Creatine kinase-MB Activity Research Articles

Minocycline alleviates lipopolysaccharide-induced cardiotoxicity by suppressing the NLRP3/Caspase-1 signaling pathway.

Minocycline (Min), as an antibiotic, possesses various beneficial properties such as anti-inflammatory, antioxidant, and anti-apoptotic effects. Despite these known qualities, the precise cardioprotective effect and mechanism of Min in protecting against sepsis-induced cardiotoxicity (SIC) remain unspecified. To address this, our study sought to assess the protective effects of Min on the heart. Lipopolysaccharide (LPS) was utilized to establish a cardiotoxicity model both in vivo and in vitro. Min was pretreated in the models. In the in vivo setting, evaluation of heart tissue histopathological injury was performed using hematoxylin and eosin (H&E) staining and TUNEL. Immunohistochemistry (IHC) was employed to evaluate the expression levels of NLRP3 and Caspase-1 in the heart tissue of mice. During in vitro experiments, the viability of H9c2 cells was gauged utilizing the CCK8 assay kit. Intracellular ROS levels in H9c2 cells were quantified using a ROS assay kit. Both in vitro and in vivo settings were subjected to measurement of oxidative stress indexes, encompassing glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. Additionglly, myocardial injury markers like lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB) activity were quantified using appropriate assay kits. Western blotting (WB) analysis was conducted to detect the expression levels of NOD-like receptor protein-3 (NLRP3), caspase-1, IL-18, and IL-1β, alongside apoptosis-related proteins such as Bcl-2 and Bax, and antioxidant proteins including superoxide dismutase-1 (SOD-1) and antioxidant proteins including superoxide dismutase-1 (SOD-2), both in H9c2 cells and mouse heart tissues. In vivo, Min was effective in reducing LPS-induced inflammation in cardiac tissue, preventing cell damage and apoptosis in cardiomyocytes. The levels of LDH and CK-MB were significantly reduced with Min treatment. In vitro studies showed that Min improved the viability of H9C2 cells, reduced apoptosis, and decreased ROS levels in these cells. Further analysis indicated that Min decreased the protein levels of NLRP3, Caspase-1, IL-18, and IL-1β, while increasing the levels of SOD-1 and SOD-2 both in vivo and in vitro. Min alleviates LPS-induced SIC by suppressing the NLRP3/Caspase-1 signalling pathway in vivo and in vitro.

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.

Feasibility of aligning creatine kinase MB activity and mass data in multicentre trials using generalized additive modelling.

Elevated serum creatine kinase isoenzyme MB (CK-MB) levels indicate myocardial ischaemia and periprocedural myocardial injury during treatment of heart diseases. We established a method to predict CK-MB mass from activity data based on a prospective pilot study in order to simplify multicentre trials. 38 elective cardiac surgery patients without acute myocardial ischaemia and terminal renal failure were recruited. CK-MB mass and activity were determined in venous blood samples drawn preoperatively, postoperatively, 6 h post-op, and 12 h post-op. Linear regression and generalized additive models (GAMs) were applied to describe the relationship of mass and activity. Influences of demographic and perioperative factors on the fit of GAMs was evaluated. The agreement of predicted and measured CK-MB masses was assessed by Bland-Altman analyses. Linear regression provided an acceptable overall fit (r2 = 0.834) but showed deviances at low CK-MB levels. GAMs did not benefit from the inclusion of age, body mass index and surgical times. The minimal adequate model predicted CK-MB masses from activities, sex and sampling time with an r2 of 0.981. Bland-Altman analyses confirmed narrow limits of agreement (spread: 8.87 µg/l) and the absence of fixed (P = 0.41) and proportional (P = 0.21) biases. GAM-based modelling of CK-MB data in a representative patient cohort allowed to predict CK-MB masses from activities, sex and sampling time. This approach simplifies the integration of study centres with incompatible CK-MB data into multicentre trials in order to facilitate inclusion of CK-MB levels in statistical models.

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<0.05) and cardiac tissue MDA (p>0.05), NO (p<0.01), caspase 3 (p<0.01), DNA fragmentation (p<0.001), cathepsin B (p<0.05) and L (p<0.05) activities were increased and SOD (p<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.

