Isoproterenol-induced Myocardial Infarction Research Articles

Protective effects of silver nanoparticles in isoproterenol-induced myocardial infarction in rats.

BackgroundSilver nanoparticles (AgNPs) are widely used in the medical field, including cardiovascular. However, limited research has investigated the effect of AgNPs on the protection of myocardial infarction (MI).ObjectivesIsoproterenol (Iso)-induced MI and the cardiac protection offered by AgNPs were investigated in the present study. Additionally, we characterized the profile of Ag in the form of nanoparticles.MethodsTwenty-four male Wistar rats were randomly divided into four groups as follows: normal, Iso, Iso + AgNO3, and Iso + AgNP groups. AgNPs and silver ion (AgNO3) were administered intraperitoneally at 2.5 mg/kg BW for 14 days. Iso induction was performed using two doses of 85 mg/kg BW given subcutaneously on days 13 and 14. Blood and cardiac tissue samples were taken 24 h after the last dose of Iso and checked for Creatine Kinase-MB (CK-MB), lactate dehydrogenase in plasma along with oxidative stress parameters, mitochondria biogenesis markers, and inflammation representative genes in cardiac tissue. Additionally, we analyzed the histopathological features in cardiac tissue.ResultsThe silver was confirmed in the form of nanoparticles by its size at intervals of 8.72–37.84 nm. Both AgNO3 and AgNPs showed similar cardioprotective effects, as shown by the decrease in biochemical markers of cardiac toxicity, namely, CK-MB. Additionally, AgNPs group have better efficacy compared with AgNO3 group in ameliorating Iso-mediated oxidative stress production, as evidenced by the significant decrease in malondialdehyde level and increased superoxide dismutase activity (P < 0.0001 and P < 0.01, respectively) in cardiac tissue compared with the Iso group. Mechanistically, AgNPs, but not AgNO3, enhanced the expression levels of mitochondrial transcription factor A and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha in post-MI heart and reduced the protein expression of nuclear factor-kappa B (NF-κB) assessed by western blot analysis. Furthermore, these results were confirmed with the histopathological evaluation of cardiac tissue. Nevertheless, pretreatment with either AgNO3 or AgNPs improved the aspartate aminotransferase level.ConclusionThese results suggested that AgNPs have more superior cardioprotective effect compared with AgNO3 against Iso-induced MI, at least in part through amelioration of NF-κB expression level induced by oxidative stress overproduction.

D‐pinitol attenuates isoproterenol‐induced myocardial infarction by alleviating cardiac inflammation, oxidative stress and ultrastructural changes in Swiss albino mice

Cardiovascular diseases are the most disturbing problems throughout the world. The side effects of existing drugs are continuously compelling the scientist to look for better options in terms of safety, efficacy and cost-effectiveness. Our study is also a move in this direction. We have chosen D-pinitol to see its cardioprotective role in isoproterenol-induced myocardial infarction in Swiss albino mice. Grouping was made by dividing mice into eight groups (n=6). Group I, control; Group II, isoproterenol (ISO) (150 mg/kg, i.p.); Group III, D-pinitol (PIN) (25 mg); Group IV, PIN (50 mg); Group V, PIN (100 mg) per kg per oral, respectively with ISO; Group VI, PIN per se (100 mg D-pinitol only); Group VII, Propranolol (PRO) (20 mg/kg/oral) with ISO; and Group VIII, PRO per se (20 mg/kg, p.o.). After 24 h of the last dose, the blood sample was collected for biochemical parameters, then mice were, killed through cervical dislocation under anaesthesia and cardiac tissue was collected for biochemical, histopathological and ultrastructural evaluation. Administration of ISO in mice altered the level of antioxidant markers, cardiac injury markers and inflammatory markers, which were significantly restored towards normal by D-pinitol at the dose of 50 and 100 mg. 25 mg of D-pinitol dosage, did not produce significant cardio protection. The histopathological and ultrastructural analysis further confirmed these findings. Our study showed that D-pinitol significantly protected myocardial damage which was induced by ISO and reverted oxidative stress and inflammation considerably.

