Isoproterenol-induced Myocardial Infarction In Rats Research Articles

Cardioprotective effects of p-coumaric acid on tachycardia, inflammation, ion pump dysfunction, and electrolyte imbalance in isoproterenol-induced experimental myocardial infarction.

Cardiovascular diseases cause a large number of deaths throughout the world. No research was conducted earlier on p-coumaric acid's effect on tachycardia, inflammation, ion pump dysfunction, and electrolyte imbalance. Hence, we appraised the above-said parameters in isoproterenol-induced myocardial infarcted rats. This investigation included 24 male albino Wistar rats in 4 groups. Normal control Group 1, p-coumaric acid (8 mg/kg body weight) alone treated Group 2, Isoproterenol (100 mg/kg body weight) induced myocardial infarcted Group 3, p-coumaric acid (8 mg/kg body weight) pretreated isoproterenol (100 mg/kg body weight) induced Group 4. After 1 day of the last dose of isoproterenol injection (day 10), rats were killed and blood and heart were taken and inflammatory markers, lipid peroxidation, nonenzymatic antioxidants, ion pumps, and electrolytes were measured. The heart rate, serum cardiac troponin-T, serum/plasma inflammatory markers, and heart proinflammatory cytokines were raised in isoproterenol-induced rats. Isoproterenol also enhanced plasma lipid peroxidation, lessened plasma nonenzymatic antioxidants, and altered heart ion pumps and serum and heart electrolytes. In this study, p-coumaric acid pretreatment orally for 7 days to isoproterenol-induced myocardial infarcted rats prevented changes in the above-cited parameters. p-Coumaric acid's anti-tachycardial, anti-inflammatory, anti-ion pump dysfunction and anti-electrolyte imbalance properties are the mechanisms for these cardioprotective effects.

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

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.

Cardioprotective activity of Apples Juice on Isoproterenol-Induced Myocardial Infarction in Rat

Myocardial infarction was local necrosis of heart tissue due to reduced oxygen supply because of theocclusion of coronary arteries. Fruits could reduce the risk of developing obesity and CVDs. Severalstudies have shown that apples had a strong cardioprotective effect. This study aimed to understandthe cardioprotective activity of two variants of apples, e.g., Fuji and Malang, on isoproterenol-inducedmale Wistar rats. The cardioprotective activity test was carried out for 14 days, all testing group exceptnegative control, was induced by isoproterenol. The results of testing cardioprotective activity showedthat Fuji Apple juice and Apel Malang juice had the same capability to inhibit increasing cardiacbiomarkers value (CK and CK-MB) with the highest inhibition was 79,56% and 73,08% for FujiApples, 69,18% and 43,04% for Apel Malang. The result of the cardiac histopathology examinationshowed that both Apples could prevent cardiac tissue damage. All juice Apple doses had the samecardioprotective activity.

β-caryophyllene blocks reactive oxygen species-mediated hyperlipidemia in isoproterenol-induced myocardial infarcted rats

Myocardial infarction (MI) is a leading cause of death. Lipid-lowering interventions have been shown to decrease coronary events and mortality of MI and heart failure. In this investigation, we assessed the anti-hyperlipidemic effects of β-caryophyllene in isoproterenol-induced myocardial infarcted rats. β-Caryophyllene (20 mg/kg body weight) pre-and co-treatment was given to rats orally, daily, for 3 weeks. Isoproterenol (100 mg/kg body weight) was administered to rats to induce MI. The levels of serum cardiac troponins T and I, serum and heart total cholesterol, triglycerides, free fatty acids, and the levels of serum low-density and very low-density lipoprotein-cholesterols were augmented, and the level of serum high-density lipoprotein-cholesterol was lessened in myocardial infarcted rats. Further, the activity/levels of liver 3-hydroxy-3-methylglutaryl-coenzyme A reductase and plasma thiobarbituric acid reactive substances were amplified and the activity/levels of heart glutathione –S- transferase, vitamin C, and vitamin E were lessened by isoproterenol. A down-regulated expression of liver sterol regulatory element-binding protein-2 and liver low-density lipoprotein-receptor genes was observed by a reverse transcription-polymerase chain reaction study. Moreover, histopathology of Sudan III staining revealed an accumulation of fats in the heart of isoproterenol-induced rats. Nevertheless, β-caryophyllene pre-and co-treatment blocked alterations in all the parameters examined in isoproterenol-induced rats and inhibited the risk of MI. Moreover, the in vitro study revealed the potent free radical scavenging and antioxidant effects of β-caryophyllene. β-Caryophyllene's antioxidant and anti-hyperlipidemic properties are the possible mechanisms for the observed protective effects in this investigation.

