piperazine citrate (p = 0.0881) and 13.16 ± 0.35 to 11.79 ± 0.30 ng/ml (p = 0.0132) in case of the group pretreated with 30 mg/kg piperazine citrate. With regards to CK-MB, the treated groups with piperazine citrate 15 and 30 mg/kg body weight showed a reduction in the values, 340.76 ± 5.10 (p = 0.0763) and 344.17 ± 8.24 iu/l (p = 0.2178) respectively, compared to the isoproterenol group value of 358.98 ± 7.68 iu/l. Histopathological investigation showed that there was no significant architectural changes in the normal control group that received only normal saline. Structural aberrations caused by isoproterenol were also significantly reduced in the piperazine citrate treated groups. Therefore, the results of the present study suggest that low dose piperazine citrate has a significant effect on the protection of the heart. Key words: Piperazine citrate, myocardial infarction, histopathology, Wistar rat.

Cardioprotective Role of Theobroma cacao against Isoproterenol-Induced Acute Myocardial Injury.

Antioxidants are beneficial in myocardial infarction (MI). It is suggestive that Theobroma cacao (TC) with rich antioxidant properties can be of health benefits in myocardial injury. The study investigated the effect of Theobroma cacao on cardioprotection in isoproterenol-induced myocardial infarction in rats. Male Wistar rats divided into four groups of 6 rats were used for the study. In group 1, 0.9% normal saline placebo was administered via oral gavage to the control. Group 2 was the MI induced group that was given 100 mg/kg body weight isoproterenol subcutaneously twice at an interval of 24 hours. Group 3 was administered TC for 2 weeks at 100 mg/kg bodyweight via the oral route. Group 4 was pretreated with TC (100 mg/kg) via oral route for 2 weeks, immediately followed by the administration of 100 mg/kg body weight isoproterenol subcutaneously twice at an interval of 24 hours. The rats were sacrificed using chloroform anesthesia, and blood samples collected via cardiac puncture. The serum was analyzed for troponin level, lactate dehydrogenase (LDH), and malondialdehyde (MDA) level. The serum troponin, LDH, and MDA levels were found to be significantly (p<0.01) increased in the MI group compared with the control. Pretreatment with TC before MI induction significantly (p<0.01) prevented increased serum troponin, LDH, and MDA levels when compared with the MI group. There was also a significant (p<0.01) decrease in MDA in the TC group compared with the control. These results suggest that Theobroma cacao protects against isoproterenol-induced myocardial injury, possibly by preventing oxidative stress and consequent lipid peroxidation.

Possible Effect of Abscisic Acid on Nitric Oxide in Isoproterenol-Induced Myocardial Infarction in Rats.

The aim of this study was to find out the possible role nitric oxide (NO) due to its nature as a second messenger in stress responses in the cardioprotective effect of the abscisic acid (ABA) in isoproterenol (ISO) -induced myocardial infarction in rats. Material and method: Thirty male rats distributed into: normal control group, myocardial infarction (MI) group, and MI group treated with ABA for one week. The cardiac effect of ABA on ISO-induced MI was evaluated by ECG, measuring mean arterial pressure, markers of heart injury in serum, levels of lipid peroxidation, and antioxidants in heart tissue, observing pathological changes of tissue, and indirect detection of NO was performed. Results: Compared with the MI group, it was found that ABA could ameliorated ISO-induced disturbances in the ECG pattern and in mean arterial pressure. Moreover, the concentration of creatine kinase MB (CK-MB), lactate dehydrogenase (LDH), troponinI (CTn-I), nitrite and nitrate in the serum all decreased in the MI+ABA group. The activities of catalase (CAT), and the content of reduced glutathione (GSH) in heart increased, on the contrary, the content of malondialdehyde (MDA) and iNOS was decreased. In addition, the histopathologic examination showed that pathological changes in the myocardium that was observed in the MI group, was reduced in the group treated with ABA. Conclusion: ABA protected myocardium against damage caused by an ISO through inhibition of lipid peroxidation, prevent the cytotoxic actions of the excessive NO release, and restored near normal architecture and function of myocardial.

The role of 5-HT7 receptors on isoproterenol-induced myocardial infarction in rats with high-fat diet exacerbated coronary endothelial dysfunction.