Combined Antioxidant Formulation of Ascorbic Acid with Resveratrol Ameliorates Isoproterenol-Induced Myocardial Infarction in Rats

The current investigation was proposed to assess the effectiveness of the combination of resveratrol and ascorbic acid against Isoproterenol (ISO)-induced myocardial infarction in rats. The experimental model was divided into six groups (n = 6 in each group). Group I: control, Group 2: isoproterenol (ISO)-100 mg/kg b.wt, Group 3: ISO+Resveratrol (RES) (20 mg/kg b.wt) treated, Group 4: ISO+ Ascorbic acid (AA) (80 mg/kg b.wt) treated, Group 5: ISO+RES (20 mg/kg b.wt)+AA (80 mg/kg b.wt) treated and Group 6 : RES (20 mg/kg b.wt)+ AA (80 mg/kg b.wt) alone treated. The study showed an increase in lipid peroxides and cardiac markers in the serum samples of experimental animals administered with ISO. Treatment with RES and AA individually and a combinational formulation brought a significant decrease in lipid peroxides and cardiac markers. They increased the level of enzymatic antioxidants and non-enzymatic antioxidant levels. Histopathological results showed the distortion of heart architecture among the experimental groups administered with ISO and significant recovery when treated with RES and AA individually and in their combination. The study presents the effective combination of RES and AA in combating ISO-induced myocardial infarction and protection against ROS-mediated oxidative stress.

Crassocephalum rubens extract and fractions: Hypolipidemic and cardioprotective activities

Globally, cardiovascular diseases are becoming the major cause of death. Crassocephalum rubens is an indigenous vegetable used traditionally in the treatment of several disease conditions including stomach upset, wounds, and high blood pressure. However, there are limited literature reports on its hypolipidemic and cardioprotective activities, hence this study investigated the effects of leaf methanol extract and fractions of C. rubens on lipid profile, liver, cardiac marker enzymes; alanine (ALT), and aspartate (AST) aminotransferases, and cardiac tissue integrity in Isoproterenol-induced myocardial infarction (MI) in rats. Forty-five male Wistar rats were randomly divided into nine groups and administered different doses (100 &amp; 150 mg/kg) of the plant extract and fractions for 14 days while normal control and MI control received phosphate buffer saline. C. rubens leaf methanol extract and fractions significantly (p&lt;0.05) reduced TC (75.45 ± 2.44 - 96.09 ± 1.65 mg/dL), TG (84.04 ± 1.79 - 127.00 ± 0.47 mg/dL), VLDL-C (16.81 ± 0.36 - 25.42 ± 0.10 mg/dL), LDL-Cholesterol (03.49 ± 1.03 - 26.04 ± 1.64 mg/dL), and AST of the pretreated myocardial infarcted rats versus MI control (168.70 ± 9.85 mg/dL, 146.60 ± 1.74 mg/dL, 29.31 ± 0.34 mg/dL, 77.73 ± 9.67 mg/dL, respectively), while plasma HDL-C was increased. The crude extract and fractions of C. rubens showed significant cardioprotective activities on the integrity of the heart tissues of the experimental rats. The findings reveal antihyperlipidemic and cardioprotective potentials and provide a possible lead for isolation of bioactive compounds from C. rubens in the management of hyperlipidemia and its associated ailments.

