Serum Creatine kinase-MB Research Articles

18β-Glycyrrhetinic acid exerts cardioprotective effects against BPA-induced cardiotoxicity through antiapoptotic and antioxidant mechanisms.

Bisphenol A (BPA) is a synthetic environmental pollutant widely used in industry, as well as is an endocrine disrupting chemicals and has a toxic effects on heart tissue. The aim of this study is to reveal the cardioprotective effects of 18β-glycyrretinic acid (GA) against BPA-induced cardiotoxicity in rats. In this study, 40 male rats were used and five different groups (each group includes eight rats) were formed. The rats were applied BPA (250 mg/kg b.w.) alone or with GA (50 and 100 mg/kg b.w.) for 14 days. Rats were killed on Day 15 and heart tissues were taken for analysis. GA treatment decreased serum lactate dehydrogenase andcreatine kinase MB levels, reducing BPA-induced heart damage. GA treatment showed ameliorative effects against lipid peroxidation and oxidative stress caused by BPA by increasing the antioxidant enzyme activities (glutathione peroxidase, superoxide dismutase, and catalase) and GSH level of the heart tissue and decreasing the MDA level. In addition, GA showed antiapoptotic effect by increasing Bcl-2, procaspase-3, and -9 protein expression levels and decreasing Bax, cytochrome c, and P53 protein levels in heart tissue. As a result, it was found that GA has cardioprotective effects on heart tissue by exhibiting antioxidant and antiapoptotic effects against heart damage caused by BPA, an environmental pollutant. Thus, it was supported that GA could be a potential cardioprotective agent.

Role of Biomarkers of Myocardial Injury to Predict Adverse Outcomes in Hypertrophic Cardiomyopathy.

Serum troponins and CK-MB (creatine kinase-MB) are readily detectable and reliable cardiac-specific biomarkers of subclinical myocardial injury. This study explores the roles of cTnI (cardiac troponin I) and CK-MB in hypertrophic cardiomyopathy (HCM). This study included 1045 patients with HCM who had baseline cTnI and CK-MB measurements at Fuwai Hospital between 1999 and 2019. Patients were excluded if they had undergone percutaneous coronary intervention or coronary artery bypass grafting, or had renal failure. Five end points were studied: all-cause death, cardiovascular death, noncardiovascular death, sudden cardiac death, and other cardiovascular death. Cox regression was used to assess the associations of cTnI and CK-MB levels with outcomes. Nine hundred seventy patients with available follow-up data were finally analyzed (mean age, 49.3 years; 36.4% female). During the median 4.3-year follow-up period, 87 patients reached the end points. Higher cTnI (per 0.05 ng/mL increase) and CK-MB (per 1 IU/L increase) levels were associated with increased risks of all-cause death (cTnI: adjusted hazard ratio [HR], 1.038, P<0.001; CK-MB: adjusted HR, 1.021, P=0.004), cardiovascular death (cTnI: adjusted HR, 1.040, P<0.001; CK-MB: adjusted HR, 1.025, P=0.006), and sudden cardiac death (cTnI: adjusted HR, 1.045, P<0.001; CK-MB: adjusted HR, 1.032, P=0.001). Patients with elevated levels of both cTnI and CK-MB had worse prognoses than patients with an elevated level of either biomarker alone and patients who did not have an elevated level of either biomarker. Addition of the binary indicator elevation of both cTnI and CK-MB significantly improved the discrimination and reclassification abilities of the standard HCM Risk- sudden cardiac death model (C statistics: P=0.002; net reclassification improvement, 0.652; integrated discrimination improvement, 0.064). Comprehensive evaluations of biomarkers of myocardial injury, cTnI and CK-MB, have considerable value for predicting adverse outcomes among patients with HCM. Routine cTnI and CK-MB assessments may help to guide implantable cardioverter defibrillator implantation for primary prevention in HCM.

Effect and mechanism of Poria cocos polysaccharides on myocardial cell apoptosis in rats with myocardial ischemia-reperfusion injury by regulating Rho-ROCK signaling pathway

