Isoproterenol-induced Myocardial Infarction Research Articles

Protective Role of Anthraquinone Purpurin Against Cardiotoxicity Induced by Isoproterenol in Adult Wistar Rats

Background Purpurin are naturally occurring anthraquinones derived from the roots of Rubia species. Purpurin is a red-colored bioactive compound commonly used as a food colorant. In ancient times, Rubia species plants were used in Chinese medicine to treat rheumatoid arthritis. Research studies have proven purpurin exerts antimicrobial, neuromodulatory, antigenotoxic, anti-inflammatory, anticancer, and antioxidant effects. The present investigation was proposed to evaluate the efficacy of purpurin against myocardial infarction in rats. Materials and Methods Purpurin was pretreated in healthy adult male rats and subjected to a myocardial infarction with isoproterenol to assess the cardioprotective effect of purpurin. CRP, total protein, and uric acid levels were quantified to analyze the efficacy against myocardial infarction. Cardiac functional markers and antioxidant levels were measured to evaluate the role of purpurin on isoproterenol-induced myocardial infarction. Further to prove the cardioprotective efficacy of purpurin cardiac tissue ATPases and electrolytes were assessed in the experimental animals. The anti-inflammatory property of purpurin was analyzed by quantifying proinflammatory cytokines. Histopathological analysis of cardiac tissue was to confirm the protective effect of purpurin against isoproterenol-induced myocardial infarction. Results The present investigation demonstrated the significant protective effect of purpurin by decreasing the levels of CRP, uric acid levels, and total protein levels in myocardial infarction-induced rats. It restored the cardiac functional markers and glutathione system in the cardiac tissue of myocardial infarction-induced rats. It increased the levels of cardiac ATPases and reinstated the electrolytes in the cardiac tissue of myocardial infarction-induced rats. Purpurin significantly demonstrated an anti-inflammatory and cardioprotective effect that was evidenced with histopathological analysis. Conclusion Our findings prove purpurin suppresses the proinflammatory response of isoproterenol treatment and exerts a cardioprotective effect in myocardial infarction-induced rats.

The effect of eight-week resistance training on oxidative stress in isoproterenol-induced myocardial infarction in rats

IntroductionAlthough reliable new evidence has identified several advantages of resistance training (ResEx) on cardiac performance, the role of this type of training in protecting the myocardium against ischemia-reperfusion (IR) injury is not clear. The aim of this study was to investigate the effect of resistance training on cardioprotection versus IR-induced injury.Material and methods60-day-old male Wistar rats (n = 24), weighing 220–240 g, were divided into four groups: Resistance Training (ResEx), Isoproterenol (ISO), Resistance Training + Isoproterenol (ResEx + ISO), and control groups (n = 6 for each). Trained rats performed exercise in a squat-training apparatus (8–12 repetitions/set, eight sets/day, and 5 days/week for 8 weeks). After the last training session, all the rats were sacrificed with ketamine xylazine injection. The heart of rats was removed from the body and washed quickly with cold PBS, immediately put in liquid nitrogen, and stored at –70°C. Superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) activity was measured.ResultsInduction of ischemia decreased SOD and CAT activity but had no effect on the activity of GPX. Eight weeks of resistance training significantly increased activity of SOD and CAT compared to the ISO group.ConclusionsThe results of the present research demonstrated that ischemia induced by isoproterenol injection during 8 weeks of resistance training did not lead to a decrease in SOD activity and prevented the reduction of CAT activity.

PharmacologyProtective Effects of Oxyresveratrol in IsoproterenolInduced Myocardial Infarction in Rats: A Stereological Study

PharmacologyProtective Effects of Oxyresveratrol in IsoproterenolInduced Myocardial Infarction in Rats: A Stereological Study

RETRACTION: Preventive Effect of Naringin on Cardiac Mitochondrial Enzymes During Isoproterenol-induced Myocardial Infarction in Rats: A Transmission Electron Microscopic Study.

M. Rajadurai and P. Stanely Mainzen Prince, "Preventive Effect of Naringin on Cardiac Mitochondrial Enzymes During Isoproterenol-induced Myocardial Infarction in Rats: A Transmission Electron Microscopic Study," by Journal of Biochemical and Molecular Toxicology 21, no. 6 (2007): 354-361, https://doi.org/10.1002/jbt.20203. The above article, published online on 9 November 2007 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Hari K. Bhat; and Wiley Periodicals, LLC. The retraction has been agreed due to duplication of panels presented in figure 3b and 3 f. The authors did not provide an explanation or their raw data. The editors consider the results and conclusion reported in this article unreliable.