Bergenin from Bergenia Species Produces a Protective Response against Myocardial Infarction in Rats

Bergenin is a phenolic glycoside that has been reported to occur naturally in several plant species, reported as a cardioprotective. However, bergenin, one of the important phytochemicals in these plants, is still not reported as a cardioprotective. The present study was designed to investigate the cardioprotective effects of bergenin on isoproterenol-induced myocardial infarction in rats. Bergenin and atenolol were administered through intraperitoneal (i.p.) injection to Sprague Dawley (SD) rats in separate experiments for five (5) days. At the end of this period, rats were administered isoproterenol (80 mg/kg s.c.) to induce myocardial injury. After induction, rats were anaesthetized to record lead II ECG, then sacrificed, blood was collected to analyze cardiac marker enzymes, and a histopathological study of the heart tissues was also performed. Pretreatment with bergenin showed a significant decrease in ST-segment elevation, deep Q-wave, infarct size, and also normalized cardiac marker enzymes (cTnI, CPK, CK-MB, LDH, ALT, and AST), particularly at 3 mg/kg, as compared to isoproterenol treated group. Our findings revealed, for the first time, the use of glycoside bergenin as a potential cardioprotective agent against the isoproterenol-induced MI in rats.

Effect of Fraxetin on Oxidative Damage Caused by Isoproterenol-Induced Myocardial Infarction in Rats.

At present, cardiovascular disorders are the most prominent factors for the high morbidity rate globally. The occurrence of myocardial infarction followed by myocardial ischemia is the important cause of high death rates. Various medical treatments are available, yet the mortality and morbidity rate is high. In the present investigation, the cardioprotective property of fraxetin (Fx) is evaluated in myocardial infarction-induced experimental rats. Fraxetin, a phytochemical known as coumarin isolated from Fraxinus rhynchophylla. Fraxetin has numerous pharmacological activities including antioxidant, apoptosis inhibitor, anti-inflammatory, and antimicrobial agent. The experimental mice were split into 4 groups each comprising six animals. Group I was considered the control group; 0.1% NaCl solution was given as dosage. Group II received only Fx; group III was treated with ISO. Group IV was treated with Fx followed by ISO to induce myocardial infarction. In ISO administrated rats, there were changes in the heart weight, activities of cardiac markers, transmembrane protein activity, antioxidant enzymes, pro-inflammatory proteins, lipid profile, and myocardial structures. Pre-treatment of fraxetin in group IV experimental rats resulted in decreased cardiac weight, diminished level of cardiac markers (cardiac troponin T (cTnT), creatine kinase, creatine kinase-MB, and cardiac troponin I (cTnI)), reduced level of oxidative stress biomarkers (LOOH and TBARS) in the plasma and cardiac tissue, amplified level of enzymes in antioxidant defense system (catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GPx)) in the plasma and heart tissue, and elevated level of ATPase activities. The histopathological studies also revealed the potent activity of fraxetin in protecting the cardiac tissues from inflammation and damage. ISO-administrated experimental rats treated with fraxetin exhibit increased antioxidants activity and decreased free radicals. Our study revealed that the administration of fraxetin significantly reduced the extent of myocardial damage during myocardial infarction in rats caused by isoproterenol. Thus, the results prove the cardioprotective effect of fraxetin in MI-induced rats.

Protective Effect of Silymarin and Boric Acid Against Isoproterenol-Induced Myocardial Infarction in Mice

This study aimed to compare the protective or therapeutic effects of silymarin and/or boric acid against myocardial infarction induced by isoproterenol. Distilled water was given orally by gavage to the GI and GII groups for fourteen days. The GIII group was received silymarin (100mg/kg), while the GIV group was given boric acid (100mg/kg) for 14 days. In the last group, both silymarin and boric acid were given orally (gavage) for fourteen days. On the thirteenth and fourteenth days of the study, while isotonic water was applied to the GI group, isoproterenol (85mg/kg) was applied to the other groups subcutaneously. Plasma ALT, AST, Ca, CK, CHO, TP, Ing P, IL-6, IL-12, PAL-1, and sPLA2 parameters were evaluated. Histopathological examination was performed on the heart, lung, liver, kidney, spleen, cerebrum, and cerebellum tissues taken from mice. The CK level was found to be significantly lower in the GIII and GV groups compared to the GII group (P