This study aimed to investigate the effect and underlying mechanism of Poria cocos polysaccharides(PCP) on myocardial cell apoptosis in the rat model of myocardial ischemia-reperfusion injury(MI/RI). Male SPF-grade SD rats were randomly divided into a sham group(saline), a model group(saline), low-and high-dose PCP groups(100 and 200 mg·kg~(-1)), and a fasudil group(10 mg·kg~(-1)), with 16 rats in each group. Except for the sham group, the other four groups underwent left anterior descending coronary artery ligation for 30 min followed by reperfusion for 2 h to establish the MI/RI model. The myocardial infarct area was assessed by TTC staining. Histological changes were observed through HE staining. Myocardial cell apoptosis was evaluated using TUNEL staining. Serum lactate dehydrogenase(LDH), creatine kinase MB(CK-MB), interleukin-1β(IL-1β) and IL-18 levels, myocardial superoxide dismutase(SOD) activity and malondialdehyde(MDA) levels were detected by ELISA. Protein expression of B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), cleaved caspase-3, Ras homolog gene A(RhoA), myosin phosphatase target subunit 1(MYPT-1), phosphorylated MYPT-1(p-MYPT-1), and Rho-associated coiled-coil forming kinase 1(ROCK 1) were measured by Western blot. Pathological staining of myocardial tissue revealed that in the model group, there was focal necrosis of myocardial tissue, myocardial cell swelling, unclear boundaries, and neutrophil infiltration. These pathological changes were alleviated in the low-and high-dose PCP groups and the fasudil group. Compared with the model group, the low-and high-dose PCP groups and the fasudil group showed significantly reduced myocardial infarct area and myocardial cell apoptosis rate. Compared with the sham group, the model group exhibited elevated serum LDH, CK-MB, IL-1β and IL-18 levels, increased MDA levels, relative protein expression of Bax, cleaved caspase-3, RhoA, ROCK1 and p-MYPT-1, and decreased myocardial SOD levels and Bcl-2 protein expression. Compared with the model group, the PCP groups and the fasudil group showed lowered serum LDH, CK-MB, IL-1β and IL-18 levels, decreased MDA levels, relative protein expression of Bax, cleaved caspase-3, RhoA, ROCK1 and p-MYPT-1, and increased myocardial SOD levels and Bcl-2 protein expression. PCP exhibited a certain preventive effect on myocardial tissue pathological damage and myocardial cell apoptosis in MI/RI rats, possibly related to the inhibition of the Rho-ROCK signaling pathway activation, thereby reducing oxidative stress and inflammatory responses.

Alkaloid-rich extract of Lannea egregia leaf protect against cardiomyopathy in streptozotocin-induced type 2 diabetic rats

BackgroundLannea egregia leaf has been used locally for the management of diseases with limited scientific support. Hence, the cardiomyopathy protective ability of an alkaloid-rich extract of L. egregia leaf in streptozotocin-induced type 2 diabetic rats was investigated in this study. A L. egregia leaf alkaloid-rich extract was obtained using a standard procedure. Streptozotocin was injected into the experimental animals intraperitoneal at a dose of 45 mg/kg body weight to induce type 2 diabetes mellitus, prior to this, the animals were given 20 % (w/v) fructose for one week. Thus, the animals were grouped into five (n = 8), comprising normal control (NC), diabetic control (DC), diabetic rats treated with low (50 mg/kg body weight) and high (100 mg/kg body weight) doses of L. egregia alkaloid-rich leaf extracts (i.e., LEL and LEH, respectively), and 200 mg/kg body weight metformin (MET). The animals were sacrificed on the 21st day, and blood and hearts were harvested and used for the determination of serum lipid profiles, atherogenic indices, oxidative stress biomarkers, ATPase activities, cardiac enzyme activities, creatinine kinase-MB, cardiac troponin, cytokines, N-terminal pro-B-type brain natriuretic peptide (NT-pro BNP) and histology examination. ResultsThe results revealed that diabetic rats treated with LEL, LEH, and MET significantly (p < 0.05) reduced their fasting blood glucose levels, improved their serum lipid profile, and decreased their cardio-risk ratio, atherogenic index of plasma, atherogenic coefficient, and atherosclerosis index. In addition, diabetic treated with on LEL, LEH, and MET significantly (p < 0.05) ameliorated oxidative stress biomarkers, increased selected ATPase activities, increased specific cardiac enzyme activities, and decreased serum creatine kinase-MB, serum cardiac troponin I and T, as well as cytokines and NT-pro BNP in diabetic rats. These were supported by the histology examination by improving myocardial degeneration in diabetic rats administered LEL, LEH, and MET. ConclusionHence, it can be presumed that alkaloid-rich extracts obtained from L. egregia leaves could be beneficial in ameliorating diabetic cardiomyopathy conditions.

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.

