ISO-induced Myocardial Infarction Research Articles

Daidzein alleviates isoproterenol-induced cardiac injury in rats via NF-kB pathway inhibition

The current study set out to explore the anti-inflammatory effects of Daidzein (Dz) on the isoproterenol (Iso)-induced myocardial infarction (MI) in male Wistar rats. Iso(80 mg/kg) was injected subcutaneously into rats to cause MI for two days at intervals of 24 hours. ELISA kits were used to measure the amounts of TNF-α & IL-6 in cardiac tissues. The quantity of NF-kB in the cytosol and nuclei was measured using a western blot approach. H&E staining was used to identify histological cardiac changes. In rats with Iso-induced myocardial infarction, Dz therapy shrunk the size of the infarct and reduced histological anomalies in the myocardium. Dz significantly lowered cardiac pro-inflammatory cytokine levels and prevented NF-kB nuclear translocation in MI-damaged rats, substantially reversing Iso-induced damage. This research shows that daidzein treatment in vivo reduces Iso-induced myocardial damage by preventing NF-kB activation, which may therefore reduce the release of inflammatory cytokines.

Targeting the PANoptosis signaling pathway for myocardial protection: therapeutic potential of Xian Ling Gu Bao capsule.

Introduction: Myocardial infarction (MI), the most prevalent ischemic heart disease, constitutes a primary cause of global cardiovascular disease with incidence and mortality. The pathogenesis of MI is exceedingly intricate, with PANoptosis playing a pivotal role in its pathological process. Xian Ling Gu Bao capsule (XLGB) contains various active components, including flavonoids, terpenes, and phenylpropanoids, and exhibits a wide range of pharmacological activities. However, it remains unclear whether XLGB can protect the myocardium from damage after MI. This study aimed to investigate the impact of XLGB on isoprenaline (ISO)-induced MI in mice and its potential mechanisms. Methods: This study assessed the protective effects of XLGB against ISO-induced MI through techniques such as echocardiography, HE staining, Masson staining, and enzyme-linked immunosorbent assay (ELISA). Furthermore, the potential mechanisms of XLGB's protective effects on MI were explored using bioinformatics, molecular docking, and molecular dynamics simulations. These mechanisms were further validated through immunofluorescence staining and Western blotting. Results: The results demonstrated that various doses of XLGB exhibited a significant reduction in myocardial injury induced by myocardial infarction. Intriguingly, higher dosages of XLGB displayed superior therapeutic efficacy compared to the positive control metoprolol. This protective effect is primarily achieved through the inhibition of oxidative stress and the inflammatory processes. Furthermore, we have elucidated that XLGB protected the myocardium from MI-induced damage by suppressing PANoptosis, with a critical role played by the NLRP3/Caspase3/RIP1 signaling pathway. Of particular note, the primary compounds of XLGB were found to directly interact with NLRP3/Caspase3/RIP1, a discovery further validated through molecular docking and molecular dynamics simulations. This suggests that NLRP3/Caspase3/RIP1 may be a therapeutic target for XLGB-induced myocardial protection. Conclusion: In summary, our findings reveal a novel property of XLGB: reverses myocardial damage following MI by inhibiting the NLRP3/Caspase3/RIP1-mediated PANoptosis pathway.

BAO-Ag-NPs as Promising Suppressor of ET-1/ICAM-1/VCAM-1 Signaling Pathway in ISO-induced AMI in Rats.