Cardio protective activity of Sargassum wightii on isoproterenol induced myocardial stress in rats

The aim of this investigation is to determine whether the methanolic extracts of Sargassum wightii can protect rats against isoproterenol-induced myocardial infarction. Four different groups of rats (6 rats in each group) were taken; where group 1 comprised of normal untreated rats, group 2 was injected with Isoproterenol (synthetic catecholamine), group 3 was considered as standard and hence, was injected with Isoproterenol + Simvastatin and group 4 was treated with Isoproterenol + Sargassum wightii’s extract. Cardioprotective effects of Sargassum wightii was observed via the changes in the lipid profile, cardio marker enzymes and through histopathological studies. Rats treated with the extract of S. wightii showed a significant reduction in total cholesterol, LDL-cholesterol, serum triglycerides and increase in HDL- cholesterol level indicating an undamaged myocardial membrane. Likewise, low enzyme activity in Sargassum wightii treated rats clearly indicated the cardioprotective effects of Sargassum wightii. Histopathological studies were also done to observe the changes on the rats at the tissue level and no pathological changes were observed in Sargassum wightii treated rats. Hence, methanolic extract of Sargassum wightii is evidenced to possess cardioprotective activity against myocardial infarction.

Combinatorial Delivery of Cinnamaldehyde and Quercetin Ameliorates Isoproterenol-Induced Cardiac Inflammation, Apoptosis and Myocardial Infarction via Modulation of NF-kB P65 and Cleaved Caspase-3 Signaling Molecules in Wistar Rats

Combinatorial Delivery of Cinnamaldehyde and Quercetin Ameliorates Isoproterenol-Induced Cardiac Inflammation, Apoptosis and Myocardial Infarction via Modulation of NF-kB P65 and Cleaved Caspase-3 Signaling Molecules in Wistar Rats

Potential cardioprotective effect of octreotide via NOXs mitigation, mitochondrial biogenesis and MAPK/Erk1/2/STAT3/NF-kβ pathway attenuation in isoproterenol-induced myocardial infarction in rats

Myocardial infarction (MI) is a global health care problem, which instigates irreversible cardiac tissue damage and sudden death, necessitating new prevention and management strategies. Hence, the cardioprotective effect of octreotide in MI was scrutinized by tackling the possible underlying trajectories involved. Isoproterenol (ISO)-induced acute MI model was adopted using ISO (85 mg/kg/day, S.C.) for 2 days. Rats in octreotide groups were pretreated with 20 or 40 μg/kg/day S.C. for 8 days and ISO was given on the 7th and 8th days. Octreotide showed a restoration of ECG changes, cardiac hemodynamics abnormalities, serum cardiac markers elevation (creatine kinase MB, troponin I, lactate dehydrogenase, and aspartate aminotransferase), and cardiac histoarchitecture abnormalities. In addition, octreotide pretreatment showed a significant increase in the cardiac and serum level of the diagnostic microRNA-133a. Octreotide attenuates oxidative stress indices (MDA, GSH, SOD, TAC, and HIF-1α), besides a better adjustment of NOX-1/-2/-4 expression and protein levels. Mitochondrial morphology and mtDNA copy number were preserved following the pre-treatment of Octreotide. The inflammatory pathway p38 MAPK/Erk-1/-2/p-STAT3/NF-κB pathway and the proinflammatory cytokines (TNF- α, IL-6, and IL- 1β) were attenuated. The proapoptotic markers (cyt c, caspase-3/-9, and Bax) were also attenuated and the antiapoptotic Bcl2 marker was increased by the preadministration of octreotide. In almost all parameters, Octreotide 40 μg/kg/day was more prominent than its lower dose. Octreotide possesses dose-dependent cardioprotective properties via its antioxidant, anti-inflammatory, and anti-apoptotic capabilities.

Curcumin Protects Diabetic Mice against Isoproterenol-Induced Myocardial Infarction by Modulating CB2 Cannabinoid Receptors.

