ISO-induced Myocardial Infarction In Rats Research Articles

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, BAOAg- 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 as well as 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.

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.

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.

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.

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.

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.

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

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

Alpha-terpineol prevents myocardial damage against isoproterenol-MI induced in Wistar-Kyoto rats: new possible to promote cardiovascular integrity

Alpha-terpineol (TPN) is one of the major components of the resin obtained from Protium heptaphyllum. This plant has been utilized as medicine by Brazilian indigenous tribes to treat cardiovascular diseases. Scientific reports have shown that the TPN possesses vasorelaxant and antihypertensive effects. This study was conducted to assess the cardioprotective action of TPN against isoproterenol (ISO)-induced cardiotoxicity. Wistar rats were randomly divided into six groups. Rats were orally administered with TPN (25, 50, and 75 mg/kg, respectively) for 15 days, and ISO was administered (85 mg/kg, subcutaneously) on the 14th and 15th days. At the end of the experiment, the hemodynamic, baroreflex test, ECG, biochemical, histological, and morphometric changes were monitored from control and experimental groups, i.e., on the 15th day. ISO-induced myocardial infarcted rats showed an increase in mortality rates, cardiac marker enzymes, tachycardia, hypertrophy, myocardium necrosis, edema, hemorrhagic areas, infiltration of inflammatory cells like lymphocytes, and increased myocardial infarct size. However, pretreatment with TPN significantly inhibited these effects of ISO. The histopathological findings obtained for the myocardium further confirmed the biochemical results. Thus, the present study provides evidence for the efficacy of TPN against ISO-induced myocardial infarction in rats.

Boeravinone B alleviates gut dysbiosis during myocardial infarction-induced cardiotoxicity in rats.

Myocardial infarction (MI) is the most common heart disease, and also, it is one of the leading causes of death from cardiovascular disease. It is well known that MI causes additional injury during blood flow restoration in ischaemic myocardium. Boeravinone B (BB) is a well‐known antioxidant and anti‐inflammatory drug. We investigated the cardioprotective effect of BB drug against isoproterenol (ISO)‐induced MI in rats in this experimental study, along with we analysed its underlying mechanism. Adult Sprague Dawley (SD) rats were treated subcutaneously with ISO (45 mg/kg), then divided into groups and then given BB drug was administered orally. The cardioprotective effect of BB on ISO‐induced MI rats was analysed by estimating the heart injury markers, antioxidant pro‐inflammatory cytokines and inflammatory parameters. We also detected quantified expression of inflammation and apoptosis‐related marker protein family. We estimated the effect of BB drug on GUT microbiota in ISO‐induced MI rats and scrutinized the histopathological variations in heart tissues. BB treatment significantly (P < .001) diminished the level of heart markers such as lactate dehydrogenase (LDH), troponin (TnT), creatine kinase (CK) and creatine kinase isoenzymes MB (CK‐MB). BB treatment also altered the antioxidant parameters and reduced the pro‐inflammatory cytokines in the serum and tissues. Additionally, the histopathological aspects demonstrated that the pathological changes observed in the heart tissue of the ISO group rats were suppressed by the BB treatment to varying degrees. Furthermore, the expressions of caspase‐3, p53, caspase‐9, Bax, interleukin‐6 (IL‐6), cytochrome C, neutrophil gelatinase‐associated lipocalin (NGAL), tumour necrosis factor‐α (TNF‐α), nuclear factor kappa B (NF‐κB) and interleukin‐1β (IL‐1β) in the heart tissue were down‐regulated whereas the Bcl‐2 expression seemed to be enhanced. BB treatment not only alleviated ISO‐induced gut dysbiosis by its enhanced specified Firmicutesto‐Bacteroidetes (F/B) ratio but also maintained the relative abundance of major bacteria such as Clostridium IV, Butyricicoccus, Clostridium XIVs, Akkermansia and Roseburia. Collectively, our findings showed that the BB drug acted against myocardial infraction and prevented the damage by reducing the oxidative stress and controlling the inflammatory pathways, and gut microbiota.