Green Synthesis and Chemical Characterization of Silver Nanoparticles by Tribulus terrestris for the Treatment of Myocardial Infarction.

Silver nanoparticles (AgNPs) are commonly utilized in the medical sector, particularly in cardiovascular applications. Nevertheless, there is a studies scarcity examining the impact of AgNPs on myocardial infarction protection. A green formulation of AgNPs was documented in the research. Different spectroscopic methods were utilized to examine the AgNPs, and their potential for treating myocardial infarction was explored. The NPs exhibited a spherical morphology upon formation. Isoproterenol (85mg/kg) was administered to induce myocardial infarction in mice. The mice were categorized into four distinct groups (n = 15): (1) untreated; (2) normal; (3,4) AgNPs + isoproterenol at various doses (5 and 50µg/kg). The activation of PPAR-Υ/NF-κB and subsequent cytokine release induced by lipopolysaccharide were quantified using real-time PCR and western blot techniques. Subsequent to the administration of AgNPs at different doses, the evaluation of cardiac function was conducted through biochemical, histochemical, and electrocardiogram (ECG) analysis. AgNPs significantly inhibit the levels of myocardial injury markers, reduce the incidence of mortality, and improve the condition of ventricular wall infarction. In addition, the administration of AgNPs effectively prevents the characteristic ST segment depression when compared to animals with myocardial infarction. The positive effects of AgNPs could potentially be attributed to the restoration of normal gene expression in PPAR-Υ/NF-κB/ΙκB-α/ΙΚΚα/β and PPAR-Υ phosphorylation pathways. Additionally, the application of AgNPs led to a reduction in the levels of pro-inflammatory cytokines in the hearts of mice suffering from myocardial infarction. The expression suppression of inflammation cytokines and cell death was significantly reduced by AgNPs. Recent findings suggest that AgNPs possess cardioprotective properties on isoproterenol-induced myocardial infarction, possibly by the inhibition of NF-κB signaling and activation of PPAR-γ. To summarize, the present study introduces a contemporary therapeutic approach for treating myocardial infarction in clinical settings.

Cardioprotective effect of CB1 receptor antagonist AM251 against β receptor-stimulated myocardial infarction via modulation of NF-kB signaling pathway in diabetic mice

We substantiated the effect of AM251, a cannabinoid receptor-1 (CB1R) antagonist, against β-receptor stimulated myocardial infarction (MI) in streptozotocin (STZ)-induced diabetic mice via modulation- of the NF-kB signaling pathway. The different parameters were assessed such as ECG, hemodynamic, cardiac injury markers, oxidative stress parameters, pro-inflammatory cytokines, and histopathological abnormalities. Mice were fed a high-fat diet for 30 days. On day 7, to trigger diabetes, 150 mg/kg of STZ was injected intraperitoneally. On day 10, to determine whether diabetes developed, the blood level of glucose was monitored. From days 11–30, diabetic mice were injected with either CB1R agonist oleamide or antagonist AM251 or both, with concurrent administrations of β-agonist isoproterenol on days 28 and 29 to induce MI. In comparison to normal, the myocardial infarcted diabetic animals demonstrated alterations in ECG, hemodynamic profiles, and diminished enzymatic activities (CK-MB, LDH, SOD, GSH, catalase), with concurrently increased MDA levels, which indicated increased oxidative stress in the myocardium. Additionally, higher concentrations of cytokines that signal myocardial inflammation, such as IL-1β, IL-6, and TNF-α, were also noted. Furthermore, elevated myonecrosis, edema, and cell infiltration which is confirmed by histopathology of heart tissue. Treatment with AM251 significantly ameliorated myocardial redox status, reduced cytokines, and repaired enzymatic activities leading to subsequent recovery in cardiac function. AM251 effectively suppressed myonecrosis and edema. This study also showed that AM251 protects against myocardial inflammation and oxidative stress triggered by isoproterenol by blocking NF-kB signalling pathway. However, upregulation of the CB1R through oleamide showed significant cardiac toxicity. Conversely, the concurrent administration of oleamide and AM251 failed to induce cardiotoxic effects in isoproterenol-induced MI in diabetic mice which indicates downregulation of the CB1R might be associated with the cardioprotective effect.