Study of Demographic Profile, Clinical Manifestations, and a Short-term Follow-up of Young Patients Presenting with Myocardial Infarction at a Tertiary Care Hospital

Background: The present study was undertaken to analyze the clinical manifestations, treatment, and outcome of young patients presenting with myocardial infarction (MI) at a tertiary care hospital. Materials and Methods: The present study was a cross-sectional, observational hospital-based study conducted on patients with MI younger than 40 years. Results: Among the 50 patients, there were 49 males and one female. The age group ranged from 25 to 40 years—most of the patients presented with typical chest pain. Dyslipidemia was the most common risk factor 64%, followed by hypertension 42%, smoking 30%, high altitude area (HAA) 18%, positive family history 12%, metabolic syndrome 06%, and chronic kidney disease 02%. Serial creatine kinase-MB was elevated in 33 (66%) patients and normal in 17 (34%) patients. Troponin T/I was positive in 41 (82%) patients and negative in 09 (18%) patients. On echocardiogram, almost all patients had regional wall motion abnormality. The left ventricular ejection fraction &lt;30% (2%), 30%–40% (18%), 41%–50% (32%), and &gt;50% (22%). All 50 patients underwent a coronary angiogram, 19 had small vessel disease (38%), and 30 had recanalized/slow flow noted in coronaries (60%). Most of the patients, 36 (72%), underwent thrombolysis and had evidence of recanalized coronaries on coronary angiography; one patient was taken up for primary angioplasty in MI, 14 patients underwent percutaneous transluminal coronary angioplasty with stenting. Conclusion: The study describes the clinic-demographic profile of MI in young. The role of dyslipidemia, hypertension, smoking, high altitude area, and positive family history may need further elucidation in these patients.

Dexmedetomidine Pretreatment Protects Against Myocardial Ischemia/Reperfusion Injury by Activating STAT3 Signaling.

Myocardial infarction is a common perioperative complication, and blood flow restoration causes ischemia/reperfusion injury (IRI). Dexmedetomidine (DEX) pretreatment can protect against cardiac IRI, but the mechanism is still insufficiently understood. In vivo, myocardial ischemia/reperfusion (30 minutes/120 minutes) was induced via ligation and then reperfusion of the left anterior descending coronary artery (LAD) in mice. Intravenous infusion of 10 μg/kg DEX was performed 20 minutes before ligation. Moreover, the α2-adrenoreceptor antagonist Yohimbine and STAT3 inhibitor Stattic were applied 30 minutes ahead of DEX infusion. In vitro, hypoxia/reoxygenation (H/R) with DEX pretreatment for 1 hour was performed in isolated neonatal rat cardiomyocytes. In addition, Stattic was applied before DEX pretreatment. In the mouse cardiac ischemia/reperfusion model, DEX pretreatment lowered the serum creatine kinase-MB isoenzyme (CK-MB) levels (2.47 ± 0.165 vs 1.55 ± 0.183; P < .0001), downregulated the inflammatory response ( P ≤ .0303), decreased 4-hydroxynonenal (4-HNE) production and cell apoptosis ( P = .0074), and promoted the phosphorylation of STAT3 (4.94 ± 0.690 vs 6.68 ± 0.710, P = .0001), which could be blunted by Yohimbine and Stattic. The bioinformatic analysis of differentially expressed mRNAs further confirmed that STAT3 signaling might be involved in the cardioprotection of DEX. Upon H/R treatment in isolated neonatal rat cardiomyocytes, 5 μM DEX pretreatment improved cell viability ( P = .0005), inhibited reactive oxygen species (ROS) production and calcium overload (both P ≤ .0040), decreased cell apoptosis ( P = .0470), and promoted STAT3 phosphorylation at Tyr705 (0.102 ± 0.0224 vs 0.297 ± 0.0937; P < .0001) and Ser727 (0.586 ± 0.177 vs 0.886 ± 0.0546; P = .0157), which could be abolished by Stattic. DEX pretreatment protects against myocardial IRI, presumably by promoting STAT3 phosphorylation via the α2-adrenoreceptor in vivo and in vitro.

Effects of heat shock protein 90 on complement activation in myocardial ischemia/reperfusion injury after pioglitazone preconditioning.