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

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

Ameliorative effect of ferruginol on isoprenaline hydrochloride‐induced myocardial infarction in rats

Cardiovascular-related diseases continue to be a leading cause of death globally. Among ischemic-induced cardiac diseases, myocardial infarction (MI) is reported to be of an alarming value. Despite numerous improvements in the medical intrusions, still this armamentarium fails to be effective in managing the illness without setbacks. Ferruginol (FGL) is a major polyphenols and terpenoids with numerous pharmacological activities including antioxidant and anti-inflammatory. Following, this work was aimed to explore the cardio protective effect of FGL (50 mg/kg) in isoprenaline hydrochloride (ISO)-induced MI in experimental rats. After treatment with FGL in ISO-induced MI in rats, noticeable changes were observed in the experimental rats. Injection of ISO to rats resulted in the augmented cardiac weight, serum cardiac markers (creatine kinase, creatine kinase-MB, cardiac troponin T, and Cardiac troponin I), lipid peroxidation end products (thiobarbituric acid-reactive substance and lipid hydroperoxides), reduced endogenous antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione), reduced ATPase activity, and escalated pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-α, and nuclear factor-κB) levels. Interestingly, the FGL supplementation to the ISO-treated rats revealed the diminished heart weight, reduced cardiac markers, and lipid peroxidation. FGL also possessed the improved antioxidants status and diminished pro-inflammatory mediator levels. The outcomes of histological analysis also evidenced the cardio protective role of FGL. Treatment with FGL reduced the cardiac damage biomarkers maintained to near normal levels in ISO-induced rats. These study findings disclose the prospective capability of FGL in the treatment of MI in the future.

Therapeutic Potential of Biochanin-A Against Isoproterenol-Induced Myocardial Infarction in Rats.

This study determined the effect of Biochanin A (BCA) on isoproterenol (ISO) induced Myocardial Infarction (MI) in male Wistar rats. Animals (weighing 150-180 g) were divided into four groups, with six animals in each group and pretreated with BCA (10mg/kg Body Weight [BW]) and ɑ-tocopherol (60mg/kg BW) for 30 days; and ISO (20mg/kg BW) was administrated subcutaneously on the 31st and 32nd day. ISO-induced MI rats demonstrated the significant elevation of serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, lactate dehydrogenase, creatine kinase-MB and cardiac troponin; however, concomitant pretreatment with BCA protected the rats from cardiotoxicity caused by ISO. Activities of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase significantly reduced in the heart with ISO-induced MI. Pretreatment with BCA produced a marked reversal of these antioxidant enzymes related to MI-induced by ISO. In conclusion, this study suggested that BCA exerts cardioprotective effects through modulating lipid peroxidation, enhancing antioxidants, and detoxifying enzyme systems.

Arbutin prevents alterations in mitochondrial and lysosomal enzymes in isoproterenol-induced myocardial infarction: An in vivo study.

The present study demonstrated the protective effects of arbutin (ARB) on hyperlipidemia, mitochondrial, and lysosomal membrane damage and on the DNA damage in rats with isoproterenol (ISO)-induced myocardial infarction (MI). Rats were pretreated with ARB (25 and 50 mg/kg body weight (bw)) for 21 days. After pretreatment with ARB, MI was induced by subcutaneous injection of ISO (60 mg/kg bw) for two consecutive days at an interval of 24 h. The levels of TC, TG, and FFA were increased and decreased the level of PL in the heart tissue of ISO-induced MI rats. Very-low-density lipoprotein cholesterol and low-density lipoprotein cholesterol were increased while high-density lipoprotein cholesterol was decreased in the plasma of ISO-administered rats. A heart mitochondrial fraction of the ISO rats showed a significant decrease in the activities of mitochondrial enzymes isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase. The activities of lysosomal enzymes (β-glucosidase, β-glucuronidase, α-galactosidase, β-galactosidase, cathepsin-B, and cathepsin-D) were increased significantly in the heart tissue homogenate of disease control rats. In ISO-induced MI, rat's significant increase in the percentage of tail DNA and tail length, and a decrease in the level of head DNA were also observed. ARB administration to MI rats brought all these parameters to near normality, showing the protective effect of ARB against MI in rats. The results of this study demonstrated that the 50 mg/kg bw of ARB shows higher protection than 25 mg/kg bw against ISO-induced damage.