Acute myocardial infarction (AMI) is the most prevalent cause of myocardial fibrosis and the leading cause of mortality from cardiovascular disease. The goal of this work was to synthesize Balanites aegyptiaca oil-silver nanoparticles (BAO-Ag-NPs) and evaluate their cardioprotective effect against ISO-induced myocardial infarction in rats, as well as their mechanism. BAO was isolated, and the unsaturated fatty acids were estimated. BAO-Ag-NPs was prepared, LD50 was calculated to evaluate its cardioprotective activity against ISO (85 mg/kg)- induced AMI. Different doses of BAO-Ag-NPs (1/50 LD50; 46.6 mg/kg.b.w and 1/20 LD50; 116.5 mg) were received to the rats. The total fatty acids and unsaturated fatty acids generated by BAO were 909.63 and 653.47 mg/100 g oil, respectively. Oleic acid methyl ester, 9-Octadecenoic acid methyl ester, and 9, 12-Octadecadienoic acid methyl ester were the predominant ingredients, with concentrations of 107.6, 243.42, and 256.77 mg/100 g oil, respectively. According to TEM and DLS examinations, BAO-Ag-NPs have a size of 38.20±2.5 nm and a negative zeta potential of -19.82 ± 0.30 mV, respectively. The LD50 of synthesized BAO-Ag-NPs is 2330 mg. On the other hand, BAO-Ag-NPs reduce myocardial necrosis by lowering increased BNP, cTnI, CK-MB, TC, TG, MDA, MMP2, TGF-β1, PGE2, and IL-6 levels. Furthermore, BAO-Ag-NPs inhibit the expression of ET-1, ICAM-1, and VCAM-1 genes. BAO-Ag-NPs given to ISO-treated rats enhance HDL-C, CAT, and GSH levels when compared to the ISO-treated group of rats. Histopathological findings suggested that BAO-Ag-NPs enhance cardiac function by increasing posterior wall thickness in heart tissues. BAO-Ag-NPs protect against AMI in vivo by regulating inflammation, excessive autophagy, and oxidative stress, as well as lowering apoptosis via suppression of the ET-1, ICAM-1, and VCAM-1 signaling pathways.

Moderate-Intensity Swimming Alleviates Oxidative Injury in Ischemic Heart

The global burden of cardiovascular diseases is indisputable, as it claims nearly 18 million lives a year. In this current study, we aimed to prove that exercise, a cornerstone in cardiovascular disease management, emerges as a powerful tool in the pathology of myocardial ischemia. Male rats were divided into three groups: pre-swimming training + isoproterenol (ISO) treated, isoproterenol-treated, and control-sedentary. Myocardial infarction was induced by the subcutaneous injection of 1.0 mg/kg ISO. After the subsequent rest period, the animals swam for 3 weeks, every day for 25 min. At the end of the experiment, the serum levels of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), as well as the cardiac concentrations of reactive oxygen species (ROS), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were determined. Our results indicate that both cardiac injury biomarkers (ANP, BNP) and ROS levels were significantly lower in swimming rats compared to the sedentary animals. Moreover, the level of enzymatic components of the intracellular antioxidant system, CAT, SOD, and GPx were increased in swimming animals after ISO-induced myocardial infarction. Our findings support the fact that moderate-intensity swimming training can be efficiently used to prevent myocardial infarction-induced ischemic injury, by inhibiting ROS production and strengthening intracellular antioxidant defense.

Cardioprotective Potential of <i>Albizzia lebbeck</i>: Insights Isoproterenol-Induced Myocardial Infarction in Rats

This study investigates the cardioprotective potential of Albizzia lebbeck (Shirish) ethanol leaf extract against Isoproterenol (ISO)-induced myocardial infarction in Wistar albino rats. Cardiovascular Diseases (CVDs) are a major global health concern, contributing significantly to morbidity and mortality. A. lebbeck, a medicinal plant with documented pharmacological activities, has not been scientifically studied for its cardioprotective properties. The research utilised a rat model of ISO-induced myocardial infarction, a well-established experimental approach to study preventive effects on myocardial damage. The study included the isolation and preparation of A. lebbeck ethanol leaf extract (MEAL) and its administration at different doses (200 mg/kg and 400 mg/kg) to ISO-treated rats. Various parameters, including relative organ weight, cardiac biomarkers (cTnI, LDH, CK-MB), total proteins, oxidative stress markers (SOD, MDA), and histopathological changes, were assessed. The results revealed that ISO administration induced cardiac hypertrophy, increased serum biomarkers, and oxidative stress, indicating myocardial damage. Treatment with MEAL, especially at the higher dose (400 mg/kg), significantly mitigated these effects. MEAL administration reduced the heart-to-body weight ratio, normalised serum biomarkers, restored endogenous antioxidant enzyme levels, and showed a protective effect against structural damage in histopathological examination. In conclusion, A. lebbeck ethanol leaf extract demonstrated significant cardioprotective effects against ISO-induced myocardial infarction in rats. These findings suggest the potential of A. lebbeck as a natural therapeutic agent for preventing or ameliorating cardiac damage associated with stress-induced conditions. Further research is warranted to elucidate the specific mechanisms underlying its cardioprotective properties and explore its potential clinical applications.