Punicalagin attenuates myocardial oxidative damage, inflammation, and apoptosis in isoproterenol-induced myocardial infarction in rats: Biochemical, immunohistochemical, and in silico molecular docking studies

Myocardial infarction (MI) is a life-threatening ischemic disease and is one of the leading causes of morbidity and mortality worldwide. Punicalagin (PU), the major ellagitannin found in pomegranates, is characterized by multiple antioxidant activities. The aim of this study is to assess the protective effects of PU against isoproterenol (ISO)-induced acute myocardial damage and to investigate its underlying vascular mechanisms using rat model. MethodsRats were randomly divided into five groups and were treated orally (p.o.) with PU (25 and 50 mg/kg) for 14 days. ISO was administered subcutaneously (S.C.) (85 mg/kg) on the 15th and 16th days to induce Myocardial infarction. Cardiac markers, oxidative stress markers, and inflammatory cytokines levels were determined in the heart tissue. Immunohistochemistry analysis was performed to determine the protein expression pathways of inflammation, apoptosis and oxidative stress (Nuclear factor erythroid 2-related factor 2 (Nrf-2), and heme oxygenase-1 (HO-1) in all the groups. In silico study was carried out to evaluate the molecular interaction of PU with some molecular targets. ResultsOur results showed that ISO-induced cardiac tissue injury was evidenced by increased serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), and lactate dehydrogenase (LDH), associated with several histopathological changes. ISO also induced an increase of MDA, PCO, NO, and 8-hydroxy-2-deoxyguanosine (8-OHdG), along with a decrease of antioxidant enzyme activities in the myocardial tissues. In addition, an increase of TNF-α, NF-κB, IL-6, IL-1β, iNOS, Nrf2 and (HO-1) was observed. Pre-treatment with PU reduced myocardial infract area, ameliorated histopathological alterations in myocardium, and decreased activities of myocardial injury marker enzymes in ISO-induced rats. In addition, PU remarkably restored ISO-induced elevation of lipid peroxidation and decrease of antioxidants, significantly reduced myocardial pro-inflammatory cytokines concentrations in this animal model. Molecular docking analysis of PU with protein targets showed potent interactions with negative binding energies.In conclusion, PU can protect the myocardium from oxidative injury, inflammatory response, and cell death induced by ISO by upregulating Nrf2/HO-1 signaling and antioxidants.

Potential combined effect of Spirulina platensis and Momordica charantia fruits on attenuation of isoproterenol-induced myocardial infarction in rats: identification and prediction its mechanism