Heat shock protein 90 (HSP90) appears to have a pivotal function in ischemic preconditioning. Pioglitazone preconditioning (PioC) attenuates myocardial ischemia/reperfusion (I/R) injuries. The current study aims to investigate the role of HSP90, complement C3 and C5a, and nuclear factor kappa-B (NF-κB) in PioC-induced cardioprotection. A total of 80 rats were randomly categorized into 4 groups, as follows: sham, I/R, PioC, and PioC+HSP90 inhibitor geldanamycin (PioC+GA). The sham group rats had a thoracotomy, in which the ligature was passed by the heart with no ligation (150 min). The other 3 groups were exposed to ischemia (30 min) followed by reperfusion (2 h). In the PioC group, pioglitazone (3 mg/kg) was administered intravenously 24 h before ischemia. In the PioC+GA group, after being pretreated with pioglitazone, GA was administered (intraperitoneally, 1 mg/kg) 30 min before ischemia. Myocardial infarct sizes (ISs), apoptosis rates, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin I (cTnI) serum levels were determined. The HSP90, C3, NF-κB, C5a, B-cell lymphoma-2 (Bcl-2), and Bax expression levels, as well as interleukin (IL)-1β, IL-6, intercellular cell adhesion molecule-1 (ICAM-1), and tumor necrosis factor alpha (TNF-α) mRNA levels were measured. The myocardial ISs, serum CK-MB, cTnI and LDH levels, apoptosis rates, IL-1β, IL-6, TNF-α, ICAM-1 release, as well as Bax, C5a, C3, and NF-κB protein expression were considerably lower in the PioC group than in the I/R group (p < 0.05). The Bcl-2 and HSP90 expression was higher in the PioC group than in the I/R group (p < 0.05). Geldanamycin inhibited the effects of PioC. These data strongly demonstrate that the PioC-induced is dependent upon HSP90 activity. The HSP90 is indispensable for PioC-mediated cardioprotection. The HSP90 attenuates I/R-induced ISs, apoptosis of cardiomyocytes and myocardial inflammation through C3, C5a and NF-κB activation inhibition.

The myokine decorin improves the cardiac function in a rat model of isoprenaline-induced myocardial infarction.

Myocardial infarction is a common cause of disability. Decorin is a myokine that has anti-inflammatory, anti-apoptotic effects. Some studies stated that decorin protects myocardium from ischemia. Other studies stated that decorin levels are associated with acute coronary syndrome. The study aimed to investigate the therapeutic role of decorin on cardiac function in a rat model of myocardial infarction. Thirty adult male Wistar rats were divided into control group-rats were subcutaneously injected with normal saline, isoprenaline-injected group-rats were subcutaneously injected with isoprenaline (85 mg/kg) once daily for 2 days to induce myocardial infarction, and decorin ± isoprenaline-injected group-rats were injected as the previous group, followed by decorin injection (0.1 mg/kg) once daily for 7 days. Cardiac hemodynamics, serum lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), oxidative stress markers, gene expression for myocardial-transforming growth factor beta 1 (TGF-β1), interleukin 1 b (IL-1β), tumor necrosis factor alpha (TNF-α), and cardiac caspase-3 immunohistochemical analysis were done. Isoprenaline + decorin group had significant improvement in cardiac hemodynamics and oxidative stress markers; significant decrease in serum CK-MB, LDH, and myocardial gene expression for TNF-α, IL-1β, and TGF-β1; and decreased cardiac caspase-3 immunoreactivity was present. Therefore, decorin can be used as a therapeutic agent after myocardial infarction as it improved the cardiac function.

Potential cardioprotective and anticancer effects of carvedilol either free or as loaded nanoparticles with or without doxorubicin in solid Ehrlich carcinoma-bearing mice

AimThe aim of this study was to investigate the potential cardioprotective and anti-cancer effects of carvedilol (CAR) either free or as loaded nano-formulated with or without doxorubicin (DOX) in solid Ehrlich carcinoma (SEC)-bearing mice. It focused on assessment of cardiac damage, drug resistance, apoptosis, oxidative stress status, angiogenesis and proliferation. MethodsCAR was loaded into poly-D,L lactic-co-glycolic acid)PLGA(or Niosomes. SEC was induced in female albino mice as an experimental model of breast cancer. Seventy-two mice were randomly divided into 9 equal groups (Normal control, Untreated-SEC, SEC + DOX, SEC + CAR-free, SEC + CAR-PLGA, SEC + CAR-Niosomes, SEC + DOX + CAR-free, SEC + DOX + CAR-PLGA and SEC + DOX + CAR-Niosomes). Tumor volume and survival rate were recorded. On day 28 from tumor inoculation, mice were sacrificed, and blood samples were collected for determination of serum lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB). One part from tumor tissues was prepared for assessment of multidrug resistance protein-1 (MDR-1), caspase-3, reduced glutathione (GSH) and malondialdehyde (MDA), while the other part was processed for histopathological examination and immunohistochemical expression of vascular endothelial growth factor (VEGF) and Ki-67. ResultsThere was non-significant difference between CAR-free, CAR-PLGA and CAR-Niosomes as anticancer either alone or when combined with DOX. However, CAR-free demonstrated potential cardioprotective effects against cardiac damage mediated by cancer or DOX that have been enhanced using CAR-PLGA or CAR-Niosomes, but that of Niosomes outperformed them both. ConclusionCAR could be used as an adjuvant therapy with DOX, especially when nanoformualted with PLGA and even better with Niosomes, without compromising its cytotoxicity against cancer cells and preventing its cardiotoxic impacts.