Comparative efficacy of sweated and non-sweated Salvia miltiorrhiza Bge. extracts on acute myocardial ischemia via regulating the PPARα/RXRα/NF-κB signaling pathway

Salvia miltiorrhiza Bge. (S. miltiorrhiza) is a well-known traditional Chinese medicine for the treatment of cardiovascular diseases. The processing of S. miltiorrhiza requires the raw herbs to sweat first and then dry. The aim of this study was to investigate the anti-acute myocardial ischemia (AMI) of S. miltiorrhiza extracts (including tanshinones and phenolic acids) before and after sweating, and to further explore whether the “sweating” primary processing affected the efficacy of S. miltiorrhiza. The AMI animal model was established by subcutaneous injection of isoprenaline hydrochloride (ISO). After treatment, the cardiac function of rats was evaluated by electrocardiogram (ECG), biochemical, and histochemical analysis. Moreover, the regulation of S. miltiorrhiza extracts on the peroxisome proliferator-activated receptor α (PPARα)/retinoid X receptor α (RXRα)/nuclear transcription factor-kappa B (NF-κB) signaling pathway of rats was assessed by the Western blotting. The results showed that sweated and non-sweated S. miltiorrhiza extracts including tanshinones and phenolic acids significantly reduced ST-segment elevation in ECG and the myocardial infarction area in varying degrees. Meanwhile, sweated and non-sweated S. miltiorrhiza reversed the activities of aspartate transaminase (AST), lactic dehydrogenase (LDH), creatine kinase-MB (CK-MB), and superoxide dismutase (SOD), as well as the levels of interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in AMI rats. Concurrently, the results of Western blotting revealed that S. miltiorrhiza extracts regulated the PPARα/RXRα/NF-κB signaling pathway to exert an anti-inflammatory effect. Most importantly, sweated S. miltiorrhiza tanshinones extracts are more effective than the non-sweated S. miltiorrhiza, and the anti-inflammatory efficacy of tanshinones extract was also better than that of phenolic acid extract. Although phenolic acid extracts before and after sweating were effective in anti-AMI, there was no significant difference between them. In conclusion, both tanshinones and phenolic acids extracts of sweated and non-sweated S. miltiorrhiza promote anti-oxidative stress and anti-inflammatory against AMI via regulating the PPARα/RXRα/NF-κB signaling pathway. Further, the comparations between sweated and non-sweated S. miltiorrhiza extracts indicate that sweated S. miltiorrhiza tanshinones extracts have better therapeutic effects on AMI.

Evaluation of creatine kinase-MB activity and cortisol level in hypertensive Mycobacterium tuberculosis patients receiving treatment in Nnewi

Evaluation of creatine kinase-MB activity and cortisol level in hypertensive Mycobacterium tuberculosis patients receiving treatment in Nnewi

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.

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.

Evaluation of Creatine Kinase-MB Activity and Cortisol Level in Hypertensive Mycobacterium Tuberculosis Patients Receiving Treatment in Nnewi.

Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), imposes a health challenge globally. Tuberculosis is an infectious disease that most often affects the lungs, and it spreads through the air when infected people cough, sneeze, or spit. This study was aimed at evaluating creatine kinase-MB (CK-MB) activity and cortisol levels in Mycobacterium tuberculosis patients receiving therapy at Nnewi. A cross-sectional study involved 90 participants consisting of 45 TB+ individuals and 45 healthy controls. A questionnaire was used to obtain the age, sex, and other vital information needed for the study. The body mass index (BMI) of the participants was calculated. Their systolic and diastolic blood pressure was obtained using an Accu-Answer automatic blood pressure monitor. Ziehl-Nelseen (ZN) sputum smear microscopy determined Mycobacterium tuberculosis infection and confirmed positive using GeneXpert. Plasma cortisol level was determined using an Enzyme-linked immunosorbent assay whereas plasma CK-MB activity was determined spectrophotometrically. Independent t-test and Pearson`s correlation coefficient were used for statistical analysis. Significant levels were considered at p &lt; 0.05. Data was presented as mean ± standard deviation. The mean value of the diastolic blood pressure (DBP) of the TB+ participants was significantly lower (75.53 ± 14.04) compared with the control (81.53 ± 6.10) (p &lt; 0.05). No significant difference was observed in the mean values of plasma cortisol and CK-MB activity (9.37±1.26) (18.99±1.26) of the TB+ participants compared with control (9.28±6.92) (18.81±1.45) (p&gt;0.05). There was a moderate positive correlation between systolic blood pressure (SBP) and DBP (r = 0.50; p = 0.01) in the test group and a strong positive correlation between SBP and DBP in the control. SBP and cortisol showed a moderate positive correlation with DBP and cortisol in the test group. In conclusion, there was no predisposition to acute myocardial infarction and inflammation in the subjects studied.

