Serum Creatine kinase-MB Research Articles

Synbiotic supplementation ameliorates anxiety and myocardial ischaemia-reperfusion injury in hyperglycaemic rats by modulating gut microbiota.

Hyperglycaemia, hyperlipidaemia, hypertension and obesity are the main risk factors affecting the development and prognosis of ischaemic heart disease, which is still an important cause of death today. In our study, male Sprague-Dawley rats were fed either a standard diet (SD) or a high fat and high carbohydrate diet (HF-HCD) for 8weeks and streptozotocin (STZ) was injected at the seventh week of the feeding period. In one set of rats, a mixture of a prebiotic and probiotics (synbiotic, SYN) was administered by gavage starting from the beginning of the feeding period. Experimental myocardial ischaemia-reperfusion (30min/60min) was induced at the end of 8weeks. Hyperglycaemia, hypertension and increased serum low-density lipoprotein levels occurred in SD- and HF-HCD-fed and STZ-treated rats followed for 8weeks. Increased density of the Proteobacteria phylum was observed in rats with increased blood glucose levels, indicating intestinal dysbiosis. The severity of cardiac damage was highest in the dysbiotic HF-HCD-fed hyperglycaemic rats, which was evident with increased serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), tumour necrosis factor-α, and interleukin-6 levels, along with a decrease in ST-segment resolution index. SYN supplementation to either a normal or a high-fat high-carbohydrate diet improved gut dysbiosis, reduced anxiety, decreased CK-MB and cTnI levels, and alleviated myocardial ischaemia-reperfusion injury in hyperglycaemic rats.

Molecular insight of miRNA-217 role in the pathogenesis of myocardial infarction: Promising diagnostic biomarker and therapeutic target

BackgroundGlobally, myocardial infarction (MI) is one of the main causes of death. This study aims to investigate the role of miR-217 in the pathogenesis through targeting MAPK and PI3K/AKT signaling pathways in experimental model of myocardial infarction and studying the possible cardioprotective role of dihydromyricetin (DHM) through modulation of this pathway. MethodsDihydromyricetin was injected (100 mg/kg; p.o.) in isoprenaline induced myocardial infarction rat model for 14 days. Rats were anaesthetized and blood samples were taken for serum separation, estimation of creatine kinase-MB (CK-MB), and troponin-I levels after 24 h had passed since the last isoprenaline injection. In addition, the hearts were also used for the other biochemical studies and the histological evaluation. ResultsDHM resulted in a significant suppression of the elevated levels miR-217 and MAPK compared to the MI control group and restored the normal level of serum CK-MB. Furthermore, DHM successfully restored the oxidative balance and halted the pro-inflammatory mediators in the cardiac tissue. ConclusionAccordingly, our experiment emphasizes the anti-ischemic property that has been demonstrated through modulation of expression level of miR-217 and consequent deactivation of MAPK and PI3K/AKT signaling pathways, and this was assured by halting downstream pro-inflammatory markers.

Shikonin mitigates cyclophosphamide-induced cardiotoxicity in mice: the role of sirtuin-1, NLRP3 inflammasome, autophagy, and apoptosis.

The aim of this study was to elucidate the protective potential of shikonin (SHK) on cyclophosphamide (CP)-induced cardiotoxicity in Swiss albino mice. Mice received SHK in three different doses by oral gavage daily for 14 days and CP at 100mg/kg, intraperitoneally once on the seventh day. On the 15th day, mice were euthanized, blood collected, and hearts were removed to estimate various biochemical and histopathological parameters. CP significantly increased serum lactate dehydrogenase, creatine kinase-MB, troponin I and NT pro-BNP, and cardiac malondialdehyde and decreased cardiac total antioxidant capacity and Nrf2, whereas increased inflammatory markers in the cardiac tissues. CP also caused hypertrophy and fibrosis in the cardiac tissues via activation of IL6/JAK2/STAT3 while depressed SIRT1 and PI3K/p-Akt pathway with consequent increased apoptosis and dysregulation of autophagy. SHK treatment reversed these changes in a dose-dependent manner and showed a significant protective effect against CP-induced cardiotoxicity via suppressing oxidative stress, inflammation, and apoptosis with modulation of autophagy via induction of SIRT1/PI3K/p-Akt signaling. Shikonin may be used as an adjuvant to cyclophosphamide in cancer treatment, but further research is needed to investigate its effects on cardiotoxicity in distinct animal cancer models.