NSC228155 alleviates septic cardiomyopathy via protecting mitochondria and inhibiting inflammation

Septic cardiomyopathy is a lethal symptom of sepsis. Discovery of effective therapy that prevents cardiac injury in sepsis is critical in the clinical management of sepsis. NSC228155 is a novel compound with therapeutic potential on acute kidney injury by preventing apoptosis and protecting mitochondria. Whether NSC228155 protects against septic cardiomyopathy is unclear. In the present study, adult C57BL/6J mice were i.p injected with 5 mg/kg/day NSC228155 for 2 days before 10 mg/kg lipopolysaccharide (LPS) injection. Cardiac functional testing and sampling for serum and tissue were performed 12 and 24 h post LPS injection, respectively. NSC228155 significantly improved cardiac function examined by echocardiography, decreased the serum lactate dehydrogenase (LDH) and creatine kinase-MB, and pathologically alleviated cardiac injury in LPS mice. Accordingly, NSC228155 attenuated cardiomyocytes’ mitochondrial damage as shown by decreased damaged mitochondrial ratio and activated signals for mitochondrial biogenesis, dynamics and mitophagy in LPS mice model. Metabolomics analysis demonstrated that NSC228155 corrected the metabolic disturbance involved in oxidative stress and energy metabolism, and decreased tissue injury metabolites in LPS-stimulated cardiac tissue. In the LPS-stimulated cardiac cell culture derived from human induced pluripotent stem cells, NSC228155 effectively restored the beating frequency, decreased LDH release, and protected mitochondria. NSC228155 also inhibited inflammation shown by decreased pro-inflammatory mediators in both serum and cardiac tissue in LPS model. Taken together, NSC228155 significantly improved cardiac function by directly preventing against cardiac cell injury and inhibiting inflammation in LPS model, hence may be a potential novel therapy against septic cardiomyopathy.

Hemodynamic impairment induced by Crotoxin using in vivo and ex vivo approach in a rat model

Crotalus durissus snakebite represent 10 % of snakebite cases in Brazil, which cardiovascular disorders are associated with severe cases. Considering crotoxin (CTX) as the major venom component, the present study aimed to evaluate the hemodynamic alterations induced by CTX using in vivo and ex vivo approaches in a rat model. In vivo cardiac function parameters were analyzed from anesthetized rats treated with CTX or saline only (Sham), along with serum creatine kinase MB (CK-MB) and lung myeloperoxidase. From the same animals, hearts were isolated and functional parameters evaluated in Langendorff method ex vivo. CTX binding to myoblast cell line in vitro were evaluated using confocal microscopy and flow cytometry. CTX was capable of reducing arterial and diastolic blood pressure, heart rate, along with left ventricle pressure development or decay during systole (LVdP/dtmax and LVdP/dtmin) in vivo, however no differences were found in the ex vivo approach, showing that intrinsic heart function was preserved. In vitro, CTX binding to myoblast cell line was mitigated by hexamethonium, a nicotinic acetylcholine receptor antagonist. The present study has shown that CTX induce hemodynamic failure in rats, which can help improve the clinical management of cardiovascular alterations during Crotalus durissus snakebite.

Exploring the cardioprotective effects of canagliflozin against cisplatin-induced cardiotoxicity: Role of iNOS/NF-κB, Nrf2, and Bax/cytochrome C/Bcl-2 signals.