The presence of 5-HT7r's in both human and rat cardiovascular and immune tissues and their contribution to inflammatory conditions prompted us to hypothesize that these receptors contribute in acute myocardial infarction (MI) with underlying chronic endothelial dysfunction. We investigated the role of 5-HT7 receptors on heart tissue that damaged by isoproterenol (ISO)-induced MI in rats with high-fat diet (HFD). In vitro and in vivo effects of 5-HT7r agonist (LP44) and antagonist (SB269970) have been investigated on the H9C2 cell line and rats, respectively. For in vivo analyses, rats were fed with HFD for 8 weeks and after this period ISO-induced MI model has been applied to rat. To investigate the role of 5-HT7r's, two different doses of LP44 and SB269970 were evaluated and compared with standard hypolipidemic agent, atorvastatin. In vitro studies showed that LP44 has protective and proliferative effects on rat cardiomyocytes. Also in in vivo studies stimulating 5-HT7r's by LP44 improved blood lipid profile (decreased total cholesterol, low-density lipoprotein-C, and triglyceride, increased high-density lipoprotein), decreased cardiac damage markers (creatine kinase and troponin-I), and corrected inflammatory status (tumor necrosis factor-α, interleukin-6). Our results showed significant improvement in LP44 administered rats in terms of histopathologic analyses. In damaged tissues, 5-HT7 mRNA expression increased and agonist administration decreased this elevation significantly. We determined for the first time that 5-HT7r's are overexpressed in ISO-induced MI of rats with underlying HFD-induced endothelial dysfunction. Restoration of this overexpression by LP44, a 5-HT7r agonist, ameliorated heart tissue in physiopathologic, enzymatic, and molecular level, showing the cardiac role of these receptors and suggesting them as future potential therapeutic targets.

Ageratum conyzoides L. Protects rat myocardium during isoproterenol-induced myocardial infarction in rats: A biochemical study

This study aimed to evaluate the preventive effect of Ageratum conyzoides L. on cardiac Troponin T (cTnT), lactate dehydrogenase (LDH)-isoenzyme, cardiac marker enzymes, blood glucose, total proteins, albumin/globulin (A/G) ratio, serum uric acid, serum iron, and plasma iron binding capacity in isoproterenol (ISO)-induced myocardial infarction (MI) in male Wistar rats. Rats treated with ISO(85 mg/kg, administered subcutaneously twice at an interval of 24 h for 2 days) showed a significant increase in the degrees of cardiac troponin T (cTnT), the intensity of the bands of LDH1 and LDH2, and the activities of cardiac diagnostic marker enzymes such as creatine kinase-MB (CK-MB), creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST) and alanine transaminase (ALT) in serum with a subsequent decrease in the activities of CK, LDH, AST and ALT in the heart. ISO-induced rats showed a significant increase in blood glucose, serum uric acid, and serum iron and a decrease in the levels of total proteins, A/G ratio, and iron binding capacity. Pre-treatment with A. conyzoides L. (100 and 200 mg/kg) daily for a period of 30 days significantly altered the levels of cTnT, the intensity of the bands of LDH1, and LDH2-isoenzyme and the activities of cardiac marker enzymes, and other biochemical parameters. Thus, A. conyzoides L. possesses a cardioprotective effect in ISO-induced oxidative stress in rats.

Cardioprotective role of Ageratum conyzoides L. on cardiac mitochondrial enzymes during isoproterenol-induced myocardial infarction in rats

The present study is to evaluate the preventive role of Ageratum conyzoides L. on mitochondrial enzymes such as isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), and α-ketoglutarate dehydrogenase (α-KGDH) and respiratory chain enzymes such as NADH dehydrogenase and cytochrome c oxidase in isoproterenol (ISO)- induced myocardial infarction (MI) in male albino Wistar rats. Rats were orally pre-treated with Ageratum conyzoides L. (100 and 200 mg/kg) to ISO-induced rats daily for a period of 56 days. After the treatment, rats were subcutaneously injected with ISO (85 mg/kg) at an interval of 24 h for 2 days. ISO induction also showed a significant (p

Cardioprotective potential of Spinacia oleracea (Spinach) against isoproterenol-induced myocardial infarction in rats