Significance of detecting cardiac troponin I and creatine kinase MB in critically Ill children without primary cardiac illness.

To investigate the incidence of myocardial injury in children with critically ill children without primary cardiac disease and the association between elevated cardiac troponin I (cTnl) and creatine kinase MB (CK-MB) concentrations and disease progression and prognosis to guide early treatment. The serum cTnI and CK-MB concentrations of 292 children with critically ill children without primary cardiac disease in Yantai Yuhuangding Hospital between January 2021 and January 2024 were retrospectively analyzed within 24 h after entering the Pediatric Intensive Care Unit (PICU). The children were divided into normal and abnormal groups according to the myocardial marker results. The abnormal group was further divided into the cTnI-elevated, CK-MB-elevated, single-elevated (cTnI- or CK-MB-elevated) and double-elevated (cTnI- and CK-MB-elevated) groups. The differences in the clinical indicators and their relationships with prognosis for the groups were compared. The incidence of myocardial injury among the critically ill children without primary cardiac disease was 55.1%. The incidence of myocardial injury in children with infectious diarrhea combined with moderate and severe dehydration reached 85.19%. The pediatric critical illness score; frequency of use of vasoactive drugs; hypotension, shock, heart failure, respiratory failure, and multiple organ dysfunction syndrome; and mortality indexes differed significantly for the normal and abnormal myocardial marker groups (P < 0.05). The single-elevated and normal groups only showed a difference in mortality (P < 0.017). The cTnI and CK-MB concentrations were negatively correlated with prognosis (P < 0.01). Myocardial injury, as evidenced by elevated cardiac biomarkers, is common in critically ill children without primary cardiac illness. cTnI and CK-MB are associated with outcomes. Shock, heart failure, and multiple organ dysfunction syndromes are independently associated with simultaneous elevations of CK-MB and cTnI concentrations. Further prospective studies are needed to elucidate the clinical utility of these biomarkers.

Enhanced therapeutic efficacy of SERCA2a gene-modified adipose-derived mesenchymal stem cell exosomes in doxorubicin-induced cardiomyopathy in male albino rats.

Worldwide, cancer is still the primary cause of death, and one of the most widely used anthracyclines for treating cancer is doxorubicin (DOX). But a major worry is DOX-induced cardiomyopathy, which is primarily resulted from an excess of reactive oxygen species. Heart sarcoplasmic reticulum calcium ion ATPase2a (SERCA2a) controls the amount of calcium ions stored in the sarcoplasmic reticulum (SR). This study aims to evaluate and compare the efficacy of SERCA2a gene modified adipose mesenchymal stem cell-derived exosomes (AMSCs-dE) to nontransfected AMSCs-dE, in DOX induced cardiomyopathy in adult male albino rat. Thirty one adult male albino rats were randomly divided into control group and DOX group that further subdivided into three DOX, AMSCs-dE and SERCA2a AMSCs-dE subgroups. AMSCs-dE were administered intravenously (IV). The levels of serum creatine kinase MB (CK-MB) were assessed after DOX injection and before sacrifice. Cardiac muscle samples were taken for histological analysis using Masson's trichrome and hematoxylin and eosin stains two months after the experiment. Proliferating cell nuclear antigen (PCNA) and connexin 43 were stained using immunohistochemistry. The expression of TNF and SERCA2a genes and proteins was measured by real-time polymerase chain reaction (PCR) and Western blot (Wb) analysis, respectively. Fluorescent microscopy demonstrated non-transfected and transfected exosomes labeled with PKH26 and GFP, respectively, in culture and cardiac muscle. DOX induced myocarditis progressing to degenerative and fibrotic changes in cardiac muscle that regressed in response to AMSCs-dE therapy. However, SERCA2a gene modified AMSCs-dE treatment reversed the mentioned parameters to nearly its normal level. These findings suggest that SERCA2a gene modification enhances the therapeutic efficacy of AMSCs-dE in treating DOX-induced cardiomyopathy.

Astaxanthin ameliorated isoproterenol induced myocardial infarction via improving the mitochondrial function and antioxidant activity in rats.