We established in vivo models of isoproterenol-induced myocardial infarction (MI) to determine the cardioprotective effect of Spirulina platensis (Spi), Momordica charantia fruit (MC) and their combination. MI was induced in six groups of Male Wistar albino with isoproterenol, and cardioprotection was evaluated by measuring SGOT, SGPT, LDH, CK, CK-MB with commercially available test kits and analyzing histopathology. Online PASS was used to predict the mechanism of action of a marker compound in Spi and MC. Rat serum levels of LDH, SGOT, CK-MB, and CK were significantly reduced by the Spi and MC combination extract (P < 0.05). The combination extract at a dose of 50:50 mg/kg body weight preserve the integrity of the myocardial cell membrane. Identified compounds by LC-MS/MS in the ethanol extract of Momordica charantia are (3β,16α-Dihydroxy-lanosta-8,24-dien-21-oic acid), Eclalbasaponin II, Epianhydrobelachinal, Epianhydrobelachinal, Paeonenolide F, Ziyu glycoside II. Identified compounds by LC-MS/MS in Spirulina platensis extract are d-Lirioferine, Lycopodine, Yuanhunine, Candidate Mass C18H26N2O5 and Candidate Mass C36H38N4O5. In PASS analysis, Phycocyanobilin’s cardioprotective mechanism of action is predicted to be kinase inhibitor, cytoprotectant, and platelet aggregation inhibitor, with Probable activities (Pa) of 0.06, 0.53, and 0.443, respectively. The Pa values for cholesterol antagonist, proliferative disease treatment, nitric oxide scavenger, and anti-inflammatory agents in Momordicoside A are respectively 0.841, 0.666, 0.59, and 0.55. These findings suggest that the cardioprotective activity of the combination of Spi and MC extracts at a dose of 50 mg/kg was synergistic.

Antioxidant Flavonoid Diosmetin Is Cardioprotective in a Rat Model of Myocardial Infarction Induced by Beta 1-Adrenergic Receptors Activation.

Myocardial infarction (MI) is a common and life-threatening manifestation of ischemic heart diseases (IHD). The most important risk factor for MI is hypertension. Natural products from medicinal plants have gained considerable attention globally due to their preventive and therapeutic effects. Flavonoids have been found to be efficacious in ischemic heart diseases (IHD) by alleviating oxidative stress and beta-1 adrenergic activation, but the mechanistic link is not clear. We hypothesized that antioxidant flavonoid diosmetin is cardioprotective in a rat model of MI induced by beta 1-adrenergic receptor activation. To test this hypothesis, we evaluated the cardioprotective potential of diosmetin on isoproterenol-induced MI in rats by performing lead II electrocardiography (ECG), cardiac biomarkers including troponin I (cTnI) and creatinine phosphokinase (CPK), CK-myocardial band, (CK-MB), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotranferase (AST) by using biolyzer 100, as well as histopathological analysis. We found that diosmetin (1 and 3 mg/kg) attenuated isoproterenol-induced elevation in the T-wave and deep Q-wave on the ECG, as well as heart-to-body weight ratio and infarction size. In addition, pretreatment with diosmetin attenuated the isoproterenol-induced increase in serum troponin I. These results demonstrate that flavonoid diosmetin may provide therapeutic benefit in myocardial infarction.

Protective effects of β-caryophyllene on mitochondrial damage and cardiac hypertrophy pathways in isoproterenol-induced myocardial infarcted rats

The cardiac mitochondrial damage and cardiac hypertrophy pathways are intimately associated with the pathology of myocardial infarction (MI). The protective effects of β-caryophyllene on mitochondrial damage and cardiac hypertrophy pathways in isoproterenol-induced myocardial infarcted rats were investigated. Isoproterenol (100 mg/kg body weight) was administered to induce MI. The ST-segment, QT interval, and T wave were widened, and the QRS complex and P wave were shortened in the electrocardiogram (ECG) and the serum cardiac diagnostic markers and heart mitochondrial lipid peroxidation products, calcium ions, and reactive oxygen species (ROS) were elevated and the heart mitochondrial antioxidants, tricarboxylic acid cycle, and respiratory chain enzymes were lessened in isoproterenol-induced myocardial infarcted rats. The heart mitochondrial damage was noted in the transmission electron microscopic study. The whole heart weight was increased and the subunits of nicotinamide adenine dinucleotide phosphate – oxidase 2 (Nox 2) genes such as cybb and p22-phox and cardiac hypertrophy genes such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), β -myosin heavy chain (β-MHC), and actin alpha skeletal muscle-1(ACTA-1) were highly expressed in the rat's heart by reverse transcription-polymerase chain reaction study. The β-caryophyllene (20 mg/kg body weight) pre- and co-treatment orally, daily for 21 days reversed changes in ECG and lessened cardiac diagnostic markers, ROS, and whole heart weight and ameliorated mitochondrial damage and Nox/ANP/BNP/β-MHC/ACTA-1cardiac hypertrophy pathways in isoproterenol-induced myocardial infarcted rats. The observed effects might be due to the antioxidant, anti-mitochondrial damaging, and anti-cardiac hypertrophic mechanisms of β-caryophyllene.