Cardiotoxicity is a severe considerable side effect of cisplatin (CDDP) that requires much medical attention. The current study investigates the cardioprotective effects of canagliflozin (CA) against CDDP-induced heart toxicity. Rats were allocated to the control group; the CA group was administered CA 10 mg/kg/day orally for 10 days; the CDDP group was injected with 7 mg/kg, intraperitoneal as a single dose on the 5th day, and the CDDP + CA group. Compared to the CDDP-treated group, CA effectively attenuated CDDP-induced heart injury as evidenced by a decrease of serum aspartate aminotransferase,alkaline phosphatase, creatine kinase-MB, and lactate dehydrogenase enzymes and supported by the alleviation of histopathological changes in cardiac tissues. Biochemically, CA attenuated cardiac oxidative injury through upregulation of the nuclear factor-erythroid 2 related factor 2 (Nrf2) signal. CA suppressed inflammation by decreasing cardiac NO2 - , MPO, iNOS, nuclear factor kappa B(NF-κB),tumor necrosis factor-alpha, and interleukin 1-beta levels. Besides, CA significantly upregulated cardiac levels of phosphoinositide 3-kinase(PI3K), protein kinase B(AKT), and p-AKT proteins. Moreover, CA remarkably mitigated CDDP-induced apoptosis via modulation of Bax, cytochrome C, and Bcl-2 protein levels. Together, the present study revealed that CA could be a good candidate for preventing CDDP-induced cardiac injury by modulating iNOS/NF-κB, Nrf2, PI3K/AKT, and Bax/cytochrome C/Bcl-2 signals.

Jia-Wei-Si-Miao-Yong-An decoction modulates intestinal flora and metabolites in acute coronary syndrome model.

We assessed the efficacy of the traditional Chinese medicine formulation Jia-Wei-Si-Miao-Yong-An decoction (HJ11) in the treatment of acute coronary syndrome and evaluated its impact on the intestinal microbiota and their metabolites. An acute coronary syndrome model was established in rats, which were randomly assigned to the model, HJ11 treatment, and atorvastatin treatment groups. Rats were then administered saline solution (model and sham operation control groups) or drugs by oral gavage for 28 d. Echocardiography was performed and serum creatine kinase-MB and cardiac troponin I levels were monitored to examine the cardiac function. Inflammation was evaluated using hematoxylin and eosin staining of heart tissue, and serum interleukin-2, interleukin-6, tumor necrosis factor alpha, and high-sensitivity C-reactive protein measurements. Gut microbiota composition was analyzed via 16S rRNA gene sequencing. Metabolomics was used to determine fecal metabolites and elucidate the modes of action of HJ11 in acute coronary syndrome treatment. HJ11 improved cardiac function and attenuated inflammation in rats with acute coronary syndrome. Relative to the untreated model group, the HJ11-treated group presented normalized Firmicutes/Bacteroidetes ratio and reduced abundances of the bacterial genera norank_f__Ruminococcaceae, Desulfovibrio, Clostridium_sensu_stricto_1, Adlercreutzia, Staphylococcus, Bacteroides, Prevotella, Rikenellaceae_RC9_gut_group, unclassified_o__Bacteroidales, and Ruminococcus_gauvreauii_group. We found 23 differentially expressed intestinal metabolites, and the enriched metabolic pathways were mainly related to amino acid metabolism. We also discovered that asymmetric dimethylarginine levels were strongly associated with cardiovascular disease. Correlation analyses revealed strong associations among intestinal microflora, their metabolites, proinflammatory factors, and cardiac function. Hence, the therapeutic effects of HJ11 on acute coronary syndrome are related to specific alterations in gut microbiota and their metabolites. This work demonstrated that HJ11 effectively treats acute coronary syndrome. HJ11 seems to increase the abundance of beneficial bacterial taxa (Bacteroides and Rikenellaceae_RC9_gut_group), mitigate the risk factors associated with cardiovascular disease, alter bacterial metabolites, lower asymmetric dimethylarginine levels, and effectively treat acute coronary syndrome.

Effect of Panchakarma therapy in the management of congenital muscular dystrophy

Congenital Muscular Dystrophy (CMD) is a general term for a group of genetic muscle disorder that occurs at birth (congenital) or early infancy. Muscular dystrophies are characterized by weakness and degeneration of various voluntary muscles of the body. The severity, specific symptoms, and progression of these disorders vary greatly. A six and half-year-old female child was brought by her parents to the outpatient department (OPD) of Kaumarabhritya department, with the chief complaints of toe walking, unable to balance her body, tremors while standing, unable to stand from a sitting position without support, and unable to lift up both legs from the supine position. The patient visited the OPD with a diagnosis as CMD. After examination, internal medications: Bilwadi gutika, Ashwagandha churna, Pippali churna, Pravala bhasma, and Shirisharishta were prescribed along with Panchakarma procedures (~five therapeutic procedures) including Udwartana (~therapeutic massage using powders), Sarvanga abhyanga (~whole body oil massage), Swedana (~sudation therapy), Niruha basti (~therapeutic decoction enema), and Anuvasana basti (~therapeutic unctuous enema). After treatment, improvement in muscle power was seen. The total score of the Barthel index before the study was 70 and after the study was 95, which shows improvement in activity of daily life. Serum creatine phosphokinase and serum creatine kinase-MB values were insignificantly improved before and after treatment. Liver function test, kidney function test, and electrocardiogram before and after treatment were within normal limits, this shows the safety of the internal medication and Ayurvedic Panchakarma procedures. Improvement in the activity of daily life and muscle power seen in the present case gives hope, where there are still no satisfactory management options for patients with CMD are available.