Protective Role of Pistacia Palaestina Boiss Fruit and Leaf Extracts in Isoproterenol-Induced Cardiac Ischemia

Myocardial infarction (MI) is one of the leading causes of death worldwide. In this study aimed to investigate the protective effects of Pistacia palaestina Boiss (PP) leaf and fruit extracts, which are thought to have antioxidant and anti-inflammatory properties, in isoproterenol (ISO)-induced MI. 80 Spraque-Dawley rats were divided into 10 groups. The control group was given saline. PP leaf and fruit extracts at doses of 250 mg/kg and 500 mg/kg applied by gavage for 21 days. ISO 100 mg/kg subcutaneously was administered to the MI and MI-treatment groups on the 17th and 18th days of the experiment. Thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) levels, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured in heart tissue. In serum, Troponin t, CK-MB; pro-inflammatory cytokine necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and IL-6; Anti-inflammatory IL-10 levels were determined by the ELISA method. Heart tissue was examined by haematoxylin-eosin staining. While lipid peroxidation indicator TBARS activity increased in the MI group, antioxidant enzyme activities and GSH levels decreased. While Troponin t, CK-MB, TNF-α, IL-1β and IL-6 levels increased, anti-inflammatory IL-10 levels decreased. Low and high dose PP leaf and fruit extracts significantly decreased TBARS, Troponin t, CK-MB, TNF-α, IL-1β, IL-6 levels, improved antioxidant enzyme activity, GSH and IL-10 levels. PP ameliorated cardiac biomarkers and histopathological changes in ISO-induced MI by suppressing oxidative stress and inflammation. PP extracts may play an important cardioprotective role in the treatment of MI with their antioxidant and anti-inflammatory effects.

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.

Chitosan-sodium alginate-polyethylene glycol-Ally isothiocyante nanocomposites ameliorates isoproterenol-induced myocardial infarction in rats.

Myocardial infarction (MI) is a common type of ischemic heart disease that affects millions of people worldwide. In recent times, nanotechnology has become a very promising field with immense applications. The current exploration was conducted to synthesize the chitosan-sodium alginate-polyethylene glycol-Ally isothiocyanate nanocomposites (CSP-AIso-NCs) and evaluate their beneficial roles against the isoproterenol (ISO)-induced MI in rats. The CSP-AIso-NCs were prepared and characterized by several characterization techniques. The MI was initiated in the rats by the administration of 85 mg/kg of ISO for 2 days and treated with 10 and 20 mg/kg of CSP-AIso-NCs for 1 month. The changes in heart weight and bodyweight were measured. The cardiac function markers were assessed with echocardiography. The lipid profiles, Na+, K+, and Ca2+ ions, cardiac biomarkers, antioxidant parameters, and inflammatory cytokines were assessed using corresponding assay kits. The histopathological study was done on the heart tissues. The UV spectral analysis revealed the maximum peak at 208 nm, which confirms the formation of CSP-AIso-NCs. The FT-IR analysis revealed the occurrence of different functional groups, and the crystallinity of the CSP-AIso-NCs was proved by the XRD analysis. DLS analysis indicated the size of the CSP-AIso-NCs at 146.50 nm. The CSP-AIso-NCs treatment increased the bodyweight and decreased the HW/BW ratio in the MI rats. The status of lipids was reduced, and HDL was elevated in the CSP-AIso-NCs administered to MI rats. CSP-AIso-NCs decreased the LVEDs, LVEDd, and NT-proBNP and increased the LVEF level. The oxidative stress markers were decreased, and the antioxidants were increased by the CSP-AIso-NCs treatment in the MI rats. The Na+ and Ca+ ions were reduced, and the K+ ions were increased by the CSP-AIso-NCs. The interleukin-1β and tumor necrosis factor-α were also depleted, and Nrf-2 was improved in the CSP-AIso-NCs administered to MI rats. The histological study revealed the ameliorative effects of CSP-AIso-NCs. Overall, our outcomes revealed that the CSP-AIso-NCs are effective against the ISO-induced MI rats. Hence, it could be a hopeful therapeutic nanomedicine for MI treatment.