Context Spinacia oleracea is rich in antioxidant phyto-constituents, termed as the natural antioxidant mixture (NAO). Objective This study investigates the cardioprotective effect of an antioxidant-rich extract of Spinacia oleracea (NAOE) and its phytoconstituent rutin in isoproterenol (ISO)-induced myocardial infarction in rats. Methods Rats were treated with NAOE (400 and 800 mg/kg), rutin (50 mg/kg) and the reference drug gemfibrozil (50 mg/kg) daily for 30 days and were administered ISO (85 mg/kg, s.c) on the last 2 days. Results NAOE treatment attenuated the ISO-elevated levels of serum marker enzymes (AST, LDH and CPK), troponin I, total cholesterol, triglycerides, uric acid, CRP, TNF-α, IL-6 and malondialdehyde. It also restored the ISO-skewed ECG and systolic blood pressure, and the ISO-depleted marker enzymes and endogenous antioxidants in all treated rats. Conclusion It may be concluded that NAOE treatment to ISO-challenged rats exhibited significant cardioprotective effect probably due to the potent antioxidant activity of its NAO.

Cardioprotective effects of (E)-4-hydroxy-N'-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide: a newly synthesized coumarin hydrazone against isoproterenol-induced myocardial infarction in a rat model.

The current study was carried out to evaluate the effect of pretreatment and co-treatment with a newly synthesized coumarin hydrazone, (E)-4-hydroxy-N'-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide (hereinafter EK6), against isoproterenol-induced myocardial infarction in rats. Changes in biochemistry, cardiac biomarkers, electrocardiography, and histopathology after treatment with EK6 or acenocoumarol (Sintrom) were studied. Animals were randomly divided into 4 groups: vehicle control (C), isoproterenol + Sintrom (ISO + Sin), isoproterenol + EK6 (ISO + EK6), and isoproterenol (ISO). Myocardial infarction was induced by subcutaneous ISO administration at a dose of 85 mg·kg-1·day-1 with a drug-free interval of 24 h on days 6 and 7. Treatment with ISO led to significant elevation (p < 0.05) in serum levels of cardiac injury biomarkers, namely cardiac troponin-T, lactate dehydrogenase, creatine kinase-MB, alanine aminotransferase, and aspartate aminotransferase compared with levels in the vehicle control. A change in the lipid profile was also observed as a significant increase in total cholesterol and triglycerides. Furthermore, ISO caused significant alterations in the electrocardiogram pattern, including significant ST-segment elevation, significant decreased R wave amplitude, and significant increase in heart rate (16%) as well as marked changes in the histopathology of the heart tissue. Pretreatment and co-treatment with newly synthesized coumarin hydrazone restored all ISO-induced biochemical, lipid, cardiac, and histopathological changes in rats with myocardial infarction.

AMELIORATION OF MYOCARDIAL INJURY IN DIABETIC RATS BY KAEMPFEROL

Objective: Ischemic heart disease is one of the leading causes of global mortality. Reperfusion i.e. restoration of the blood to the ischemic heart is a necessary therapeutic approach to maintain cardiac function. However, reperfusion elicits a series of adverse events that paradoxically cause injury of myocardium. Kaempferol (KMP), a naturally occurring polyphenolic compound which is present in tea, broccoli, propolis and grapefruit and possesses anti-oxidant, anti-inflammatory, anti-apoptotic, anti-cancer, neuroprotective, cardioprotective and anti-diabetic properties. Therefore, Present study, aimed to investigate the effect of kaempferol in ischemia-reperfusion (IR) model of myocardial injury in rats. Design and method: Male albino wistar rats were used for this study. They were divided into sham, IR-control, KMP-20+IR and KMP 20 per se groups. KMP was administered daily to the rats at a dose of 20 mg/kg intraperitoneally for a 15 day period. The dose of KMP was determined by our earlier studies in isoproterenol-induced myocardial infarction in rats. On the 15th day, ischemia was developed by one-stage ligation of left anterior descending coronary artery for 45 minutes followed by reperfusion for 60 minutes. Hemodynamic parameters (systolic and diastolic blood pressures mean arterial pressure, heart rate, left ventricular end diastolic pressure, maximal positive and negative rate of left ventricular pressure) were recorded. Rats were then sacrificed, the heart was excised and processed for biochemical (determination of the levels of MDA, GSH, SOD, catalase, Ck-MB, LDH), morphological (H&E staining and electron microscopy) and molecular studies (western blot analysis, immunohistochemistry and TUNEL assay). Results: KMP pretreatment significantly alleviated IR injury by maintaining cardiac function, attenuating oxidative stress and preserving cardiac morphology. Also, there was a decrease in the level of inflammatory markers (TNF-alpha, IL-6 and NF-kappa-B), inhibition of expression of active JNK and p38 proteins and activation of ERK1/2, a pro-survival kinase. Further, apoptosis was markedly reduced as was evident from decreased expression of pro-apoptotic proteins (Bax and Caspase-3), TUNEL positive cells and increased levels of anti-apoptotic proteins (Bcl-2). Conclusions: KMP safeguards against IR injury by attenuating inflammation and apoptosis through modulation of MAPK pathway and rectification of redox state of the myocardium.