Association between apelin-12 and creatine kinase-MB, depending on success of reperfusion in STEMI patients.

Acute myocardial infarction is characterised by an imbalance in the supply and demand of oxygen in the heart. It requires urgent reperfusion, and poor outcomes are attributed to myocardial ischaemia-reperfusion injury. We aimed to evaluate the association between apelin-12 levels and creatine kinase-MB activity in predicting the effectiveness of reperfusion therapy in ST-segment elevation myocardial infarction (STEMI) patients. In this study we included 72 patients with the following criteria: chest pain suggestive of myocardial ischaemia for at least 30 minutes, an electrocardiogram with ST-segment elevation (measured at the J-point) ≥ 2 mm in leads V2-V3 and/or ≥ 1 mm in the other leads, rise of specific biomarkers such as cardiac troponin and the MB fraction of creatine kinase (CK-MB), and those who underwent reperfusion therapy. Blood samples for the measurement of apelin-12 and creatine kinase-MB were collected 12 hours after the reperfusion therapy. In patients with thrombolysis in myocardial infarction (TIMI) flow grade ≤ 2, the median of the apelin-12 level was 1.80 ng/ml (0.46-9.20), and with TIMI flow 3, it was 5.76 ng/ml (1.14-15.2). Variability was observed in the apelin values (Mann-Whitney test) based on TIMI flow grade (p < 0.001), while no variability was observed for creatine kinase-MB (p < 0.18). The degree of association between apelin-12 and creatine kinase-MB levels was analysed with Pearson's correlation, enabling us to determine patients with successful reperfusion (determined as TIMI flow 3) (p < 0.004), and those with unsuccessful reperfusion (with TIMI flow ≤ 2) (p = 0.86). In STEMI patients undergoing reperfusion therapy, Apelin-12 level was associated with creatine kinase-MB activity according to the success of the reperfusion.

Impacts of dietary lipids derived from animal or vegetable sources on healthy rats

ABSTRACT This study sought to assess the health impact of feeding adult healthy rats with either 7% (w/w) animal-derived fat (subcutaneous rump fat or peri-kidney fat) from domestic buffalo or vegetable oil (corn oil or olive oil) for 8 weeks on bioactivity; lipid profile; hepatic and cardiac histological changes. Twenty-four male albino rats were randomly categorized into four dietary groups (six rats/group): 1) diet contains 7% (w/w) corn oil; 2) diet contains 7% (w/w) olive oil; 3) diet contains 7% (w/w) subcutaneous rump fats and 4) diet contains 7% (w/w) Peri-kidney fats. Animal fats intake significantly increased serum total lipids (TL), triacylglycerol (TG), low-density lipoprotein cholesterol (LDLC), cardiac troponin-I (CTn-I) concentration as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), creatine kinase MB (CK-MB) and lactate dehydrogenase (LDH) activities compared to vegetable oils intake. In histopathological research, liver and heart sections excised from rats consumed animal-derived fats showed several signs of extensive damage, including inflammation as well as fibrosis. Compared to animal-derived fats, vegetable oils consumption markedly increased serum high-density lipoprotein cholesterol (HDLC) concentration and exhibited a potential attenuation effect on liver and heart enzymes activities and a potential role in the reduction of TG in the bloodstream of rats as well as revealed normal liver and heart histopathological architectures. In conclusion, this study suggests that, replacing animal fats, especially peri-kidney fat with vegetable oils, particularly olive oil in diets, liver and heart can be protected.