Molecular docking revealed curcumin as a potent CB2 cannabinoid receptor (CB2R) agonist. Since CB2R is involved in cardioprotective functions, we explored its role in ameliorative actions of curcumin against myocardial damage triggered by isoproterenol in diabetic animals. Mice were kept on a high-fat diet (HFD) throughout the experiment (30 days). Following 7 days of HFD feeding, streptozotocin was administered (150 mg/kg, intraperitoneal) to induce diabetes. From day 11 to 30, diabetic mice received either curcumin (100 or 200 mg/kg/day, oral), CB2R antagonist AM630 (1 mg/kg/day, intraperitoneal) or both, with concurrent isoproterenol (150 mg/kg, subcutaneous) administration on day 28 and 29. Diabetic mice with myocardial infarction showed an altered hemodynamic pattern and lipid profile, reduced injury markers, antioxidants with increased lipid peroxidation in the myocardium, and elevated glucose and liver enzymes in the blood. Moreover, an increased pro-inflammatory markers, histological severity, myonecrosis, and edema were observed. Curcumin compensated for hemodynamic fluctuations, restored biochemical markers, preserved antioxidant capacity, decreased cytokines levels, and restored cardiac functionality. However, the AM630 pre-treatment attenuated the effects of curcumin. The data suggest the involvement of CB2R in the actions of curcumin such as in the prevention of myocardial stress and in the improvement of the normal status of the myocardial membrane associated with diabetes.

Inhalation of PM2.5 from diesel exhaust promote impairment of mitochondrial bioenergetics and dysregulate mitochondrial quality in rat heart: implications in isoproterenol-induced myocardial infarction model

Aim: Ambient exposure of PM2.5 from diesel exhaust (termed as diesel particulate matter [DPM]) can induce cardiotoxicity that can be manifested into myocardial ischemia/infarction, where the survival depends on mitochondrial function. The mechanism for DPM-induced mitochondrial dysfunction is yet to be elucidated and the consequential impact of impaired mitochondria on the severity of myocardial infarction (MI) has not been established. Materials and methods: Female Wistar rats were exposed to DPM (0.5 mg/ml) for 3 h daily (to achieve a PM2.5 concentration of 250 µg/m3) for 21 d trailed by an induction of MI using isoproterenol (ISO). Conclusion: DPM exposure altered the basal ECG pattern and increased heart weight (HW) to body weight (BW) ratio from control. Loss of mitochondrial quality in the cardiac tissue was observed in DPM exposed animals, measured via declined ETC enzyme activity, reduced ATP levels, high oxidative stress, low mitochondrial copy number, and low expression of the mitochondrial genes involved in mitophagy (PINK and PARKIN) and mitochondrial fusion (MFN-1). Subsequent induction of MI in DPM exposed animals (DPM + ISO) further deteriorated the normal sinus rhythm, accompanied by elevated plasma CK and LDH level, increased myocardial caspase activity, downregulation of Peroxisome proliferator-activated receptor-gamma coactivator (PGC1-α), transcription factor A (TFAM), DNA polymerase subunit gamma (POLG), and other mitochondrial quality control genes. Based on these results, we conclude that DPM alters the electrophysiology and ultrastructure of the heart that aggravates the MI-induced cardiotoxicity, where the diminished mitochondrial quality can be the potential contributor.