The Effect of Astragaloside IV on Isoproterenol-Induced Myocardial Infarction in Rats

Background: Astragaloside IV (AST) is a saponin from the roots of Astragalus plants which has been widely used in traditional medicine to treat cardiovascular diseases. However, the effect of AST on myocardial infarction remains unknown. Thus, we aimed to investigate the cardio protective effects of AST on isoproterenol-induced myocardial infarction in rats. Methods: AST was isolated from the roots of Astragalus caspicus. Male Wistar rats were assigned to 5 groups of control, isoproterenol, and treatment with 2.5, 5 and 10 mg/kg AST given orally immediately before MI induction. Subcutaneous injection of isoproterenol (100 mg/kg) for two consecutive days was used to induce myocardial infarction. AST was given orally once daily for 4 days. On the fifth day hemodynamic and electrocardiographic parameters were assessed, and serum and tissue samples were used to evaluate histological and biochemical changes. To more assessment of the effects of AST on myocardium, we also used three doses of 0.1, 1 and 2 µM of AST in isolated heart model. In statistical analysis with one-way-ANOVA test, any differences between groups were considered significant at p&lt;0.05. Results: Isoproterenol injection caused ECG abnormality, hemodynamic depression and myocardium damage. While AST administration increased mean arterial blood pressure and heart rate and improved the left ventricular contractility. The peripheral neutrophil count, cardiac enlargement and cardiac ischemia was significantly decreased by AST. Also, histopathological evaluations showed that AST significantly diminished post MI necrosis and fibrosis in heart tissue and inhibited the inflammatory responses. The isolated heart studies hemodynamic factors showed no significant changes. Conclusion: Results showed that AST can protect heart against myocardial infarction by improving cardiac histology and ventricular contractility. Due to the lack of protection in the isolated heart, it is likely that the positive effects are more associated with the improvement of the oxidative stress markers in the systemic circulation, and the absolute effect on the isolated heart does not play an essential role in myocardium protection.

Ursolic acid modulates MMPs, collagen-I, α-SMA, and TGF-β expression in isoproterenol-induced myocardial infarction in rats.

In the present study, the modulatory effect of ursolic acid (UA) on cardiac fibrosis and mitochondrial and lysosomal enzymes activity in isoproterenol-induced myocardial infarction (MI) in rats were examined. Isoproterenol hydrochloride (ISO; 85 mg/kg body weight) was administered subcutaneously for first two consecutive days. ISO-induced MI in rats significantly decreased the activities of mitochondrial tricarboxylic acid cycle enzymes and respiratory chain enzymes while increased the activities of lysosomal glycohydrolases and cathepsins. The expression of matrix metalloproteinase 2 (MMP-2), MMP-9, collagen type I, α-smooth muscle actin (α-SMA), and transforming growth factor-β (TGF-β) were upregulated in ISO-induced MI in rats. UA administration to rats showed increased activities of mitochondrial tricarboxylic acid cycle enzymes and respiratory chain enzymes and decreased activities of lysosomal glycohydrolases and cathepsins in ISO-induced rats. Furthermore, expression of MMP-2, MMP-9, collagen type I, α-SMA, and TGF-β downregulated in UA-administered rats. Thus, our results demonstrate that UA has an anti-fibrotic effect and attenuates the mitochondrial and lysosomal dysfunction in ISO-induced MI in rats.