In an experimental myocardial infarction model, L-arginine pre-intervention may exert cardioprotective effects by regulating OTULIN levels and mitochondrial dynamics.

The experimental myocardial infarction (MI) model originating from isoproterenol (ISO) is frequently preferred in research due to its similarity to MI-induced damage in humans. Beneficial effects of L-arginine (L-Arg), a semi-essential amino acid, in cardiovascular diseases have been shown in many studies. This study was carried out to determine whether L-Arg pre-intervention has protective effects on heart tissue in the experimental MI model. The 28 rats used in the study were randomly divided into 4 equal groups: control, L-Arg, ISO, and L-Arg+ISO. Upon completion of all applications, cardiac markers in serum and biochemical, histopathological, and immunohistochemical examinations in cardiac tissues were performed. Cardiac markers, histopathological changes, oxidative stress, inflammation, and apoptosis were increased in the experimental MI model. In addition, administration of ISO deregulated OTULIN levels and mitochondrial dynamics in heart tissue. However, L-Arg pre-intervention showed a significant protective effect against changes in ISO-induced MI. L-Arg supplementation with cardioprotective effect may reduce the risks of possible pathophysiological processes in MI.

Cardioprotective effects of Schisantherin A against isoproterenol-induced acute myocardial infarction through amelioration of oxidative stress and inflammation via modulation of PI3K-AKT/Nrf2/ARE and TLR4/MAPK/NF-κB pathways in rats

Background and aimsThe scientific community is concerned about cardiovascular disease mortality and morbidity, especially myocardial infarction (MI). Schisantherin A (SCA), a dibenzocyclooctadiene lignan monomer found in S. chinensis fruits has cardiovascular advantages such as increasing NO production in isolated rat thoracic aorta and reducing heart damage caused by ischemia-reperfusion (I/R) through decreasing apoptosis. The present study was undertaken to explore the potential effects of SCA on ISO-induced myocardial infarction in rats.MethodsRats were randomly allocated to four groups: control; ISO-treated, and two additional groups of ISO + SCA (5 or 10 mg/kg body weight). All SCA-treated groups were administered with SCA for 20 days and all ISO groups were challenged with ISO on days 19 and 20.ResultsSCA significantly attenuated ISO-induced rise in heart/body weight ratio, myocardial infarct size, and cardiac functional biomarkers (CK-MB, cTnI and BNP). SCA pre- and co-treatment resulted in a significant reduction in oxidative stress (via MDA, NO and GSH and increased activities of SOD, CAT and GPx) and inflammation (via decreased levels of TNF-α, IL-6 and IL-1β) markers when compared to the same levels in cardiac tissue of ISO-treated rats. This study also showed that SCA protects ISO-induced oxidative stress and inflammation by activating the PI3K-AKT/Nrf2/ARE pathway and suppressing TLR4/MAPK/NF-κB pathways. Furthermore, SCA treatment protected histopathological alterations observed in only ISO-treated cardiac transverse sections of rats.ConclusionIn conclusion, the findings of this study suggest that SCA protects against cardiac injury in the ISO-induced MI model of rats.

Curdione inhibits ferroptosis in isoprenaline-induced myocardial infarction via regulating Keap1/Trx1/GPX4 signaling pathway.