Metabolomics analysis delineates the therapeutic effects of hydroethanolic extract of Cucumis sativus L. seeds on hypertension and isoproterenol-induced myocardial infarction

Cucumis sativus L., widely cultivated as an edible vegetable. Its seeds are well reputed for cardiovascular preventive properties. However, the mechanisms underlying for cardiovascular protection of C. sativus are still unidentified. Therefore, this study utilized a metabolomics approach to investigate putative mechanisms of C. sativus seeds in myocardial infarction (MI) and in vitro models of vasoconstriction, atrium, and invasive blood pressure measurement. Results showed that Cu.EtOH extract showed a vasorelaxant response with potent hypotensive effect in normotensive rats and L-NAME induced hypertension. Cu.EtOH caused a negative inotropic and positive chronotropic effect on the atrium. Cu.EtOH protected the animals from ISO-induced myocardial infarction (MI) interventions in left ventricular thickness, cardiomyocyte hypertrophy, mRNA gene expression, and biochemical assays. The metabolomics data suggested that Cu.EtOH mainly affected amino acid metabolism, BCAA degradation, ketone bodies degradation, and oxidative stress. Our study showed that Cu.EtOH suppressed inflammation with a strong anti-myocardial infarction impact. Additionally, our findings indicated Cu.EtOH reverted the amino acid metabolism, BCAA, and ketone bodies degradation. The findings show the antihypertensive mechanism of Cu.EtOH may include the modulation of endothelium-derived relaxing factor (EDRF) produced from nitric oxide (NO) and is connected with vascular endothelial function. C. sativus seeds, in particular, played a pivotal role in the treatment of myocardial and vascular disorders by enhancing the EDRF mechanism, energy generation, and antioxidant capacity. In summary, our findings showed the mechanistic insights on the therapeutic potential of C. sativus seeds for cardiovascular disorders.

Vasorelaxant and Antioxidant Effects of Aframomum pruinosum Gagnep. (Zingiberaceae) Seed Extracts May Mediate Their Cardioprotective Activity against Isoproterenol-Induced Myocardial Infarction.

Aframomum pruinosum seeds are traditionally used in Cameroon to treat cardiac palpitations. The present work evaluates the cardioprotective effects of the aqueous (AE) and ethanolic (EE) extracts from A. pruinosum seeds against isoproterenol-induced myocardial infarction. Male Wistar rats were pretreated for 14 days with AE or EE at doses of 75 and 150 mg/kg/day or propranolol (10 mg/kg/day). On days 15 and 16, they were injected subcutaneously with isoproterenol (85 mg/kg/day). Blood pressure and heart rate were weekly recorded by tail-cuff plethysmography during pretreatment and 24 hours after the second dose of isoproterenol. At the end of the treatment period, serum Lactate Dehydrogenase (LDH), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), cardiac nitric oxide (NO), myeloperoxidase (MPO), and oxidative stress parameters (SOD, catalase, MDA, and GSH) were assayed. Sections of left ventricle tissue were subjected to histological analysis. The vasorelaxant effects of cumulative concentrations of AE or EE (3–300 µg/mL) were evaluated on intact or endothelium-denuded isolated aorta rings precontracted with noradrenaline (1 µM). The vasorelaxant effects of the plant extracts were also tested in the presence of Nω-nitro-L-arginine methyl ester (L-NAME; 100 µM). AE and EE significantly prevented blood pressure decrease and heart rate increase elicited by isoproterenol. Both plant extracts inhibited the increase in ALT, AST, NO, and MPO but did not prevent LDH surge. Oxidative stress parameters were improved following A. pruinosum pretreatment. AE and EE highly reduced cardiomyocyte necrosis and fibrosis but did not prevent leukocyte infiltration. Both extracts induced a concentration-dependent vasorelaxation that was significantly inhibited by the destruction of the endothelium and by L-NAME. Extracts of A. pruinosum exhibited cardioprotective effects, and EE was the most active. The cardioprotective effects of A. pruinosum extracts could be ascribed to their antioxidant, antinecrotic, and endothelium-dependent vasorelaxant effects.

Amelioration of Acute Myocardial Infarction by Tribulus terrestris (Gokhru) Extract on Isoproterenol-Induced Myocardial Infarction Rats

Amelioration of Acute Myocardial Infarction by Tribulus terrestris (Gokhru) Extract on Isoproterenol-Induced Myocardial Infarction Rats

Antithrombotic Activity of the Antiplatelet Agent Angipur on the Model of Arterial Thrombosis in Rats with Isoproterenol-Induced Myocardial Infarction.