Bridelia ferruginea Inhibit Rat Heart and Liver Mitochondrial Membrane Permeability Transition Pore Opening Following Myocardial Infarction

Despite advances in therapy, myocardial infarction (MI) remains a leading cause of death worldwide. Recently, the mitochondrion has been targeted in cardio-protection due to its role in reperfusion injury after MI. Similarly, the mitochondrion has been reported to play critical role in cardiovascular disease-associated liver dysfunctions. Medicinal plants are used in the treatment of cardiovascular diseases in Nigeria Ethnomedicine, particularly Bridelia ferruginea (BF). The study explored the effect of aqueous leaves extract of BF (AEBF) as heart and liver mitochondrial permeability transition (mPT) pore opening inhibitor using Isoprenaline-hydrochloride (ISO)-induced MI rat model. Twenty rats were used in the study, while eight were orally and daily pretreated for 14 days with 200 or 400 mg/kg of AEBF before intraperitoneal injection of ISO (100 mg/kg) for 2 days at 24 h interval. The mPT pore opening was spectrophotometrically assessed under sodium succinate energized condition at 540 nm. Results: The AEBF at 200 and 400 mg/kg decreased elevated plasmatic creatine kinase, lactate dehydrogenase and aspartate aminotransferase in ISO-induced MI in rats. Similarly, increased heart and liver lipid peroxides were inhibited by AEBF. The mPT pore opening of ISO-induced MI in rat heart was inhibited by AEBF and this impacted positively on the liver mPT pore. Furthermore, histologic examinations showed that 400 mg/kg AEBF pretreatment showed absence of lesions and necrotic cells. Conclusion: Taken together AEBF protected the heart and liver of ISO-induced MI in rats via inhibition of mPT pore opening. Hence, this may be relevant in cardio- and hepato-protection.

THE POTENTIAL OF HIBISCUS SABDARIFFA LINN. (ROSELLE) POLYPHENOL-RICH EXTRACT AS A CARDIOPROTECTIVE AGENT IN MYOCARDIAL INFARCTION MODEL

Myocardial infarction (MI) is a common cause of death due to interrupted blood supply to the heart. Roselle calyx (Hibiscus sabdariffa Linn.) is rich in polyphenols and has a potential in alleviating the risk of cardiovascular disease through its antioxidant activity. This study was aimed to investigate the effects of Hibiscus sabdariffa Linn. or roselle polyphenol-rich extract (HPE) supplementation in oxidative stress and cardiac injury biomarkers as well as cardiac histological changes following isoprenaline (ISO)-induced myocardial infarction (MI). Twenty-one male rats were randomly divided into three groups: control, MI, and HPE+MI. Normal saline or HPE (20 mg/kg BW) was given to MI and HPE+MI groups, respectively, for 14 consecutive days via force feeding. On the 15th and 16th day, 85 mg/kg body weight of ISO was administered subcutaneously to induce MI. Control group was only given normal saline throughout this 16-day duration of study. The results showed that HPE reduced the oxidative stress markers malondialdehyde (MDA) and nitrite oxide (NO) in HPE+MI group when compared with MI group (p&lt;0.05) while increased reduced glutathione (GSH) level reflexes the improvement in antioxidant status. Cardiac injury biomarkers analysis showed no significant difference in HPE+MI group when compared to MI group. Histological study showed that HPE managed to reduce cardiac muscle fibre damage and infiltration of inflammatory cells in ISO-induced MI rats. In conclusion, HPE has the potential in protecting the heart against ISO-induced MI by reducing the oxidative stress and increasing antioxidant status.

Curcumin Nanoparticles Protect against Isoproterenol Induced Myocardial Infarction by Alleviating Myocardial Tissue Oxidative Stress, Electrocardiogram, and Biological Changes.

Curcumin from Curcuma longa is a nutraceutical compound reported to possess strong antioxidant activity that makes it a candidate for use in counteracting oxidative stress-induced damage. The effect of pre-treatment with curcumin nanoparticles (nC) compared to conventional curcumin (Cs) on blood pressure, electrocardiogram, and biological changes on isoproterenol (ISO)-induced myocardial infarction (MI) in rats had been investigated. The Cs doses of 150 and 200 mg/kg bw and all nC doses (100, 150 and 200 mg/kg bw) significantly reduced heart rate before ISO administration and prevented QRS complex enlargement after MI induction (p < 0.026). All doses of Cs and nC prevented prolongation of the QT and QT corrected (QTc) intervals, with better results for higher doses (p < 0.048). The nC solution had more significant results than Cs in all metabolic parameters assessed (lactate dehydrogenase, glycaemia, aspartate transaminase, and alanine transaminase, p < 0.009). nC was more efficient than Cs in limiting myocardial oxidative stress and enhancing antioxidative capacity (p < 0.004). Compared to Cs, nC better prevented myocardial damage extension, reduced interstitial oedema, and inflammation. Curcumin nanoparticles as compared to conventional curcumin exert better antioxidative effects. Moreover, nC better prevent cardiomyocytes damage, and electrocardiogram alterations, in the case of ISO-induced MI in rats.