Myocardial infarction (MI) is a common disease with high morbidity and mortality. Curdione is a sesquiterpenoid from Radix Curcumae. The current study is aimed to investigate the protective effect and mechanism of curdione on ferroptosis in MI. Isoproterenol (ISO) was used to induce MI injury in mice and H9c2 cells. Curdione was orally given to mice once daily for 7 days. Echocardiography, biochemical kits, and western blotting were performed on the markers of cardiac ferroptosis. Curdione at 50 and 100 mg/kg significantly alleviated ISO-induced myocardial injury. Curdione and ferrostatin-1 significantly attenuated ISO-induced H9c2 cell injury. Curdione effectively suppressed cardiac ferroptosis, evidenced by decreasing malondialdehyde and iron contents, and increasing glutathione (GSH) level, GSH peroxidase 4 (GPX4), and ferritin heavy chain 1 expression. Importantly, drug affinity responsive target stability, molecular docking, and surface plasmon resonance technologies elucidated the direct target Keap1 of curdione. Curdione disrupted the interaction between Keap1 and thioredoxin1 (Trx1) but enhanced the Trx1/GPX4 complex. In addition, curdione-derived protection against ISO-induced myocardial ferroptosis was blocked after overexpression of Keap1, while enhanced after Keap1 silence in H9c2 cells. These findings demonstrate that curdione inhibited ferroptosis in ISO-induced MI via regulating Keap1/Trx1/GPX4 signaling pathway.

Enhancements of Bcl-2/mTOR/ERK1/2 activities by antioxidant mechanisms confer cardioprotection on Ginkgo biloba supplement against isoprenaline-induced myocardial infarction in rats

BackgroundMyocyte necrosis and apoptosis can be severely induced by acute adrenergic stimulation due to the activation of several cell signalling pathways. However, uncertainty exists regarding the potential cardioprotective effects of Ginkgo biloba (GBS), a Chinese herbal supplement rich with antioxidants, on isoprenaline (ISO)-induced myocardial infarction. Therefore, this work was designed to investigate the cardioprotective mechanisms of GBS on ISO-induced myocardial infarction. MethodsAnimals were selected into four groups. Groups 1 and 2 were pre-treated with normal saline (10 mL/kg i.p) for 28 days. Groups 3 and 4 received GBS (50 mg/kg, i.p) for 28 days. However, groups 2 and 4 were administered ISO (150 mg/kg, s.c) on days 27 and 28 respectively. Following the end of 28-day experiment, animals were euthanised and serum as well as heart tissue were harvested and processed for biochemical and histological examinations. ResultsOur results showed that ISO induced cardiac necrosis, evidenced by increased levels of cardiac injury enzymes (LDH, GGT, CK-MB and cT-1), oxidative stress markers such as GSH, SOD, and CAT levels were significantly reduced while MDA and nitrite concntration were significantly increased. Inflammatory cytokines (IL-6 and TNF-α) were significantly increased while decreasing Bcl-2, mTOR and ERK1/2 cardiac immuno-expressions. Moreso, histological investigation revealed degeneration of cardiomyofibres together with patchy necrosis. However, pre-treatment with GBS significantly inhibited apoptotic processes evidenced by increased antioxidant-mediated activation of Bcl-2, mTOR and ERK1/2. GBS also suppressed the release of cardiac injury enzymes and histological changes were significantly improved. ConclusionGBS protects myocardium against ISO-induced infarction by mechanisms related to antioxidant-mediated by enhancement of Bcl-2/mTOR/ERK1/2 activities.

Inhibition of Pyruvate kinase M2 (PKM2) by shikonin attenuates isoproterenol-induced acute myocardial infarction via reduction in inflammation, hypoxia, apoptosis, and fibrosis.