Cardioprotective role of long-term kefir and omega-3 fatty acid supplementation on myocardial apoptosis via oxidative stress-mediated lysosomal cathepsin release in isoproterenol-induced myocardial infarction rat model

Objective: The antiapoptotic and antioxidative role of long-term kefir and omega-3 fatty acids and their relationship with cysteine proteases on isoproterenol (ISO) induced myocardial infarction (MI) experimental model was investigated in our study. Material and Methods: Fifty male Sprague-Dawley rats were evenly divided into five distinct groups (n=10): Control, MI, kefir +MI, omega-3+MI, and kefir+omega 3+MI groups. Kefir 10% (with drinking water) and omega-3 fatty acid (30 mg/day per 100g body weight into the standard chow) were administrated during 30 days. ISO was subcutaneously injected into the rats (100 mg/ kg b.w.) on the 29th and 30th days. Myocardial tissue and blood samples were taken 12 hours after the last ISO dose. Creatine kinase MB (CK-MB) activities were measured in serum samples. Caspase-3, superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), DNA fragmentation, cathepsin B and L levels, were measured in myocardial tissue. Results: Serum CK-MB (p<0.05) and cardiac tissue MDA (p>0.05), NO (p<0.01), caspase 3 (p<0.01), DNA fragmentation (p<0.001), cathepsin B (p<0.05) and L (p<0.05) activities were increased and SOD (p<0.001) activities were decreased in MI group compared to control group. The preventive effects of long-term therapy with kefir and omega-3 fatty acids have been demonstrated on apoptosis, oxidative stress markers, and cysteine protease enzymes. Conclusion: Our results showed that long-term administration of kefir and omega-3 fatty acids might be effective in reducing myocardial apoptosis through oxidative stress-mediated release of cysteine proteases in myocardial infarction, especially in the kefir and combined therapy groups.

Cardioprotective effects of nanoparticles green formulated by Spinacia oleracea extract on isoproterenol-induced myocardial infarction in mice by the determination of PPAR-γ/NF-κB pathway

Abstract We developed a contemporary cardioprotective medication using silver nanoparticles (AgNPs) loaded with Spinacia oleracea to treat isoproterenol (ISO)-induced myocardial infarction in mice, focusing on the PPAR-γ/NF-κB pathway. The physicochemical techniques, such as Fourier-transform infrared spectroscopy, field emission scanning electron microscopy, ultraviolet–visible spectroscopy, and energy dispersive X-ray analysis, were employed to characterize the AgNPs. In the in vivo experiment, myocardial infarction was induced in mice by administering ISO subcutaneously at a dose of 40 mg/kg every 12 h for a total of three times. The mice were divided into five groups in a random manner: (1 and 2) ISO + AgNPs at varying doses (10 and 20 μg/mL) and time points; (3) ISO; and (4) control. Following the treatment, cardiac function was assessed through electrocardiogram, as well as biochemical and histochemical analyses. In the study, we examined the inflammatory reactions and cell death in human coronary artery endothelial cells exposed to lipopolysaccharide (LPS). The PPAR-γ/NF-κB activation by LPS and the resulting cytokine production were checked using real-time PCR and western blot techniques. The typical ST segment depression in myocardial infarction mice is significantly inhibited by the administration of AgNPs. Additionally, the treatment with AgNPs leads to a significant improvement in ventricular wall infarction, a decrease in mortality rate, and inhibition of myocardial injury marker levels. Furthermore, the application of AgNPs resulted in a decrease in the inflammatory environment within the hearts of mice with myocardial infarction. This effectively prevented the increase in TNF-α, IL-1β, and IL-6. The gene expression normalization of PPAR-γ/NF-κB/IκB-α/IKKα/β and PPAR-γ phosphorylation could potentially be linked to the advantageous impacts of AgNPs. In the context of an in vitro experiment, the administration of AgNPs demonstrated a notable decrease in cell death and inflammation cytokines expression inhibition. The myocardial infarction mice in the pre + post-ISO group appear to experience more noticeable cardioprotective effects from the treatment with AgNPs than those in the post-ISO group. Our research findings demonstrate that AgNPs possess cardioprotective efficacies in ISO-induced myocardial infarction. This beneficial effect may be attributed to the PPAR-γ activation and the NF-κB signaling inhibition. Consequently, our study presents a novel remedial approach for myocardial infarction treatment in clinical settings.