We studied the effect of Angipur on the process of experimental thrombosis induced by damage to the carotid artery wall by surface application of 50% ferric chloride (III) solution in rats without comorbidities and with isoproterenol-induced myocardial infarction. In animals without comorbidities, Angipur administered intravenously was 1.2 times less effective, in terms of ED50, than the well-known inhibitor of GPIIb/IIIa platelet receptors tirofiban. However, under conditions of non-coronary myocardial infarction, Angipur significantly prolonged the time of thrombus formation and exhibited 1.4-fold higher activity than the reference drug tirofiban.

Capillarisin Exerts Cardioprotective Effect via Modulating the Matrix Remodelling in an Experimental Model of Myocardial Infarction

Capillarisin is a primary bioactive compound derived from Artemisia capillaris is known to possess antioxidative and anti-inflammatory responses. Although, studies on the protecting effect of capillarisin against heart attack are still not clear. Therefore, in the current investigation, the experimental model of myocardial infarction was induced using isoproterenol in rats. Male Wistar rats were separated into 4 clusters as control, isoproterenol-induced myocardial infarction, capillarisin pretreated (10 mg/kg/d) before isoproterenol induction, capillarisin drug control for 4 w. Finally, infarct size, cardiac markers, such as creatinine kinase, lactate dehydrogenase, matrix proteins and microRNA signatures were revealed by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Rats induced with myocardial infarction demonstrated the abnormality in echocardiographic measurements with increased biomarkers, for example, heart type fatty acid binding protein, creatinine kinase and troponin-I compared to control. While capillarisin pre-treated rats banned myocardial infarction considerably (p<0.001) with restored cardiac functions. Besides, capillarisin pre-treatment repealed the fibrosis onset with restored matrix proteins. In addition, cardiac biomarkers, for example, atrial natriuretic peptide, erythroid transcription factor, nuclear factor of activated T cells were found increased with reduced sarco(endo)plasmic reticulum calcium-ATPase 2 in rats suffering from myocardial infarction. Additionally, the messenger ribonucleic acid of matrix signaling pathways were also found reduced obviously in capillarisin treatment which was disturbed in myocardial infarction induced rats. Capillarisin protected the hearts from failing induced by isoproterenol in rats and provides cardioprotective effect, through restoring the matrix signaling, antiinflammatory, antioxidant effect suggested possible drug candidate for the therapy of heart attack.

Ethyl pyruvate attenuates isoproterenol-induced myocardial infarction in rats: Insight to TNF-α-mediated apoptotic and necroptotic signaling interplay

The current study investigated the prophylactic effect of ethyl pyruvate (EP) in Isoproterenol (ISO) - induced myocardial infarction (MI). Ethyl pyruvate (EP) was given at a dose of 100 mg/kg i.p for 7 days, while isoproterenol (ISO) was administered at a dose of 10 mg/kg s.c. on the 6th and 7th days to induce MI. All parameters were assessed 24 and 48 h following treatment. Interestingly, EP pre-treatment significantly improved ISO-induced hemodynamic alterations and remarkably ameliorated serum levels of cardiac injury markers, Cardiac Troponin I (cTnI) and Cardiac Creatine Kinase (CK-MB). Also, EP notably suppressed levels of oxidative stress markers, total antioxidants (TAO) and malondialdehyde (MDA) as compared to ISO-treated group. Cardioprotective effects of EP were confirmed by histopathological examination. Moreover, EP remarkably attenuated ISO-induced elevation in Tumor Necrosis Factor Alpha (TNF-α) and Nuclear factor kappa-B p65 (NF-κB) expression, along with Interleukin-6 (IL-6), Monocyte chemoattractant protein 1 (MCP-1) and Inducible nitric oxide synthase (i-NOS) levels. Also, EP significantly diminished expression of apoptotic markers; caspase 8, cleaved caspase 3 and apoptotic regulator; cellular FLICE-like inhibitory protein (cFLIP). Finally, EP notably mitigated necroptotic mediators, phosphorylated receptor-interacting serine/threonine protein kinase 1 and 3 (p-RIPK1 and p-RIPK3), phosphorylated mixed lineage kinase domain-like protein (p-MLKL) and heat shock protein 70 (HSP 70) expression as compared to the ISO-treated group. Our study was the first to investigate the effect of EP on the necroptotic signaling. Taken together, EP conferred its cardioprotective effect against ISO-induced MI partially through mitigation of TNF-α and its downstream inflammatory, apoptotic and necroptotic signaling pathways.