Myocardial infarction (MI) is a major cause of mortality and disability globally. MI results from acute or chronic myocardial ischemia characterized by an imbalance of oxygen demand and supply, leading to irreversible myocardial injury. Despite several significant efforts in the understanding of MI, the therapy of MI is not satisfactory due to its complicated pathophysiology. Recently, therapeutic potential of targeting pyruvate kinase M2 (PKM2) has been postulated in several cardiovascular diseases. PKM2 gene knockout and expression studies implicated the role of PKM2 in MI. However, the effects of pharmacological interventions targeting PKM2 have not been investigated in MI. Therefore, in the present study, effect of PKM2 inhibitor has been investigated in the MI along with elucidation of possible mechanism(s).MI in rats was induced by administrations of isoproterenol (ISO) at a dose of 100mg/kg s.c. for two consecutives days at 24-h interval. At the same time, shikonin (PKM2 inhibitor) was administered at 2 and 4mg/kg in ISO-induced MI rats. After the shikonin treatment, the ventricular functions were measured using a PV-loop system. Plasma MI injury markers, cardiac histology, and immunoblotting were performed to elucidate the molecular mechanism.Treatment of shikonin 2 and 4mg/kg ameliorated cardiac injury, reduced infarct size, biochemical alterations, ventricular dysfunction, and cardiac fibrosis in ISO-induced MI. Expression of PKM2 in the ventricle was reduced while PKM1 expression increased in the shikonin treated group, indicating PKM2 inhibition restores PKM1 expression. In addition, PKM splicing protein (hnRNPA2B1 & PTBP1), HIF-1α, and caspase-3 expression were reduced after shikonin treatment.Our findings suggest that pharmacological inhibition of PKM2 with shikonin could be a potential therapeutic strategy to treat MI.

Cardioprotective Effect of Flibanserin against Isoproterenol-Induced Myocardial Infarction in Female Rats: Role of Cardiac 5-HT2A Receptor Gene/5-HT/Ca2+ Pathway.

Myocardial infarction (MI) is a life-threatening ischemic disease and is one of the leading causes of morbidity and mortality worldwide. Serotonin (5-HT) release during myocardial ischemia plays an important role in the progression of myocardial cellular injury. This study was conducted to investigate the possible cardioprotective effect of flibanserin (FLP) against isoproterenol (ISO)-induced MI in rats. Rats were randomly divided into five groups and were treated orally (p.o.) with FLP (15, 30, and 45 mg/kg) for 28 days. ISO was administered subcutaneously (S.C.) (85 mg/kg) on the 27th and 28th days to induce MI. ISO-induced myocardial infarcted rats exhibited a significant increase in cardiac markers, oxidative stress markers, cardiac and serum 5-HT levels, and total cardiac calcium (Ca2+) concentration. ISO-induced myocardial infarcted rats also revealed a remarkable alteration of electrocardiogram (ECG) pattern and significantly upregulated expression of the 5-Hydroxytryptamine 2A (5-HT2A) receptors gene. Moreover, ISO-induced myocardial infarcted rats showed significant histopathological findings of MI and hypertrophic signs. However, pretreatment with FLP significantly attenuated the ISO-induced MI in a dose-dependent manner, as the effect of FLP (45 mg/kg) was more pronounced than that of the other two doses, FLP (15 and 30 mg/kg). The present study provides evidence for the cardioprotective efficacy of FLP against ISO-induced MI in rats.

EXPLORATION OF CARDIOPROTECTIVE AND ANTIOXIDANT ACTION OF BILIRUBIN IN ISOPRENALINE-INDUCED ISCHEMIA MODEL OF MALE WISTAR ALBINO RATS