Development of optimized resveratrol/piperine-loaded phytosomal nanocomplex for isoproterenol-induced myocardial infarction treatment

Cardiovascular disease is a significant and ever-growing concern, causing high morbidity and mortality worldwide. Conventional therapy is often very precarious and requires long-term usage. Several phytochemicals, including Resveratrol (RSV) and Piperine (PIP), possess significant cardioprotection and may be restrained in clinical settings due to inadequate pharmacokinetic properties. Therefore, this study strives to develop an optimized RSV phytosomes (RSVP) and RSV phytosomes co-loaded with PIP (RPP) via solvent evaporation method using Box-Behnken design to enhance the pharmacokinetic properties in isoproterenol-induced myocardial infarction (MI). The optimized particle size (20.976 ± 0.39 and 176.53 ± 0.88 nm), zeta potential (−33.33 ± 1.5 and −48.7 ± 1.6 mV), drug content (84.57 ± 0.9 and 87.16 ± 0.6%), and %EE (70.56 ± 0.7 and 67.60 ± 0.57%) of the prepared RSVP and RPP, respectively demonstrated enhanced solubility and control release in diffusion media. The oral administration of optimized RSVP and RPP in myocardial infarction-induced rats exhibited significant (p < 0.001) improvement in heart rate, ECG, biomarker, anti-oxidant levels, and no inflammation than pure RSV. The pharmacokinetic assessment on healthy Wistar rats exhibited prolonged circulation (>24 h) of RSVP and RPP compared to free drug/s. The enhanced ability of RSVP and RPP to penetrate bio-membranes and enter the systemic circulation renders them a more promising strategy for mitigating MI.

Investigating the Cardio-protective Activity of Agaricus bisporus in Wistar Rats Induced with Myocardial Infarction

Myocardial infarction is now recognized as one of the chronic diseases and the leading cause of death across the globe. The use of plants abundant in our environment, especially Agaricus bisporusprovides a cheap alternative to combat this common foe of mankind. Hence, this study was carried out to evaluate the cardio-protective effect of the leaf extract of Agaricus bisporus in isoproterenol-induced myocardial infarction. Fresh sample of Agaricus bisporus were purchased from a market at Asaba, Delta State, Nigeria. The samples were thereafter shredded with a knife and oven-dried at 40oC and pulverized and extracted, using Solvent-solvent (ethanol and water) (7:3) via maceration for 72 hr. The filtrate was evaporated to dryness to obtain the ethanol extract which was used for further bioassay study. The animals were administered with the extract of A. bisporus orally for fourteen consecutive days at a divided dose of 100 mg/kg, 200 mg/kg and 400 mg/kg body weights and thereafter 0.2 ml isoproterenol (ISO) at 150 mg/kg was injected intraperitoneally at an interval of 24 h on the 15th and 16th day. Subsequently, the blood pressures were monitored and blood collected for bioassay studies. Assay of High density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), triglyceride (TG) and total cholesterol (TC) levels as well as activities of lactate dehydrogenase (LDH), were carried out with standard assay kit sourced from Randox laboratories Ltd, United Kingdom with maximum adherence to the manufacturer’s instruction. Results showed a significant increase (P&lt;0.05) in high density lipoproteins (HDL) levels and lactate dehydrogenase (LDH) activities with a significant decrease (P&gt;0.05) in low density lipoproteins (LDL) and triglyceride levels in a dose-dependent manner (100&lt;200&lt;400 mg/kg body weight) among the extract treated groups when compared to the untreated control group. Conversely, total cholesterol levels of extract treated groups showed no significant difference when compared with the untreated control group.The findings of this work have shown that extract of Agaricus bisporus could help to mitigate cardiovascular diseases and could be used to produce plant based products to combat myocardial infarction, thereby improving general wellbeing.