Body fat percentage and infarct size in patients with non-ST segment elevation myocardial infarction.

Obesity is a global health problem that increases the risk of coronary artery disease (CAD). However in studies, it has been observed that when the disease develops, obese patients have a more favorable prognosis than leaner patients. This is called the "obesity paradox." This study aims to evaluate the effect of obesity assessed with body fat percentage (BFP) and relative fat mass (RFM) besides body mass index (BMI) on infarct size (IS) estimated from peak creatine kinase-MB (CK-MB) levels in patients with non-ST-segment elevation myocardial infarction (NSTEMI). Patients with a diagnosis of NSTEMI who underwent coronary angiography between January 2017 and January 2022 were retrospectively evaluated. Patients without available anthropometric data to calculate BMI, BFP, and RFM and serial CK-MB measurements were excluded from the study. BMI was calculated using weight(kg)/(height[m])2 formula. Patients were dichotomized as obese (BMI≥30 kg/m2) and non-obese (BMI<30 kg/m2) to compare baseline characteristics. BFP and RFM were calculated from anthropometric data. Linear regression analysis was performed to define predictors of IS. Final study population consisted of 748 NSTEMI patients (mean age was 59.3±11.2 years, 76.3% were men, 36.1% of the patients were obese). Obese patients were more likely to be female, hypertensive, and diabetic. Smoking was less frequently observed in obese patients. Peak CK-MB levels were similar among groups. Obese patients had higher in-hospital left ventricular ejection fraction, and less severe CAD was observed in coronary angiographies of these patients. Multivariable regression analysis identified diabetes mellitus, systolic blood pressure, white blood cell count, hemoglobin, and BFP (β=-4.8, 95% CI=-8.7; -0.3, p=0.03) as independent predictors of IS. Higher BFP is associated with smaller IS in NSTEMI patients. These findings support the obesity paradox in this patient group, but further, randomized controlled studies are required.

Protective effects ofLacticaseibacillus rhamnosuson isoprenaline-induced myocardial infarction in rats

Myocardial infarction (MI) is among the main public health problems in the world. This atherosclerotic cardiovascular disease (ASCVD), which seriously endangers human health, progresses to cause heart failure and myocardial fibrosis with a poor prognosis. The gut microbiota plays an important role in health and disease, including obesity and ASCVD. In this study, the protective effect of Lacticaseibacillus rhamnosus GG, known for its anti-inflammatory and antioxidant effects, on isoprenaline (ISO)-induced MI in rats was investigated. Rats were divided into four groups of seven rats in each group as control, ISO, L. rhamnosus, and ISO+L. rhamnosus.The ISO application was made by subcutaneous injection to the rats on the last two days (days 27th and 28th) of the 28-day substance administration. The rats were anesthetized 24 hours after the application of ISO, and blood samples were collected after electrocardiogram (ECG) recordings. To determine myocardial damage and protective effects of L. rhamnosus, serum creatine kinase-MB, cardiac troponin-I, tumor necrosis factor-alpha, interleukin-10, and C-reactive protein (CRP) levels were examined. In addition, ECG recordings were evaluated. While L. rhamnosus had a decreasing effect on cardiac troponin-I, creatine kinase-MB, CRP, and tumor necrosis factor-alpha levels, which increased due to ISO, it had an increasing effect on interleukin-10 levels. Similarly, it decreased the ST-segment elevation caused by ISO while increasing the reduced R wave amplitude.