Objectives: Ischemic heart disease is one of the leading causes of death worldwide. Bilirubin, an endogenous product of heme catabolism, has remarkable antioxidant properties. This study was planned with an aim to evaluate cardioprotective potential of bilirubin in isoprenaline (ISO)- induced rat myocardial ischemia model. Methods: In this study, a total of 24 adult male Wistar albino rats (200–250 g) were divided into four groups of six rats each. Groups I, III, and IV, respectively, received distilled water (10 mL/kg bw), bilirubin (40 mg/kg bw), and bilirubin (60 mg/kg bw) intraperitoneally (i.p.) for 21 days. Along with that, Groups III and IV received ISO (85 mg/kg bw) subcutaneously (s.c.) on 20th and 21st day. Group II received ISO (85 mg/kg bwi. p.) on 20th and 21st day. After 24 h of ISO administration, rats were sacrificed and biochemical and histopathological parameters were assessed. These parameters were evaluated: Cardiac biomarkers-lactate dehydrogenase (LDH) and creatine kinase (CK-MB) and antioxidant-glutathione reductase (GR). Isolated heart specimens were processed for light microscopy. Results: Administration of bilirubin in Groups III and IV significantly prevented ISO-induced elevation of CK-MB and LDH levels as compared to Group II. Furthermore, there is a significant increase in the levels of GR in Groups III and IV compared to Group II. These changes were significantly higher in Group IV (high dose) compared to Group III (low dose). Light microscopic findings of the myocardium in bilirubin-treated group revealed a well preserved normal morphology of cardiac muscle with minimal evidence of myocardial injury as compared to ISO-treated hearts. Conclusion: Pre-administration with bilirubin is protective against ISO-induced myocardial infarction. This beneficial effect is most likely due to its antioxidant property. This study may trigger interest toward the use of bilirubin as a cardioprotective agent in myocardial infarction.

Cardioprotective Effects of Aconite in Isoproterenol-Induced Myocardial Infarction in Rats.

Myocardial infarction (MI) is a severe clinical condition caused by decreased or complete cessation of blood flow to a portion of the myocardium. Aconite, the lateral roots of Aconitum carmichaelii Debx., is a well-known Chinese medicine for treatment of heart failure and related cardiac diseases. The present study is aimed at investigating the cardioprotective effect of aconite on isoproterenol- (ISO)- induced MI. The qualitative analysis of aqueous extracts from brained aconite (AEBA) was conducted by HPLC. A rat model of MI induced by ISO was established to examine the effects of AEBA. The cardiac function was assessed by echocardiography. The serum levels of SOD, CK-MB, cTnT, and cTnI were detected to estimate myocardial injury. The pathological changes of heart tissue were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and Masson's trichrome staining. The expressions of abnormal vascular remodeling and hypoxia-related components and the levels of inflammation-associated genes and proteins were detected by RT-qPCR, western blotting, and immunofluorescence. The contents of benzoylaconine, benzoylmesaconine, benzoylhypacoitine, and hypaconitine in AEBA were 1.35 μg/g, 37.35 μg/g, 57.10 μg/g, and 2.46 μg/g, respectively. AEBA obviously improved heart function through promoting echocardiographic parameters, radial strain, and circumferential strain. The data of TTC staining, HE staining, and Masson's trichrome staining disclosed that AEBA could significantly reduce infarct size, inhibit inflammatory cell infiltration, and decrease the myocardial fibrosis. Moreover, AEBA distinctly suppressed the serum levels of SOD, MDA, CK-MB, cTnT, and cTnI in ISO-induced rats. The results of RT-qPCR indicated that AEBA inhibited the expressions of hypoxia- and inflammation-related genes, including VEGF, PKM2, GLUT-1, LDHA, TNF-α, IL-1β, IL-6, and COX2. In addition, the western blotting and immunofluorescence analyses further confirmed the results of RT-qPCR. In summary, our results indicate that the AEBA could improve ISO-induced myocardial infarction by promoting cardiac function, alleviating myocardial hypoxia, and inhibiting inflammatory response and fibrosis in heart tissue.

Ciprofol attenuates the isoproterenol-induced oxidative damage, inflammatory response and cardiomyocyte apoptosis.