The Ethanol Leaf Extract of Moringa Oleifera Blunts Isoproterenol‐induced Cardiotoxicity in Rats through Mitigation of Free Radical Production and Down Regulation of Cardiac Troponin and Nuclear Factor Kappa B

Moringa oleifera is a plant that is widely distributed in the tropical environment and is used for medicinal purpose. It is believed that every part of this plant has medicinal value. The study evaluated the effect of the ethanol leaf extract of Moringa oleifera (EMOL) on isoproterenolinduced myocardial infarction in rats. Thirty‐five male Wistar rats weighing between 100 and 160 mg/kg were used for the study. The rats were randomly divided into 5 groups of 7 animals per group. Group A (control) animals were given normal saline, Group B (Toxicant) animals were given 100 mg/kg of isoproterenol administered subcutaneously on day 8. Groups C and D animals were given 50 mg/kg and 100 mg/kg of ethanol leaf extract of Moringa oleifera (ELMO) respectively for 7 days and on day 8 were given 100mg/kg of isoproterenol. Group E animals received 100 mg/kg of Moringa oleifera only for 7 days. On day 9 blood sample was taken for serum analysis of CK‐MB, Myeloperoxidase, Nitric oxide and Total protein, thereafter the animals were sacrificed via cervical dislocation and heart harvested for biochemical assays for the analysis of Advanced oxidative protein product (AOPP), Protein Carbonyl (PC), Malonaldehyde (MDA), Superoxide dismutase (SOD), Glutathione‐S‐Transferase (GST), Reduced glutathione (GSH), Glutathione peroxidase (GPx), Total thiol, Non‐protein thiol and Hydrogen peroxide (H2O2) generation), histopathology and immunohistochemistry (CTnI, NF‐KB).In this study there is significant (p &lt; 0.05) reduction in SOD, GPx, GST, increased AOPP, PC, MDA, MPO levels and H2O2 generation in toxicant group (group B) but there was corresponding increase in the antioxidant enzymes and decrease in markers of oxidative stress and inflammation in ELMO treated groups. The toxicant also caused severe histopathological changes in the heart tissues but these were corrected by all the doses of the extract. There was increase expression of CTnI and NF‐KB in the toxicant group; pre‐treatment with ELMO however caused significant down regulation of all these proteins signifying its anti‐inflammatory and anti‐oxidative property.In conclusion, these experiments showed that ethanol leaf extract of Moringa oleifera possess cardiac protective effect through mitigation of free radicals production and down regulation of the studied cytokines.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The protective impact of betaine on the tissue structure and renal function in isoproterenol-induced myocardial infarction in rat.

BackgroundMyocardial infarction is one of the most common life threatening diseases that may lead to renal disorders via oxidative stress and inflammation. Betaine is a safe and well‐tolerated compound exhibiting beneficial antioxidant and anti‐inflammatory properties. Previous studies have demonstrated protective effects of betaine against myocardial infarction and renal injury. This study aimed to investigate the protective effect of betaine on tissue structure and renal function after isoprenaline‐induced myocardial infarction in rats.MethodsFifty Wistar strain male albino rats, weighing 200 ± 10, were selected for the study. The animals were housed individually under standard environmental conditions (Light–dark cycle, temperature and constant humidity) for 1 week. After acclimatization, they were randomly divided into five groups. G1, G2, and G3 groups received betaine at doses of 50, 150, and 250 mg/kg body weight/day via gavage for a period of 60 days. After 60 days, isoprenaline is injected subcutaneously (200 mg/kg body weight). In the isoprenaline group (G4), the rats were injected with isoprenaline (200 mg/kg body weight) and the control group (G5) received a standard diet (Without isoprenaline). Then, isoproterenol solution was used for induction of myocardial infarction. At the end, the expression of nitric oxide synthase (iNOS) protein was detected using immunohistochemical analysis and kidney tissues were assessed via histopathological analysis. In addition, serum level of TNF‐α and creatinine level were measured via ELISA test and colorimetric methods, respectively.ResultsThe results of our study indicate that isoproterenol‐induced renal histopathological injury without changing creatinine level. Betaine has protective effects against renal injuries induced by isoprenaline and the expression of nitric oxide synthase (nNOS) protein showed no significant difference in all groups. Further, betaine reduced TNF‐α level significantly.ConclusionAccording to our results, betaine has protective effects on isoprenaline‐induced renal failure via a decrease in TNF‐α level and nitric oxide synthase.