Cardioprotective effects of minocycline against doxorubicin-induced cardiotoxicity

BackgroundDoxorubicin (Dox)-induced cardiotoxicity has limited its use. Inflammation, oxidative stress, and apoptosis have important roles in Dox-induced cardiotoxicity. Minocycline (Min) is an antibiotic with anti-inflammatory, anti-oxidant and anti-apoptotic properties. Here, the cardioprotective effects of Min against Dox-induced cardiotoxicity in adult male rats were evaluated. MethodsForty-two adult male rats were divided into six groups including control group (normal saline), Dox group, Min groups (Min 45 mg/kg and Min 90 mg/kg), and treatment groups (Dox + Min 45 mg/kg and Dox + Min 90 mg/kg). Dox (2.5 mg/kg) was administered three times a week for two weeks, and Min once a day for three weeks via intraperitoneal route. Cardiac tissue sections were stained with hematoxylin and eosin for histological examination. The activities of lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB) in serum as well as the activity of catalase and superoxide dismutase (SOD) in cardiac tissue were measured. Cardiac tissue levels of malondialdehyde (MDA), TNF-α, and IL-1β were also measured using ELISA. ResultsCompared with the Dox group, treatment with Min significantly decreased the activity of LDH and CK-MB. Min also increased the activity of catalase and SOD in the tissue samples. The results showed that the levels of MDA, TNF-α, and IL-1β in cardiac tissue samples were significantly lower in the Min groups compared with the Dox group. In addition, histopathological results showed that Min reduced the tissue damage caused by Dox. ConclusionMin reduced Dox-induced cardiotoxicity. The anti-oxidant and anti-inflammatory properties of Min may contribute to its protective effects.

Diallyl trisulfide modulated autophagy in isoproterenol induced acute myocardial infarction

BackgroundAcute myocardial infarction (AMI) is the most serious manifestation of coronary artery disease. The initial ischemia in AMI causes biochemical and metabolic alterations in cardiomyocytes.ObjectivesThe present study aimed to investigate the biomolecular mechanisms underlying cardioprotective effects of diallyl trisulfide (DATS) as well as captopril (CAP) in isoproterenol (ISO) induced AMI focusing on autophagy & PI3K/Akt signaling.MethodsSeventy male Albino rats were divided into seven groups as follows: Normal control, ISO, ISO + LY294002 (PI3K inhibitor), DATS+ISO, CAP+ISO, DATS+LY294002 + ISO, and CAP+LY294002 + ISO. All treatments (40 mg/kg DATS, 50 mg/kg CAP & 0.3 mg/kg LY294002) were given daily for two weeks before ISO injection (85 mg/kg for 2 days). At the end of the experiment, serum and cardiac tissues were collected. Serum cardiac troponin I (cTnI), and creatine kinase MB (CK-MB) were measured. Cardiac glutathione peroxidase (GSH-px), malondialdehyde (MDA), hypoxia-inducible factor 1 alpha (HIF-1α), autophagy proteins (P62 & LC3IIB) and gene expression of PI3K, Akt, FOXO-1, and eNOS were assessed. Histopathological examination of heart tissue was performed.ResultsDATS and CAP significantly (p < 0.01) decreased serum CK-MB and cTnI, cardiac levels of MDA, HIF-1α, p62 and LC3IIB along with an increase in GSH-px activity compared with ISO group. Moreover, DATS and CAP significantly up-regulated PI3K, Akt, and eNOS gene expression but down-regulated FOXO-1 expression compared to ISO group. However, LY294002 reversed DATS and CAP cardioprotective effects.ConclusionDATS and CAP prior treatment proved cardioprotective effects via modulation of autophagy, PI3K/Akt signaling, eNOS and FOXO-1 downregulation in ISO induced AMI rat model.

Curdione Relieved Isoproterenol-Induced Myocardial Damage through Inhibiting Oxidative Stress and Apoptosis.

Isoproterenol (ISO) is widely used to treat bronchial asthma, cardiogenic or septic shock, complete atrioventricular block, and cardiac arrest. However, it can also cause myocardial damage owing to infarct-like necrosis. Curdione, an extract of the Chinese herb Rhizoma Curcumae, has a variety of pharmacological activities, including cardioprotective effects. In this study, we investigated the protective effects of curdione and its underlying mechanisms in an ISO-induced myocardial injury model. Our results showed that curdione attenuated ISO-induced H9c2 cell proliferation inhibition and lactic dehydrogenase (LDH) release. Curdione ameliorated morphological damage and reduced the ISO-induced elevation of serum creatine kinase-MB isoenzyme (CK-MB) and LDH.Furthermore, curdione inhibited ISO-induced cell apoptosis, modulated the expression of Bcl-2 and Bax proteins, repealed the accumulation of ISO-induced reactive oxygen species (ROS), prevented mitochondrial dysfunction, and activated the Nrf2/SOD1/HO-1 signaling pathway. The above results show that curdione exerts a protective effect against ISO-induced myocardial damage by inhibiting apoptosis and oxidative stress, suggesting that curdione is a potential therapeutic strategy to prevent ISO-induced myocardial damage.