Cardioprotective effect of hydroalcoholic extract of Brazilian red propolis against isoproterenol-induced myocardial infarction in rats

BackgroundThe pharmacological effects of propolis have mainly been investigated in various fields of medicine as an essential resource for the prevention and treatment of diseases. PurposeThis study examined the cardioprotective effect of hydroalcoholic extract of Brazilian red propolis (BRPHE) against isoproterenol (ISO)-induced myocardial infarction in rats. MethodsRats were pretreated with BRPHE (50, 75, and 150 mg/kg) for 30 days, with concurrent administration of ISO (85 mg/kg) during the last two days. The hemodynamic, biochemical, histological, and morphometric changes were monitored from control and experimental groups at the end of the experiment, i.e., on the 31st day. Phytochemical compounds were determinated by the UV–Vis spectrophotometric and UPLC-DAD-UV–Vis methods. ResultsISO-induced myocardial infarcted rats showed an increase in cardiac marker enzymes, i.e., in creatine kinase-NAC (CK-NAC) and CK-MB, tachycardia, myocardium necrosis, edema, hemorrhagic areas, infiltration of inflammatory cells like lymphocytes, and increased myocardial infarct size. However, pretreatment of ischemic rats with BRPHE significantly inhibited these effects of ISO. Thus, histopathological findings obtained for the myocardium further confirmed the biochemical findings. Flavonoids and phenols were identified in BRPHE. ConclusionOur results suggested that BRPHE pretreatment ameliorated myocardial injury in ISO-induced myocardial infarcted rats and exhibited cardioprotective activity.

Cardioprotective effects of Gynura procumbens extract on oxidative status and myocardial injury in rats with isoproterenol-induced myocardial infarction

Gynura procumbens (GP) grows abundantly in Southeast Asia. The present work was conducted to investigate the cardioprotective potential of ethanol extract of GP on cardiac markers, antioxidant levels, and histopathology of isoproterenol-induced myocardial infarction (MI). A total of 36 adult Sprague Dawley rats were randomly divided into six groups. Treatments were given via oral gavage for 28 days: two groups were given normal saline 0.9%; two groups were given GP250 mg/kg/day; and two groups were given GP500 mg/kg/day. On day 27 and 28, MI was induced with a subcutaneous injection of 85 mg/kg isoproterenol. The rats were sacrificed 48 h after the 1st injection. Cardiac markers, lipid peroxidation, oxidative status, and histopathological analyses were evaluated. Isoproterenol significantly increased the levels of troponin T, creatine kinase MB isoenzyme (CKMB), lactate dehydrogenase (LDH), and malondialdehyde (MDA), whereas the level of superoxide dismutase (SOD), catalase, and glutathione peroxidase were significantly decreased. In addition, the histopathological findings showed a necrosis of the myocardium as evidenced by neutrophil infiltration, and interstitial oedema with acceleration of apoptosis in MI. Interestingly, treatment with GP restored the levels of troponin T, LDH, MDA, SOD, and catalase significantly. Moreover, GP preserved the myocardial architecture while decreasing both necrosis and apoptosis. GP has the potential to limit myocardial injury after MI, and this is most likely achieved through its modulation of antioxidant enzyme activities.