Investigating the Cardio-protective Activity of Volvariella volvacea in Isoproterenol-induced Myocardial Infarction Using Animal Model: An In vivo Approach

Ischemic heart disease (IHD) is a severe cardiovascular condition characterized by impaired blood flow to the heart muscle, leading to tissue damage and dysfunction. Among different natural resource, mushrooms are now becoming more attractive because of its strong nutritional value and therapeutic potentiality. Wild edible fleshy fungi like Volvariella volvacea have been instrumental in preventing and treating chrome diseases. Hence, this study was carried out to evaluate the cardio-protective activity of Volvariella volvacea in isoproterenol-induced myocardial infarction using animal model. Twenty five (25) male wistar rats were randomly grouped into five classes (A, B, C, D and E) of five rats each. Groups A, B and C were pre-treated with 100mg/kg, 200mg/kg and 400mg/kg of Volvariella volvacea extract respectively. Group D was administered 10 mg of lisinopril (standard drug), this served as the positive control group while group E was administered 0.2 ml distilled water, and this served as the negative control group. All the rats were intraperitoneally induced with 150 mg of isoproterenol after fourteen days (two weeks) of pretreatment. Cardiac biomarker (lactate dehydrogenase (LDH)), was measured to assess cardiac injury, using standard method while lipid bioassay such as high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG) and total cholesterol (TC) were assayed using standard assay kits. Results showed that rats pre-treated with Volvariella volvacea extract showed significant effect on cardiac biomarkers compared to the control group. Results showed a significant increase (P&lt;0.05) in high density lipoproteins (HDL) levels and lactate dehydrogenase (LDH) activities with a significant decrease (P&gt;0.05) in low density lipoproteins (LDL) and triglyceride levels in a dose-dependent manner (100&lt;200&lt;400 mg/kg body weight) among the extract treated groups when compared to the untreated control group. However, total cholesterol levels of extract treated groups showed no significant difference when compared with the untreated control group. This study has shown that extract of Volvariella volvacea could help to mitigate cardiovascular diseases and could be used to produce plant based products to combat Ischemic heart disease, and consequently improving general wellbeing.

Evaluation of the cardioprotective activity of summer savory (Satureja hortensis L.) extract in experimental rats with Isoproterenol-induced myocardial infarction

BackgroundMyocardial infarction (MI) is a serious heart ailment that requires cutting-edge remedies for effective treatment. This study examines the possible cardioprotective effects of a hydroalcoholic extract from Satureja hortensis L. (HASH) in rats with isoproterenol (ISO) induced myocardial infarction. MethodsThe rats were pretreated orally with hydroalcoholic extract of Satureja hortensis low (200 mg/kg), high dose (400 mg/kg), and metoprolol (10 mg/kg), in their respective groups for 30 days, followed by two subcutaneous doses of isoproterenol (ISO). Blood was obtained to measure biochemicals such as creatine kinase-MB (CK-MB), Troponin I, Alanine transaminase (ALT), Aspartate transaminase (AST), and lactate dehydrogenase (LDH), and an electrocardiogram (ECG) of a rat was recorded after the experiment. Myocardial integrity was examined histopathologically, and malondialdehyde (MDA) levels and antioxidant enzyme concentrations were assessed using heart tissue homogenate. ResultsRats with myocardial infarction caused by ISO displayed significantly (P < 0.001) augmented CK-MB, Troponin I, LDH, AST, and ALT levels with aberrant ECG patterns, and alteration in cardiac mass as well as enhaced oxidative stress marker levels. Besides, biochemical results were validated by myocardium histology. Pre-treatment of animals with a high dose (400 mg/kg) of HASH or standard cardioprotective agent (metoprolol) prevented the ISO-induced alterations in the above parameters to a significant (P < 0.01) level as well as metabolic derangements and functional alterations. ConclusionsOur research suggests that HASH pre-treatment has cardioprotective action and can prevent myocardial toxicity caused by ISO. Therefore, Satureja hortensis L. extract might be a promising therapeutic plant that can be further investigated for potential cardioprotective properties.

Protective Effect of Prunetin on Isoproterenol-Induced Myocardial Infarction in Wistar Rats via Biochemical Characterization.