Chemical chaperon 4-phenylbutric acid improves cardiac function following isoproterenol-induced myocardial infarction in rats.

4-Phenyl butyric acid (4-PBA) is a chaperone-mediated autophagy (CMA) inducer, which eliminates unnecessary and damaged cellular components through lysosomal enzymes. It could reduce misfolded and unfolded proteins produced after myocardial infarction (MI) and can improve cardiac function. We aimed to investigate the effect of 4-PBA on isoproterenol-induced MI in rats. Isoproterenol (100 mg/kg) was injected subcutaneously for two consecutive days simultaneous with an intraperitoneal (IP) injection of 4-PBA at 20, 40, or 80 mg/kg at 24-hr intervals for five days. On day 6, hemodynamic parameters, histopathological changes, peripheral neutrophil count, and total anti-oxidant capacity (TAC) were evaluated. The expression of autophagy proteins was measured by using western blotting. 4-PBA significantly improved post-MI changes in hemodynamic parameters. Histological improvement was found in 4-PBA 40 mg/kg (P<0.05). The neutrophil count in the peripheral blood significantly decreased in the treatment groups compared with isoproterenol. Furthermore, 4-PBA at 80 mg/kg significantly increased the serum TAC compared with isoproterenol (P<0.001). Western blotting showed a significant decrease in the P62 level (P<0.05) of 40 and 80 mg/kg 4-PBA treated groups. This study demonstrated that 4-PBA could have a cardio-protective effect against isoproterenol-induced MI, which can be due to autophagy modulation and oxidative stress inhibition. Obtaining effective results in different doses shows the need for an optimum degree of cell autophagic activity.

Combination of Empagliflozin and Liraglutide protects heart against isoproterenol-induced myocardial infarction in rats

Cardiovascular benefit of new anti-hyperglycemic agent such as glucagon like peptide-1 receptor agonist (GLP-1RA) or sodium glucose co-transporter-2 inhibitor (SGLT2i) has been proven, with the proposed-mechanism that might be complementary. We investigated the effects of its combination on blood glucose profile and cardiac biomarkers. The rats were given lipid emulsion for 2 weeks, followed by a single dose of streptozotocin (STZ) 35 mg/kg BW, then treated with empagliflozin and/ liraglutide for 30 days while receiving isoproterenol (ISO) 85 mg/kg on day 29 and 30. The results showed no superior improvement on fasting blood glucose (FBG) and insulin sensitivity (KITT) in the combination group compared to empagliflozin/liraglutide group. However, the combination group showed a higher inhibition in almost all biomarkers, specifically against the elevation of CK-MB compared to one of these agents alone. The histopathological examination using H&amp;E staining even showed a minimal inflammation and gap between cardiomyocytes. These findings may indicate the combination of empagliflozin and liraglutide has a better cardiac protection effect.