The present study evaluated the cardioprotective effect of astaxanthin (ASX) against isoproterenol (ISO) induced myocardial infarction in rats via the pathway of mitochondrial biogenesis as the possible molecular target of astaxanthin. The control group was injected with normal physiological saline subcutaneously for 2 days. The second group was injected with ISO at a dose of 85 mg/kg bwt subcutaneously for 2 days. The third, fourth and fifth groups were supplemented with ASX at doses of 10, 20, 30 mg/kg bwt, respectively daily by oral gavage for 21 days then injected with ISO dose of 85 mg/kg bwt subcutaneously for 2 successive days. Isoproterenol administration in rats elevated the activities of Creatine kinase-MB (CK-MB), aspartate transaminase (AST), lactate dehydrogenase (LDH), and other serum cardiac biomarkers Troponin-I activities, oxidative stress biomarkers, malondialdehyde(MDA), Nuclear factor-kappa B (NF-KB), while it decreased Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), Nuclear factor erythroid-2-related factor 2 (Nfe212), mitochondrial transcriptional factor A (mt TFA), mitochondrial DNA copy number and glutathione system parameters. However, Astaxanthin decreased the activities of serum AST, LDH, CK-MB, and Troponin I that elevated by ISO. In addition, it increased glutathione peroxidase and reductase activities, total glutathione and reduced GSH content, and GSH/GSSG ratio, mtDNA copy number, PGC-1α expression and Tfam expression that improved mitochondrial biogenesis while it decreased GSSG and MDA contents and NF-KB level in the cardiac tissues. This study indicated that astaxanthin relieved isoproterenol induced myocardial infarction via scavenging free radicals and reducing oxidative damage and apoptosis in cardiac tissue.

Modeling creatine-kinase MB concentrations following coronary artery bypass grafting

BackgroundAn increase in cardiac biomarkers is a prerequisite for diagnosing periprocedural myocardial infarction (PMI) after coronary artery bypass grafting (CABG). Early-phase risk detection may be aided by modeling time-dependent serum creatine kinase-MB (CK-MB) concentrations. This study aimed to model the kinetics of CK-MB while identifying its influencing factors. MethodsPatients who underwent elective CABG and had CK-MB measurements within 72 hours postoperatively were included. The primary outcome was the modeled post hoc kinetics of CK-MB in patients without potential PMI. These patients were defined as having no potential PMI based on the absence of ischemic electrocardiographic abnormalities, imaging abnormalities, in-hospital cardiac arrest, mortality, or postoperative unplanned catheterization. A web-based application was created using mixed-effect modeling to provide an interactive and individualized result. ResultsA total of 1589 CK-MB measurements from 635 patients who underwent elective isolated CABG were available for analysis. Of these, 609 patients (96%) had no potential PMI and 26 (4%) had potential PMI. Male sex, aortic cross-clamp time, and cardioplegia type significantly impacted CK-MB concentrations. The diagnostic accuracy of the model had an area under the receiver operating characteristic curve of 82.8% (95% confidence interval, 72.6%-90.2%). A threshold of 7 μg/L yielded a sensitivity of 94% and a specificity of 80% (positive predictive value, 17%; negative predictive value, 99%) for excluding potential PMI in our study population. ConclusionsCK-MB release after CABG depends on the timing of measurement, patient sex, aortic cross-clamp time, and cardioplegia type. The model (available at https://www.cardiomarker.com/ckmb) can be validated, reproduced, refined, and applied to other biomarkers.

Dibenzazepine, a γ-Secretase Enzyme Inhibitor, Protects Against Doxorubicin-Induced Cardiotoxicity by Suppressing NF-κB, iNOS, and Hes1/Hey1 Expression.