Cardioprotective Activity of Agaricus bisporus Against Isoproterenol- Induced Myocardial Infarction in Laboratory Animals

Background: Agaricus bisporus (A. bisporus) is an edible basidiomycete mushroom native to grasslands in Europe and North America. A. bisporus, commonly known as white button mushroom (WBM), is widely cultivated in most countries, and it constitutes the bulk of all mushrooms consumed in the United States and Australia. Traditionally this fungus has used in the treatment of heart diseases. Also it has anti-ageing property.Mushrooms have been found effective against cancer, cholesterol reduction, stress, insomnia, asthma, allergies and diabetes. Objective: The present research was designed to appraise the cardioprotective activity of a hydroalcoholic extract of Agaricus bisporus (EEAB) on Isoproterenol (ISO) induced myocardial infarction (MI) in Albino Wistar rat. Traditionally, Agaricus bisporus is reported in the treatment of heart diseases, cancer, cerebral stroke and anti-ageing property. Materials and Methods: Wistar rats of different sex were randomly split into five groups namely positive control, negative control, standard, test-1 and test-2 and received distilled water, ISO (85 mg/kg), Simvastatin (10 mg/kg/day, oral) and EEAB (200 and 400 mg/kg/day, p.o.) for 30 days, respectively. MI was induced in rats by ISO at an interval of 24 hrs on 31 and 32 day and on the next day, blood was amassed through retro-orbital plexus for the assessment of biochemical markers (cholesterol, lowdensity lipoprotein, high-density lipoprotein, very low-density lipoprotein, triglycerides, alanine aminotransferase and total protein) and finally, the rats were immolated by cervical dislocation. The heart tissue was reaped instantly, cleaned with chilled isotonic saline and clasped in 10% buffered formalin and used for the histopathological analysis. Results: ISO p.o. administration significantly elevated the cholesterol, low density lipoprotein, very low density lipoprotein, triglycerides, alanine aminotransferase and aspartate aminotransferase levels while it decreases high-density lipoprotein and total protein in plasma and administration of EEAB decreases the level of cholesterol, low-density lipoprotein, very low-density lipoprotein, triglycerides, alanine aminotransferase and aspartate aminotransferase levels while it increases high-density lipoprotein and total protein levels. Pretreatment with EEAB protected the cardiotoxicity induced by ISO. The histopathological findings support the analysis of biochemical parameters, ISO-induced myocardium showed infracted zone with edema, inflammatory cells, lipid droplets, myocardial necrosis and vacuolization of myofibrils which were reduced. Conclusion: It can be an outcome that EEAB possessed cardioprotective activity against experimental and clinical studies of ISO-induced myocardial infarction in rats.

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

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

Formononetin attenuates isoproterenol‐induced cardiac toxicity in rats owing to its antioxidant, anti‐inflammatory and anti‐apoptotic activity

IntroductionA high rate of mortality and morbidity is associated with myocardial infarction (MI), indicating a need to hunt for newer treatment modalities. Formononetin (FMN) is a dietary flavonoid with remarkable antioxidant and anti‐apoptotic properties. Therefore, the aim of this study was to evaluate the ability of FMN in attenuating isoproterenol (ISO) induced oxidative stress and myocardial infarction.MethodsA total of 48 Male Wistar rats were administered either FMN (5, 10 or 20 mg/kg/day, i.p.) or vehicle for 15 days along with subcutaneous ISO, 85 mg/kg for 2 consecutive days i.e. 13th and 14th days. On the 15th day, rats were anaesthetized followed by cannulation of right coronary artery to record hemodynamic parameters. Blood sample was collected and heart was excised to evaluate for biochemical, histopathological, ultrastructural and immuohistochemical studies.ResultsISO‐treated rats demonstrated disturbed hemodynamic. There was also a significant decrease in antioxidant enzyme levels and increase in the level, of malondialdehyde, serum TNF‐α and IL‐6. The cardiac injury markers like creatine kinase‐MB and lactate dehydrogenase were increased in the serum. Additionally, immunohistochemistry displayed an increased Bax/Bcl‐2 ratio in the myocardium. Histopathological and ultrastructural studies support the protective effect of FMN in ISO‐induced myocardial infarcted rats.ConclusionFMN alleviates myocardial damage in ISO induced cardiac injury by preserving hemodynamic and biochemical function and reducing inflammation due to its anti‐apoptotic, anti‐inflammatory and antioxidant activities.Support or Funding InformationThe Project has been funded by the AIIMS, DelhiThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.