Water fraction of Sonchus arvensis (Linn.) leaves protects heart upon isoproterenol-induced myocardial infarction in rats and promotes survival of cardiomyocytes in vitro

Water fraction of Sonchus arvensis (Linn.) leaves protects heart upon isoproterenol-induced myocardial infarction in rats and promotes survival of cardiomyocytes in vitro

Effects of nimodipine, vinpocetine and their combination on isoproterenol-induced myocardial infarction in rats

BackgroundMyocardial infarction (MI) remains a major cause of morbidity and mortality worldwide. Nimodipine is a calcium (Ca2+) channel blocker as well as a PDE1 inhibitor and primarily used in subarachnoid haemorrhage (SAH) due to its blood-brain barrier crossing property. Nimodipine and vinpocetine inhibit the degradation of phosphodiester bond which increases cGMP and cAMP levels causing vasodilation. Material and methodsWe have divided rats randomly into Group I - Vehicle control; Group II - Toxic control (ISO 85 mg/kg, i.p.); Group III, IV and V - Nimodipine (5, 10 and 15 mg/kg, i.p. respectively) with ISO; Group VI- Nimodipine (15 mg/kg) alone; Group VII – Nimodipine + Vinpocetine (10 mg/kg + 10 mg/kg) with ISO; Group VIII - Nimodipine + Vinpocetine (10 mg/kg + 10 mg/kg) alone; Group IX- Diltiazem (25 mg/kg, p.o) with ISO; Group X- Diltiazem (25 mg/kg) alone and Group XI- Vinpocetine (10 mg/kg, p.o.) with ISO for 7 days. After 24 h of the last dose, haemodynamics were assessed then animals were sacrificed and biochemical, histopathological and ultrastructural changes were measured. ResultsTreatment with ISO significantly deviated the haemodynamic parameters (HR, SAP, DAP and MAP), biochemical parameters (CK-MB, LDH, SGOT, cGMP and Troponin-T) and antioxidant markers (TBARS, SOD, CAT, GSH, GPx, GST and GR). Haemotoxylin and eosin staining of the cardiac tissue and ultrastructural study also indicated significant myocardial damage. Pretreatment with nimodipine (10 and 15 mg/kg, i.p), vinpocetine (10 mg/kg, p.o) and their combination significantly restored the antioxidant status, haemodynamic profile, cellular architecture and ultrastructural changes in the heart. ConclusionNimodipine and vinpocetine both showed cardioprotection when given alone. However, their combination showed better restoration in terms of oxidative stress, cardiac membrane damage, haemodynamics, histopathology and ultrastructural changes.

Protective effects of α-bisabolol on altered hemodynamics, lipid peroxidation, and nonenzymatic antioxidants in isoproterenol-induced myocardial infarction: In vivo and in vitro evidences.

The effect of α-bisabolol on hemodyanimcs, lipid peroxidation, and nonenzymatic antioxidants was evaluated in isoproterenol-induced myocardial infarction in rats. They were pre- and cotreated with α-bisabolol (25 mg/kg body weight) daily for 10 days along with the subcutaneous injection of isoproterenol (85 mg/kg body weight) at an interval of 24 hours for 2 days (9th and 10th days). Increased activities of serum creatine kinase and creatine kinase-MB along with altered levels/concentrations of lipid peroxidation products and nonenzymatic status were observed in the plasma and heart tissues of rats. Treatment with α-bisabolol showed protective effects by reversing the altered biochemical parameters and hemodynamics studied. The in vitro reducing power of α-bisabolol confirmed its potent antioxidant action. These biochemical benefits were translated into functional recovery by the maintenance of the hemodynamics in rats. The findings showed that α-bisabolol has the potential to protect against isoproterenol-induced myocardial infarction due to its potent antilipid peroxidation and antioxidant properties.