Doxorubicin (DOX) is an effective chemotherapeutic drug; however, its cardiotoxicity and resistance compromise its therapeutic index. The Notch pathway was reported to contribute to DOX cancer resistance. The role of Notch pathway in DOX cardiotoxicity has not been identified yet. Notch receptors are characterized by their extracellular (NECD) and intracellular(NICD) domains (NICD). The γ-secretase enzyme helps in the release of NICD. Dibenzazepine (DBZ) is a γ-secretase inhibitor. The present study investigated the effect of Notch pathway inhibition on DOX cardiotoxicity. Twenty-four male Wistar rats were divided into four groups: control group, DOX group, acute cardiotoxicity was induced by a single dose of DOX (20 mg/kg) i.p., DOX (20 mg/kg) plus DBZ group, and DBZ group. The third and fourth groups received i.p. injection of DBZ daily for 14 days at 2 mg/kg dose. DOX cardiotoxicity increased the level of serum creatine kinase-MB and cardiac troponin I, and it was confirmed by the histopathological examination. Moreover, the antioxidants glutathione peroxidase and superoxide dismutase levels were markedly decreased, and the inflammatory markers, inducible nitric oxide synthase, nuclear factor-ķB, and tumor necrosis factor-α were markedly increased. Furthermore, DOX increased BAX protein and downregulated BCL-2. In addition, DOX upregulated Notch pathway-related parameters: Hes1 and Hey1 mRNA levels, and increased Hes1 protein levels. DBZ ameliorated DOX-induced cardiotoxicity, evidenced by reducing the cardiac injury biomarkers, improving cardiac histopathological changes, correcting antioxidant levels, and reducing inflammatory and apoptotic proteins. Our study indicates the protective effect of Notch inhibitor against DOX-induced cardiotoxicity.

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

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

Protective effects of 3, 4-dihydroxybenzoic acid on myocardial infarction induced by isoproterenol in rats.

Despite considerable advances in interventions and treatment, there is a high mortality rate in patients with myocardial infarction (MI). This is the first study to investigate the protective effects of 3, 4-dihydroxybenzoic acid against isoproterenol induced MI in rats. MI was induced by isoproterenol (100-mg/kg body weight) in rats. Then, rats were treated with 3, 4-dihydroxybenzoic acid (16-mg/kg body weight) for 2 weeks. Serum creatine kinase-MB, cardiac troponin-T, cardiac troponin-I, and heart thiobarbituric acid reactive substances were significantly (p < 0.05) increased and heart superoxide dismutase and catalase activities were significantly (p < 0.05) reduced in isoproterenol-induced myocardial infarcted rats. Isoproterenol induction significantly (p < 0.05) elevated the plasma homocysteine and serum high sensitivity-C-reactive protein levels. Furthermore, an enzyme-linked immunosorbent assay, reverse transcription polymerase chain study, and immunohistochemical (IHC) staining revealed significantly (p < 0.05) elevated levels and expression of serum/myocardial nuclear factor-κB, tumor necrosis factor-alpha, interleukin-1 beta, and Interleukin-6 and significantly (p < 0.05) reduced levels/expression of serum/myocardial interleukin-10 in myocardial infarcted rats. Nevertheless, isoproterenol-induced rats treated with 3, 4-dihydroxybenzoic acid considerably (p < 0.05) attenuated all the biochemical, molecular, and IHC parameters investigated and inhibited oxidative stress and inflammation and protected the heart, through its antioxidant and anti-inflammatory mechanisms.

Generation of cardiomyocytes from stem cells cultured on nanofibrous scaffold: Experimental approach for attenuation of myocardial infarction

The current study was constructed to fabricate polyamide based nanofibrous scaffolds (NS) and to define the most promising one for the generation of cardiomyocytes from adipose tissue derived mesenchymal stem cells (ADMSCs). This purpose was extended to assess the potentiality of the generated cardiomyocytes in relieving myocardial infarction (MI) in rats. Production and characterization of NSs were carried out. ADMSCs were cultured on NS and induced to differentiate into cardiomyocytes by specific growth factors. Molecular analysis for myocyte-specific enhancer factor 2 C (MEF2C) and alpha sarcomeric actin (α-SCA) expression was done to confirm the differentiation of ADMSCs into cardiomyocytes for further transplantation into MI induced rats. Implantation of cells in MI afflicted rats boosted heart rate, ST height and PR interval and lessened P duration, RR, QTc and QRS intervals. Also, this type of medication minified serum lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) enzymes activity as well as serum and cardiac troponin T (Tn-T) levels and upraised serum and cardiac α-SCA and cardiac connexin 43 (CX 43) levels. Microscopic feature of cardiac tissue sections of rats in the treated groups revealed great renovation in the cardiac microarchitecture. Conclusively, this attempt gains insight into a realistic strategy for recovery of MI through systemic employment of in vitro generated cardiomyocytes.