Background and Purpose: Ciprofol (HSK3486), a novel 2,6-disubstituted phenol derivative, is a new intravenous anesthetic compound with a similar chemical structure to propofol. Animal studies have also shown that propofol plays a protective role in a variety of cardiovascular diseases, including myocardial infarction, myocardial ischemia-reperfusion injury and takotsubo syndrome. However, whether ciprofol exerts cardioprotective effects on myocardial infarction remains unclear. Thus, the aim of this work was to explore the potential cardioprotective mechanism of ciprofol on isoproterenol (ISO)-induced myocardial infarction. Experimental Approach: In the present study, male C57BL/6 mice were subjected to subcutaneous injection of ISO (100mg/kg) for 2 consecutive days to induce experimental myocardial infarction. Herein, we found that ciprofol could inhibit the abnormal increase in myocardial injury enzymes, the area of myocardial infarction and cardiac dysfunction in ISO-treated mice. Ciprofol administration increased the activity of superoxide dismutase and reduced the levels of NADPH oxidase and malondialdehyde in ISO-treated hearts. Additionally, ciprofol administration markedly reduced the expression of pro-inflammatory cytokines and cardiomyocyte apoptosis. In an in vitro model, the results also confirmed that ciprofol could inhibit ISO-induced oxidative damage, the inflammatory response and cardiomyocyte apoptosis. Moreover, ciprofol can activate the sirtuin1 (Sirt1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and Sirt1 and Nrf2 inhibition almost abolished ciprofol-mediated cardioprotective effects. Interpretation: Ciprofol protects the heart against ISO-induced myocardial infarction by reducing cardiac oxidative stress, the inflammatory response and cardiomyocyte apoptosis.

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.

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.

A novel synthetised sulphonylhydrazone coumarin (E)-4-methyl-N'-(1-(3-oxo-3H-benzo[f]chromen-2- yl)ethylidene)benzenesulphonohydrazide protect against isoproterenol-induced myocardial infarction in rats by attenuating oxidative damage, biological changes and electrocardiogram.

Coumarins and their derivatives are becoming a potential source for new drug discovery due to their vast array of biological activities. The present study was designed to investigate the cardioprotective effects of a newly synthesised coumarin, symbolised as 5,6-PhSHC, against cardiac remodelling process in isoproterenol (ISO) induced myocardial infarction (MI) in male Wistar rats by evaluating haematological, biochemical and cardiac biomarkers. Rats were pre/co-treated with 5,6-PhSHC or clopidogrel (150 μg/kg body weight) daily for a period of 7 days and then MI was induced by injecting ISO (85 mg/kg body weight), at an interval of 24 hours for 2 consecutive days, on the sixth and seventh days. The in vivo exploration indicated that the injection of 5,6-PhSHC improved the electrocardiographic (ECG) pattern and prevented severe heart damage by reducing leakage of the cardiac injury markers, such as troponin-T (cTn-T), lactate dehydrogenase (LDH), and creatine kinase-MB. The cellular architecture of cardiac sections, altered in the myocardium of infracted rats, was reversed by 5,6-PhSHC treatment. Results showed that injection of 5,6-PhSHC elicited significant cardioprotective effects by prevention of myocardium cell necrosis and inflammatory cells infiltration, along with marked decrease in plasma levels of fibrinogen. In addition, the total cholesterol, triglyceride, LDL-c, and HDL profiles underwent remarkable beneficial changes. It was also interesting to note that 5,6-PhSHC enhanced the antioxidative defence mechanisms by increasing myocardial glutathione (GSH) level, superoxide dismutase (SOD), and catalase (CAT) activities, together with reducing the levels of thiobarbituric-acid-reactive substances (TBARS), when compared with ISO-induced rats. Taken together, these findings suggested a beneficial role for 5,6-PhSHC against ISO-induced MI in rats. Furthermore, in silico analysis showed that 5,6-PhSHC possess high computational affinities (E-value >-9.0kcal/mol) against cyclooxygenase-2 (PDB-ID: 1CX2), vitamin K epoxide reductase (PDB-ID: 3KP9), glycoprotein-IIb/IIIa (PDB-ID: 2VDM) and catalase (PDB-ID: 1DGF). Therefore, the present study provided promising data that the newly synthesised coumarin can be useful in the design and synthesis of novel drug against myocardial infarction.