The development of MI following ischemia damage is influenced by oxidative stress. Myocardial Infarction (MI) generates myocardial ischemia injury, which damages the cardiomyocytes. Ischemia builds up to a critical level over time in MI, causing permanent myocardial cell damage or death. The current study sought to determine whether Prunetin (PRU) could protect against Isoproterenol (ISO)-induced cardiac heart failure in rats by examining cardiac diagnostic markers, lipid peroxidation products, enzymatic and non-enzymatic antioxidant levels, and histological changes. PRU (20 mg/kg bwt) was orally administered for 19 days to rats, and after the treatment, ISO (85 mg/kg bwt) was subcutaneously administered with an intermission of 24 h for a couple of days to induce myocardial infarction on 20th and 21st days. ISO-treated rats exhibited considerable alterations in cardiac-sensitive markers in the serum. The levels of lipid peroxidation markers augmented drastically in the plasma and myocardium. Enzymatic antioxidant levels in erythrocytes and myocardium and the states of non-enzymatic antioxidants were diminished in the plasma and heart tissue of ISO-treated rats. The histopathological examination of heart tissue exhibited cardiac damage in ISO-induced rats. The oral administration of PRU significantly lowered the levels of lipid peroxidation and biochemical indicators, while significantly improving the antioxidant system function of ISO-interposed rats. In PRU-treated ISO-injected rats, histological examinations revealed suppressed myocardial destruction. Our research shows that oral pretreatment of PRU prevented ISO-induced oxidative stress in MI.

Protective effects of ginsenoside F2 on isoproterenol-induced myocardial infarction by activating the Nrf2/HO-1 and PI3K/Akt signaling pathways

BackgroundGinsenoside F2 (GF2) serves as the principal intestinal metabolite resulting from the oral intake of Panax ginseng and Panax quinquefolius, exhibiting antioxidative, hypolipidemic, antitumor, and anti-inflammatory properties. Nevertheless, its effect on myocardial infarction (MI) is still unknown. PurposeThe purpose of this study is to investigate the protective effect and the underlying mechanisms of GF2 against isoproterenol (ISO)-induced MI. MethodsISO-induced H9c2 cardiomyocytes and MI rat models were utilized as in vitro and in vivo models to evaluate the impact of anti-MI of GF2. The underlying mechanisms were investigated using a variety of methodologies, including electrocardiography, Western blot analysis, histopathological examination, immunofluorescence, immunohistochemistry, and ELISA techniques. ResultsIn vivo experiments, our results indicated that GF2 significantly ameliorated ISO-induced electrocardiographic (ECG) abnormalities, myocardial fiber necrosis, rupture, fibrosis of myocardial tissues, and suppressed cardiac enzyme activities. Meanwhile, GF2 notably raised the activity of antioxidant enzymes like CAT, GSH, and SOD. Furthermore, it downregulated Keap1 expression level while upregulating NQO1, Nrf2, and HO-1 expression levels. Additionally, GF2 suppressed the expression of the cleaved caspase-3 and pro-apoptotic protein Bax while promoting the expression of anti-apoptotic proteins Bcl-2, p-PI3K, and p-Akt. TUNEL fluorescence results also demonstrated that GF2 effectively inhibited cardiomyocyte apoptosis. Furthermore, consistent with the results of animal experiments, GF2 considerably attenuated ROS generation, changed apoptosis and mitochondrial function, and reduced oxidative stress in ISO-induced H9c2 cardiomyocytes through activating Nrf2/HO-1 and PI3K/Akt signaling pathways. ConclusionTaken together, GF2 ameliorated MI by preventing cardiocyte apoptosis, oxidative stress, and mitochondrial dysfunction via modulating the Nrf2/HO-1 and PI3K/Akt signaling pathways, showing potential as a treatment strategy for treating MI.

Punicalagin attenuates isoproterenol-induced myocardial infarction through nuclear factor erythroid 2-related factor 2/silent information regulator transcript-1-mediated inhibition of inflammation and cardiac stress markers in experimental animal models.