The β2-adrenergic receptor agonist formoterol attenuates necrosis and apoptosis in the rat myocardium under experimental stress-induced cardiac injury.

Currently, there is no effective therapy for takotsubo syndrome (stress-induced cardiac injury in humans) in the clinics. It has previously been shown that β2-adrenergic receptor (β2-AR) agonist formoterol reduces cardiomyocyte injury in experimental takotsubo syndrome. The aim of this study was to investigate whether formoterol prevents apoptosis and necrosis of cardiomyocytes and endothelial cells in stress-induced cardiomyopathy. Stress-induced cardiac injury was induced by immobilization of rats for 2, 6, and 24 hours. The myocardium of stressed rats showed a reduction in contractility and histological manifestations of cardiomyocyte damage: karyopyknosis, perinuclear edema of cardiomyocytes and endothelial cells, and microcirculation disturbances augmented with extended exposure to stress. In addition, apoptosis of endothelial cells was detected 6hours after the onset of stress and peaked at 24 hours. Apoptosis of cardiomyocytes significantly gained only after 24 hours of stress exposure. These morphological alterations were associated with increased levels of serum creatine kinase-MB, syndecan-1, and thrombomodulin after 24 hours of stress. Administration of β2-AR agonist formoterol (50 μg/kg) four times during 24-hour stress exposure led to the improvement in myocardial inotropy, decrease in the severity of histological signatures, reduction in the number of TUNEL-positive cardiomyocytes, serum creatine kinase-MB, syndecan-1, and thrombomodulin levels. Present data suggest that apoptosis and necrosis of cardiomyocytes and necrosis of endothelial cells in stress-induced cardiac injury can be mitigated by activation of the β2-AR. However, formoterol did not eliminate completely cardiomyocyte apoptosis, histological alterations, or endothelium injury markers under stress.

LncRNA NEAT1/miR-211/IL-10 Axis Regulates Inflammation of Peripheral Blood Mononuclear Cells in Acute Myocardial Infarction.

This study aimed to explore the expression of long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) in patients with acute myocardial infarction (AMI) and its inflammatory regulation mechanism through miR-211/interleukin 10 (IL-10) axis.A total of 75 participants were enrolled in this study: 25 healthy people in the control group, 25 patients with stable angina pectoris (SAP) in the SAP group, and 25 patients with AMI in the AMI group. Real-time qPCR was used to detect mRNA expression levels of NEAT1, miR-211, and IL-10. The interaction between miR-211, NEAT1, and IL-10 was confirmed by dual-luciferase reporter assay, and protein expression was detected using western blot.High expression of NEAT1 in peripheral blood mononuclear cells (PBMCs) of patients with AMI was negatively related to serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α), IL-6, and IL-1β and was positively correlated with left ventricular ejection fraction (LVEF). In THP-1 cells, miR-211 was confirmed to target and inhibit IL-10 expression. NEAT1 knockdown and miR-211-mimic markedly decreased IL-10 protein levels, whereas anti-miR-211 markedly increased IL-10 protein levels. Importantly, miR-211 level was negatively related to NEAT1 and IL-10 levels, whereas IL-10 level was positively related to the level of NEAT1 expression in PBMCs of patients with AMI.LncRNA NEAT1 was highly expressed in PBMCs of patients with AMI, and NEAT1 suppressed inflammation via miR-211/IL-10 axis in PBMCs of patients with AMI.

Glycyrrhizin Ameliorates Cardiac Injury in Rats with Severe Acute Pancreatitis by Inhibiting Ferroptosis via the Keap1/Nrf2/HO-1 Pathway.