Evidence of the Cardioprotective Effects of Aloysia polystachya in Isoproterenol-Induced Myocardial Infarction in Rats

Aloysia polystachya is a plant species that is widely used in Brazilian folk medicine for the treatment of different disorders that affect the cardiovascular system. The aim of the study was to investigate the cardioprotective effects of an ethanol-soluble fraction of A. polystachya (ESAP) on isoproterenol-induced myocardial infarction in rats. Different groups of rats (n = 8) were orally treated with ESAP (30, 100, and 300 mg/kg), carvedilol (10 mg/kg), or vehicle (filtered water; 1 mL/100 g) for 7 days. Naive rats received no treatment. On the morning of day 6, acute myocardial infarction was induced by the acute oral administration of isoproterenol (100 mg/kg). On the morning of day 8, all rats underwent electrocardiography and transthoracic echocardiography. Blood samples were then collected, and serum levels of creatine kinase-MB fraction (CK-MB) and cardiac troponin T (cTNT) were quantified. ESAP significantly reduced electrocardiographic changes, improved the ventricular ejection fraction, and reduced serum levels of CK-MB and cTNT in infarcted rats. The cardioprotective effects of ESAP could be exploited as an effective tool against isoproterenol-induced myocardial infarction in rats.

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.

Cardioprotective Role of Scopoletin on Isoproterenol-Induced Myocardial Infarction in Rats.

Scopoletin is a phenolic coumarin isolated from a variety of plants and was originally used to treat various diseases including arthritis as well as bone-related diseases. The goal of this study was to determine scopoletin's therapeutic potential in an animal model of myocardial infarction induced with ISO. There were five groups of albino male rats. Group I (control) animals were orally treated with olive oil. Group II (scopoletin) animals were pre-treated orally with a 50-mg dosage of scopoletin for 28 days. Group III (ISO-treated) animals were treated with 85mg/kg of ISO subcutaneously for 2 consecutive days (29th and 30th day). Group IV (scopoletin and ISO) animals were pre-treated orally with 25mg of scopoletin for 28 days before exposure to ISO. Group V (scopoletin and ISO) animals were pre-treated with 50mg of scopoletin for 28 days before exposure to ISO. In the ISO-administered animals, a wider heart-to-body weight ratio, a higher heart weight, higher cardiac diagnostic markers, higher MDA levels and related antioxidant levels, inflammatory, and apoptotic markers were observed. Scopoletin pre-treatment with ISO (25 and 50mg/kg b.wt) significantly reduced heart-to-body weight ratio, cardiac diagnostic markers, MDA, inflammatory markers, and apoptotic markers. Meantime, a pre-treatment with scopoletin increased the levels of antioxidant enzymes. Inflammation and necrosis were observed in the histopathology of heart tissue of ISO-treated animals and these histopathological conditions were reversed by scopoletin pretreatment. The antioxidant and anti-inflammatory properties of ISO-treated rats were shown to be increased by scopoletin, showing its therapeutic potential against cardiovascular diseases. Through the use of its antioxidant and anti-inflammatory properties, scopoletin exhibited anti-myocardial infarction properties. However, further preclinical studies will be required to demonstrate the mechanism of action of scopoletin involved in anti-myocardial infarction.

Effects of exercise preconditioning on NLRP3 and mitochondrial fission in isoproterenol-induced myocardial infarcted rats

Effects of exercise preconditioning on NLRP3 and mitochondrial fission in isoproterenol-induced myocardial infarcted rats

Protective Effects of L-2-Oxothiazolidine-4-Carboxylate during Isoproterenol-Induced Myocardial Infarction in Rats: In Vivo Study.

This study aimed to evaluate the cardioprotective effects of L-2-oxothiazolidine-4-carboxylate (OTC) against isoproterenol (ISO)-induced acute myocardial infarction (MI) in rats. Results demonstrated that OTC treatments inhibited ISO-induced oxidative damage, suppressed lipid peroxidation, and increased superoxide dismutase and catalase activity in the hearts of the treated rats compared to those of the untreated controls. The ISO-related NF-κB activation was reduced due to the OTC treatment, and lower degrees of inflammatory cell infiltration and necrosis in the hearts were observed. In summary, OTC treatments exerted cardioprotective effects against MI in vivo, mainly due to enhancing cardiac antioxidant activity.

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.