Myocardial infarction (MI) is a significant global health issue and the leading cause of death. Myocardial infarction (MI) is characterized by events such as damage to heart cells and stress generated by inflammation. Punicalagin (PCN), a naturally occurring bioactive compound found in pomegranates, exhibits a diverse array of pharmacological effects against many disorders. This study aimed to assess the preventive impact of PCN, with its potential anti-inflammatory and antioxidant properties, on myocardial injury caused by isoproterenol (ISO) in rats and elucidate the possible underlying mechanisms. Experimental rats were randomly categorized into four groups: control group (fed a regular diet for 15 days), PCN group (orally administered PCN at 50 mg/kg body weight (b.w.) for 15 days), ISO group (subcutaneously administered ISO (85 mg/kg b.w.) on days 14 and 15 to induce MI), and PCN+ISO group (orally preadministered PCN (50 mg/kg b.w.) for 15 days and administered ISO (85 mg/kg b.w.) on days 14 and 15). The rat cardiac tissue was then investigated for cardiac marker, oxidative stress marker, and inflammatory marker expression levels. PCN prevented ISO-induced myocardial injury, suppressing the levels of creatine kinase-myocardial band, C-reactive protein, homocysteine, cardiac troponin T, and cardiac troponin I in the rats. Moreover, PCN treatment reversed (P<0.01) the ISO-induced increase in blood pressure, attenuated lipid peroxidation markers, and depleted both enzymatic and nonenzymatic markers in the rats. Additionally, PCN inhibited (P<0.01) ISO-induced overexpression of oxidative stress markers (p-38, p-c-Jun N-terminal kinase, and p-extracellular signal-regulated kinase 1), inflammatory markers (nuclear factor-kappa B, tumor necrosis factor-alpha, and interleukin-6), and matrix metalloproteinases and decreased the levels (P<0.01) of apoptosis proteins in the rats. Nuclear factor erythroid 2-related factor 2/silent information regulator transcript-1 (Nrf2/Sirt1) is a major cellular defense protein that regulates and scavenges oxidative toxic substances through apoptosis. Therefore, overexpression of Nrf2/Sirt1 to inhibit inflammation and oxidative stress is considered a novel target for preventing MI. PCN also significantly enhanced the expression of Nrf2/Sirt1 in ISO-induced rats. Histopathological analyses of cardiac tissue revealed that PCN treatment exhibited a protective effect on the heart tissue, mitigating damage. These findings show that by activating the Nrf2/Sirt1 pathway, PCN regulates oxidative stress, inflammation, and apoptosis, hence providing protection against ISO-induced myocardial ischemia.

Cardioprotective potential of compound 3K, a selective PKM2 inhibitor in isoproterenol-induced acute myocardial infarction: A mechanistic study

Myocardial infarction (MI) or heart attack arises from acute or chronic prolonged ischemic conditions in the myocardium. Although several risk factors are associated with MI pathophysiology, one of the risk factors is an imbalance in the oxygen supply. The current available MI therapies are still inadequate due to the complexity of MI pathophysiology. Pyruvate kinase M2 (PKM2) has been implicated in numerous CVDs pathologies. However, the effect of specific pharmacological intervention targeting PKM2 has not been studied in MI. Therefore, in this study, we explored the effect of compound 3K, a PKM2-specific inhibitor, in isoproterenol-induced acute MI model. In this study, in order to induce MI in rats, isoproterenol (ISO) was administered at a dose of 100 mg/kg over two days at an interval of 24 h. Specific PKM2 inhibitor, compound 3K (2 and 4 mg/kg), was administered in MI rats to investigate its cardioprotective potential. After the last administration of compound 3K, ECG and hemodynamic parameters were recorded using a PV-loop system. Cardiac histology, western blotting, and plasmatic cardiac damage markers were evaluated to elucidate the underlying mechanisms. Treatment of compound 3K significantly reduced ISO-induced alterations in ECG, ventricular functions, cardiac damage, infarct size, and cardiac fibrosis. Compound 3K treatment produced significant increase in PKM1 expression and decrease in PKM2 expression. In addition, HIF-1α, caspase-3, c-Myc, and PTBP1 expression were also reduced after compound 3K treatment. This study demonstrates the cardioprotective potential of compound 3K in MI, and its mechanisms of cardioprotective action.

Gynostemma pentaphyllum Makino exerts cardioprotective effects by improving hemodynamic, biochemical and histopathological changes through activation of PI3K signalling in isoproterenol-induced myocardial infarction in rats.