Severe acute pancreatitis (SAP) is a potential fatal gastrointestinal disease that is usually complicated by myocardial injury and dysfunction. Due to the lack of understanding of the mechanism of SAP-associated cardiac injury (SACI), there is still no complete treatment. To explore the alleviative effect and anti-ferroptosis mechanism against SACI of glycyrrhizin (GL), an inhibitor of oxidative stress. The SAP model was established by perfusing 5% sodium taurocholate into biliopancreatic duct in rats. H&E staining and serum assays were used to assess the injury changes of pancreas and heart. Echocardiography was used to evaluate the cardiac function. Transmission electron microscopy (TEM) and oxidative stress assays were used to investigate the ferroptosis-related morphological and biochemical changes. Western blot and immunofluorescence were performed to analyzed the expression of ferroptosis-related proteins. Significant myocardial impairment was found in SAP rats according to increased histopathological scores, serum creatine kinase-MB (CK-MB) and cardiac troponin-I (cTnI) levels, and a decreased fractional shortening and ejection fraction. The decreased mitochondrial cristae and significant expression changes of ferroptosis-related proteins confirmed the presence of ferroptosis in SACI. GL treatment attenuated above-mentioned cardiac tissues damage by inhibiting ferroptosis via restoring the expression of Nrf2 and HO-1 in vivo and in vitro. Treating with ML385 (a Nrf2 inhibitor) or transfecting with siRNA-Nrf2 reversed the protective effect of GL. Our findings demonstrate the involvement of ferroptosis in SACI and suggest a potential role for GL in the treatment of SACI by supressing ferroptosis via Keap1/Nrf2/HO-1 pathway.

Imatinib pharmacokinetics and creatine kinase levels in chronic myeloid leukemia patients: implications for therapeutic response and monitoring

BackgroundImatinib treatment for certain cancers can lead to elevated creatine kinase (CK) levels, potentially indicating muscle injury, and ongoing research aims to understand the correlation between imatinib levels and creatine kinase to assess its impact on treatment response.MethodsThis single-center observational study involved 76 chronic myeloid leukemia (CML) patients receiving imatinib treatment, focusing on evaluating drug and metabolite levels using liquid chromatography–mass spectrometry (LC–MS-MS) instrumentation. Serum CK and creatine kinase-MB (CK-MB) levels were assessed using Colorimetric kits.ResultsCK and CK-MB levels were measured, CK showed a median value of 211.5 IU/l and CK-MB showed a median value of 4.4 IU/l. Comparing low and high CK groups, significant differences were found in peak and trough plasma concentrations of imatinib and its metabolites. Correlations between CK levels and pharmacokinetic parameters were explored, with notable associations identified. Binary logistic regression revealed predictors influencing the therapeutic response to imatinib and categorized expected CK levels into high or low, with peak levels of imatinib emerging as a significant predictor for CK level categorization.ConclusionThe study highlights the link between imatinib’s pharmacokinetics and elevated CK levels, indicating a possible correlation between specific metabolites and improved treatment response. Individualized monitoring of CK levels and imatinib pharmacokinetics could enhance care for CML patients.

Methanolic extract of Cleome droserifolia mitigates epinephrine-induced cardiac injury

Ethnopharmacological relevanceCleome droserifolia treatment has potent antioxidant, antimicrobial, and immunomodulatory potentials, which can help recover the general health status. Aim of the studyThis research aims to estimate the potential cardioprotective properties of the methanolic extract of Cleome droserifolia (MEC) against epinephrine-induced cardiac injury (MI) in rats. Materials and methodsThirty-six male Wistar rats were separated equally into 6 groups. The control group (Cont) received oral distilled water for 30 uninterrupted days and was administered subcutaneous saline on the 31st and 32nd days. The MEC 100 group received MEC 100 mg/kg, P.O., for 30 uninterrupted days and administered subcutaneous saline on the 31st and 32nd days. The MEC 200 group received MEC 200 mg/kg, P.O. for 30 uninterrupted days and subcutaneous saline was administered on the 31st and 32nd days. The epinephrine group (EP) received distilled water orally for 30 uninterrupted days and administered subcutaneous epinephrine (2 mg/kg, s.c.) divided into two doses (1 mg/kg, s.c) each on the 31st and 32nd days. MEC 100+Ep group received MEC 100 mg/kg, P.O., for 30 uninterrupted days and administered subcutaneous epinephrine (2 mg/kg, s.c.) divided into two doses (1 mg/kg, s.c) each on the 31st and 32nd days. The MEC 200+EP received MEC 200 mg/kg, P.O. for 30 uninterrupted days and administered subcutaneous epinephrine (2 mg/kg, s.c.) divided into two doses (1 mg/kg, s.c) each on the 31st and 32nd days. Electrocardiography (ECG), biochemical, oxidative stress, inflammatory mediators, histopathological, immunohistochemical analysis and the expression of phosphoinositide 3-kinases (PI3K) and protein kinase B (AKT) were assessed. ResultsMEC reversed epinephrine-induced lessening of heart rate, prolonged QT interval and ST displacement. Pretreatment with MEC significantly reduced serum aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) levels in MI rats. The MEC pretreatment promoted total antioxidant capacity (TAC), glutathione (GSH), and total oxidant status (TOS). In addition, it reduced interleukin-1β (IL-1β), interleukin-6 (IL-6), malondialdehyde (MDA), and tumour necrosis factor (TNF-α) in MI rats. Furthermore, MEC statistically reduced immunohistochemical promotion of nuclear factor–κB (NF-κB) and expression of AKT and PI3K in cardiac tissue and perfected histopathological changes. ConclusionThe MEC, rich in phenolic and flavonoid contents, had a cardioprotective effect on rats suffering from epinephrine-induced MI. Such effect was achieved via improving cardiac function, antioxidant status, attenuating ECG pattern and histological picture, as well as reducing IL-6, IL-1β, TNF-α and NF-κB, which its antioxidant and anti-inflammatory potential may partly arbitrate.