β-caryophyllene modulates B-cell lymphoma gene-2 family genes and inhibits the intrinsic pathway of apoptosis in isoproterenol-induced myocardial infarcted rats; A molecular mechanism

Myocardial infarction (MI) is one of the top causes of morbidity and mortality in the world. Prevention/treatment of MI is of utmost importance. This study planned to appraise the molecular mechanisms of β-caryophyllene on the intrinsic pathway of cardiomyocyte apoptosis in isoproterenol-induced myocardial infarcted rats. Rats were induced MI by isoproterenol (100 mg/kg body weight). The serum cardiac diagnostic markers, heart lipid hydroperoxides, heart lysosomal thiobarbituric acid reactive substances, and serum/heart lysosomal enzymes were considerably (P < 0.05) augmented, while heart antioxidants, heart lysosomal β-glucuronidase and cathepsin-D were considerably (P < 0.05) lessened in isoproterenol-induced myocardial infarcted rats. A reverse transcription-polymerase chain reaction study revealed altered expressions of B-cell lymphoma gene-2, B-cell lymphoma – extra-large, B-cell lymphoma-2 associated-x, and B-cell lymphoma-2 associated death promoter genes. Further, transmission electron microscopic study depicted damaged heart lysosomal structure. Histological study revealed mononuclear cell infiltration and congested dilated blood capillaries in between affected cardiac muscle fibres. Further, 2,3,5-triphenyl tetrazolium chloride staining showed a larger myocardial infarct size. The β-caryophyllene (20 mg/kg body weight) pre-and co-treatment orally, daily, for 21 days considerably (P < 0.05) ameliorated all these altered biochemical, transmission electron microscopic, molecular and histological parameters evaluated in myocardial infarcted rats. Thus, β-caryophyllene inhibited oxidative stress and lysosomal leakage, preserved the heart, and heart lysosomal structure, and prevented the intrinsic pathway of apoptosis. Moreover, it reduced infarct size. The antioxidant effects of β-caryophyllene are the possible mechanism for the observed anti-oxidative stress, anti-lysosomal damage, anti-apoptotic, and myocardial infarct size limiting effects.

Thymoquinone regulates nitric oxide synthase enzymes and receptor-interacting serine-threonine kinases in isoproterenol-induced myocardial infarcted rats

This study aims to investigate the protective effects of thymoquinone (THQ) in isoproterenol (ISO)-induced myocardial infarction (MI) in rats.Thirty-two rats were divided into four equal groups. Control, THQ; Intragastric(ig) by dissolved 20 mg/kg in 500 μl olive oil at 24-h intervals for 7 days, ISO; On the 6th and 7th days of the experiment, it was dissolved in 1 ml distilled water, 100 mg/kg, subcutaneously(sb), THQ + ISO; THQ was given 20 mg/kg at 24-h intervals for 7 days, 100 mg/kg was given on days 6 and 7 of the ISO experiment. At the end of the experiment, blood and heart tissues were taken and histological, Western blot and biochemical analyzes were performed.In the ISO group, cardiomyocyte damage and large necrotic areas were observed. While neuronal nitric oxide synthase (nNOS) decreased, inducible NOS (iNOS) and endothelial NOS (eNOS) expression increased. Receptor-interacting serine-threonine kinase (RIP/RIPK) RIP1 and RIP3 protein levels were increased. Lactate dehydrogenase (LDH), creatin-kinase (CK-MB) and cardiac troponin I (cTn-I) levels were increased. Atrial natriuretic peptide (ANP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were decreased. THQ caused the reduction of necrotic areas caused by ISO. NOS regulated enzyme levels. Increased ISO-induced decreased RIP1 and RIP3 expressions. THQ regulated the biochemical parameter levels.ISO triggers MI-induced necrosis through NOS enzymes by causing severe histological changes in heart tissue. THQ, on the other hand, reveals that it can be an important antinecrotic agent in the prevention of MI-induced damage by regulating both NOS enzyme levels and necrosis markers.

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.