To evaluate the cardioprotective effects of Gynostemma pentaphyllum Makino in isoproterenol-induced myocardial infarction in rats and to evaluate the role of phosphatidylinositol 3-kinases (PI3K) in cardioprotection. The protective effect of the hydroalcoholic leaf extract of Gynostemma pentaphyllum (LEGP) on the heart was investigated against isoproterenol (ISO)-induced MI in rats. Preliminary phytochemical screening was performed followed by molecular docking. For the in vivo studies Wistar albino rats (Male) were divided among different groups. Different parameters were evaluated such as heart weight index, Electrocardiogram (ECG) analysis, triphenyl tetrazolium chloride assay, cardiac enzyme markers, oxidative stress, antioxidant enzymes, PI3K levels, and histopathology of cardiac tissue. Results showed that LEGP improved the electrocardiogram, reduced infarct size, and decreased the levels of cardiac enzyme markers and oxidative stress, while antioxidant enzymes and PI3K levels were increased. LEGP protected the heart against ISO-induced MI in rats by improving hemodynamic, biochemical and histological attributes. These protective effects were produced by the phytoconstituents of the LEGP through modulation of the PI3K signalling pathway.

Cardioprotective Potential of Resveratrol Alone and in Combination with Piperine on Isoproterenol-induced Myocardial Infarction in Rat: Investigation on Oral Bioavailability of Resveratrol

Cardioprotective Potential of Resveratrol Alone and in Combination with Piperine on Isoproterenol-induced Myocardial Infarction in Rat: Investigation on Oral Bioavailability of Resveratrol

Diagnostic Potential of miRNA-15a-5p for the Early Detection of Myocardial Infarction

Myocardial infarction (MI), also known as a heart attack, is caused by reduced or complete cessation of blood flow to the part of the myocardium. MicroRNAs (miRNAs) are key regulators in various cellular mechanisms and have the potential to be used as diagnostic markers in certain diseases such as MI, atherosclerosis, heart failure coronary artery disease, hypertrophy, and fibrosis. The present study was conducted to assess the early diagnostic potential of circulatory miRNA-15a-5p. By using bioinformatics tools, it was found that BCL2, an antiapoptotic gene, is the putative target of miRNA-15a-5p. The blood was collected from the 50 MI patients recruited in Lady Reading Hospital Peshawar. qRT-PCR analysis showed significantly upregulated miRNA-15a-5p in MI patients’ blood and isoproterenol-induced MI rats’ blood and tissue samples. The decreased level of the antiapoptotic gene, BCL2, was confirmed by qRT-PCR in the circulation of both MI patients and MI rat model. The toxic potential of isoproterenol for MI induction in rats was confirmed by disrupted heart tissue histology, increased reactive oxygen species (ROS) and decreased antioxidative enzymes such as superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), reduced glutathione (GSH) and ascorbate peroxidase (APX) in rat serum and tissue homogenate samples. In serum samples, liver function tests, and lipid profiling showed elevated levels in the MI rat model. Concludingly, this study provides future insights for miRNA research that will advance the development of diagnostic markers for the early detection of MI in patients.

Investigation of the effect of thymoquinone on kidney damage in isoproterenol-induced myocardial infarction in rats and cardiorenal interactions

This study aimed to determine whether thymoquinone has any protective effects on renal tissue after an isoproterenol-induced myocardial infarction (MI). Experimental groups were formed as 4 groups (n=8). Control group (C). Thymoquinone group (THQ), 20 mg/kg single dose intragastric (i.g.) daily for seven days. Isoproterenol group (ISO) was administered 100 mg/kg intraperitoneally in two doses on days 7 and 8 of the experiment. Thymoquinone+Isoproterenol group (THQ+ISO), THQ 20 mg/kg i.g. was administered once a day for seven days. In addition, two doses of ISO 100 mg/kg i.p. were administered on the seventh and eighth days. Kidney tissues were evaluated histopathologically. Kidney tissues were evaluated histopathologically. Tumour necrosis factor alpha(TNF-α) and alpha Smooth Muscle Actin(α-SMA) immunoreactivity density changes were determined by immunohistochemistry. Glutathione(GST), Glutathione S-transferases(GSTs) and Interleukin-6(IL-6) levels were evaluated by ELISA method. Isoproterenol injection caused severe histopathological changes on kidney tissue. Also TNF-α and α-SMA levels were found to be higher in groups where ISO was administered. THQ could be effective on kidney tissue to partially correct these histopathological damages, by decreasing fibrosis and inflammation. This study shows that treatment with THQ is effective in preventing kidney damage caused by ISO-induced MI. We think that THQ as a supplementary food will be effective to prevent kidney damage.