Cardioprotective role of royal jelly in the prevention of celecoxib-mediated cardiotoxicity in adult male albino rats

BackgroundCelecoxib, a cyclooxygenase-2 selective inhibitor non-steroidal anti-inflammatory drugs, is used for the management of short- and long-term pain as well as in other inflammatory conditions. Unfortunately, its chronic use is highly associated with serious abnormal cardiovascular events. The current study was designed to explore the effect of long-term administration of celecoxib on the cardiac tissues of male albino rats. The study also examined the alleged cardioprotective effect of royal jelly.MethodsThirty, male albino rats were randomly divided into 3 equal groups; 10 each: (1) rats served as the control group and received no drug; (2) rats received celecoxib (50 mg/kg/day, orally), for 30 consecutive days; (3) rats received celecoxib (50 mg/kg/day, orally) plus royal jelly (300 mg/kg/day, orally) for 30 consecutive days. Sera were collected to assay cardiac enzymes and oxidant/antioxidant status. Rats were euthanatized and cardiac tissues were dissected for quantitative estimation of apoptotic genes (Bax) and anti-apoptotic gene (Bcl-2).ResultsLong-term celecoxib administration caused cardiotoxicity in male albino rats as manifested by significant elevation of serum levels of creatine phosphokinase (CPK), creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH), with ameliorative effects of royal jelly against celecoxib-induced cardiotoxicity as manifested by significantly decrease in serum CPK, CK-MB, and LDH levels. It also showed a significant decrease in the oxidative stress indicator malondialdehyde (MDA) levels and the bax gene. Additionally, it demonstrated significant increases in the bcl-2 gene and superoxide dismutase (SOD) levels, which contribute to its therapeutic effects against celecoxib-induced cardiotoxicity.ConclusionLong-term celecoxib administration caused cardiotoxicity in male albino rats with protective effect of royal jelly being given together. It could be concluded that royal jelly may prove a useful adjunct in patients being prescribed celecoxib.Trial registrationNot applicable.

Ocimum gratissimum L. leaf flavonoid-rich extracts reduced the expression of p53 and VCAM in streptozotocin-induced cardiomyopathy rats

BackgroundThis study aimed to investigate the potential cardioprotective effects of flavonoid-rich extracts from Ocimum gratissimum leaves in a streptozotocin-induced diabetic rat model by assessing redox stress biomarkers, ATPase activities, gene expression levels, enzyme activities, and histopathological changes. MethodsDiabetic rats were administered low (LDOGFL) and high (HDOGFL) doses of O. gratissimum leaf flavonoid-rich extracts, metformin (MET), or served as diabetic (DC) and normal (NC) controls for twenty-one days. Various cardiac parameters were evaluated, including redox stress biomarkers, ATPase activities, relative gene expression of p53 and VCAM, phosphatase activities, transaminase activities, serum creatine kinase-MB (CKMB) activities, cardiac troponin levels, and natriuretic peptide levels. Additionally, heart histoarchitecture was also examined using hematoxylin and eosin (H&E) staining. ResultsFlavonoid-rich extracts of O. gratissimum significantly (p < 0.05) mitigated redox stress by decreasing malondialdehyde (MDA) levels and increasing reduced glutathione (GSH), glutathione-S-transferase (GST), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities in diabetic treated rats. The extracts also notably (p < 0.05) improved ATPase activities and significantly (p < 0.05) modulated the relative gene expression of p53 and VCAM in diabetic treated rats. Furthermore, diabetic rat administered flavonoid-rich extracts markedly (p < 0.05) attenuated phosphatase activities, transaminase activities, CKMB activities, cardiac troponin levels, and natriuretic peptide levels. Histopathological examination of the diabetic rats revealed improved cardiac histoarchitecture in extract-treated groups compared to diabetic controls. ConclusionThese findings suggest that O. gratissimum leaf flavonoid-rich extracts confer cardioprotective effects in STZ-induced diabetic rats by ameliorating redox imbalance, modulating gene expression, regulating enzyme activities, and preserving cardiac histoarchitecture. These results highlight the potential therapeutic application of O. gratissimum flavonoids in managing diabetes-induced cardiomyopathy.

Beneficial role of amygdalin extracts against animal growth regulator Boldjan induced cardiac toxicity, injury and oxidative stress in male rats.

Millions of individuals have used illicit anabolic-androgenic steroids (AAS), but the long-term cardiovascular associations of these drugs remain incompletely understood. Boldjan is AAS medication which is used in veterinary medicine and by young adults aiming to have a better appearance improving their self-esteem. Therefore; the objective of the current investigation was to examine any potential preventative effects of amygdalin extract against anabolic steroid Boldjan induced cardic toxicity, injury and oxidative stress in male rat. Forty adult male Wistar rats were classified into five groups (Gp1, Control Gp; Gp2, Amygdalin Gp in which rats treated with amygdalin (100mg/kg body weight/day) daily for 2weeks; Gp3, Boldjan Gp in which rats treated with Boldjan (10mg/Kg BW/week) for 4weeks; Gp4, Boldjan+Amygdalin). Boldjan induced a significant rises in serum lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase MB (CK MB), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), and very-low-density lipoprotein-cholesterol (VLDL-C), cardiac injury, and malondialdehyde (MDA) levels and a significant depletion in serum high-density lipoprotein-cholesterol (HDL-C), cardiac reduced glutathione (GSH), Superoxide dismutase (SOD) and catalase (Cat) activities as compared to control Gp. In contrast, Amygdalin significantly reversed the Boldjan induced cardiac toxicity in post treated rats Gp (Boldjan+Amygdalin). Amygdalin could be an efficient preventive supplement for mitigating Boldjan induced cardiac toxicity, possibly via controlling oxidative stress events.

Low Selenium and Low Protein Exacerbate Myocardial Damage in Keshan Disease by Affecting the PINK1/Parkin-mediated Mitochondrial Autophagy Pathway.

Keshan disease (KD) is a myocardial mitochondrial disease closely related to insufficient selenium (Se) and protein intake. PTEN induced putative kinase 1 (PINK1)/Parkin mediated mitochondrial autophagy regulates various physiological and pathological processes in the body. This study aimed to elucidate the relationship between PINK1/Parkin-regulated mitochondrial autophagy and KD-related myocardial injury. A low Se and low protein animal model was established. One hundred Wistar rats were randomly divided into 5 groups (control group, low Se group, low protein group, low Se + low protein group, and corn from KD area group). The JC-1 method was used to detect the mitochondrial membrane potential (MMP). ELISA was used to detect serum creatine kinase MB (CK-MB), cardiac troponin I (cTnI), and mitochondrial-glutamicoxalacetic transaminase (M-GOT) levels. RT-PCR and Western blot analysis were used to detect the expression of PINK1, Parkin, sequestome 1 (P62), and microtubule-associated proteins1A/1B light chain 3B (MAP1LC3B). The MMP was significantly decreased and the activity of CK-MB, cTnI, and M-GOT significantly increased in each experimental group (low Se group, low protein group, low Se + low protein group and corn from KD area group) compared with the control group (P<0.05 for all). The mRNA and protein expression levels of PINK1, Parkin and MAP1LC3B were profoundly increased, and those of P62 markedly decreased in the experimental groups compared with the control group (P<0.05 for all). Low Se and low protein levels exacerbate myocardial damage in KD by affecting the PINK1/Parkin-mediated mitochondrial autophagy pathway.