Analysis of the toxic effects of fluoroquinolones in laboratory rabbit models

Introduction. Fluoroquinolones are antibacterials for which the development of cardiotoxicity, hepatotoxicity, nephrotoxicity and connective tissue damage has been noted. The likely mechanism for the development of these reactions is magnesium metabolism disorder. An available method to detect fluoroquinolones toxicity in animal experiments is a blood biochemical test.The aim of the work was to identify the biochemical signs of the toxic effects of fluoroquinolones in laboratory rabbit models.Materials and methods. Twenty male rabbits randomised into three groups were included in the study: 6 control animals; 7 rabbits treated with ciprofloxacin 150 mg/kg 14 days; 7 rabbits treated with levofloxacin 150 mg/kg 14 days. Serum levels of albumin, alanine aminotransferase (liver damage marker), creatinine (nephrotoxicity marker), creatine kinase MB (cardiotoxicity marker), matrix metalloproteinase 9 (connective tissue damage marker), serum and plasma magnesium content were studied in this work. Data are presented as mean (standard deviation).Results. Serum levels of albumin, alanine aminotransferase and creatinine did not change during the experiment. Rabbits treated with levofloxacin had 2.0–2.5 times lower values of CF creatine kinase activity than control animals. There was double increase of serum concentration of matrix metalloproteinase 9 in ciprofloxacin group in comparison with control (70,17 (20,88) and 38,10 (16,04) ng/ ml, p = 0,019). Magnesium content was unchanged with both fluoroquinolones.Discussion. The absence of signs of hepatotoxicity and nephrotoxicity is consistent with their low frequency of detection in clinical and experimental studies. A decrease in the activity of creatine kinase MB in animals treated with levofloxacin has not been described in the literature. An increase in the concentration of metalloproteinase 9 is evidence of destruction of connective tissue structures. The absence of changes in serum and plasma concentrations of magnesium is explained by the functioning of the systems maintaining the constancy of its content in blood.Conclusion. No biochemical evidence of hepato-, nephro- and cardiotoxic effects of ciprofloxacin and levofloxacin at the doses of 150 mg/kg for 14 days was shown in rabbits; no magnesium metabolism disorders were shown, and the ability of ciprofloxacin to increase the serum content of matrix metalloproteinase type 9 was demonstrated. The proposed model can be used to investigate ways to prevent the toxic effects of fluoroquinolones on connective tissue structures.

Impact of Intratracheal Administration of Polyethylene Glycol-Coated Silver Nanoparticles on the Heart of Normotensive and Hypertensive Mice.

Silver nanoparticles are widely used in various industrial and biomedical applications; however, little is known about their potential cardiotoxicity after pulmonary exposure, particularly in hypertensive subjects. We assessed the cardiotoxicity of polyethylene glycol (PEG)-coated AgNPs in hypertensive (HT) mice. Saline (control) or PEG-AgNPs (0.5 mg/kg) were intratracheally (i.t.) instilled four times (on days 7, 14, 21, and 28 post-angiotensin II or vehicle [saline] infusion). On day 29, various cardiovascular parameters were evaluated. Systolic blood pressure and heart rate were higher in PEG-AgNPs-treated HT mice than in saline-treated HT or PEG-AgNPs-treated normotensive mice. The heart histology of PEG-AgNPs-treated HT mice had comparatively larger cardiomyocyte damage with fibrosis and inflammatory cells when compared with saline-treated HT mice. Similarly, the relative heart weight and the activities of lactate dehydrogenase and creatine kinase-MB and the concentration of brain natriuretic peptide concentration were significantly augmented in heart homogenates of HT mice treated with PEG-AgNPs compared with HT mice treated with saline or normotensive animals exposed to PEG-AgNPs. Similarly, the concentrations of endothelin-1, P-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in heart homogenates were significantly higher than in the other two groups when HT mice were exposed to PEG-AgNPs. Markers of inflammation and oxidative and nitrosative stress were significantly elevated in heart homogenates of HT mice given PEG-AgNPs compared with HT mice treated with saline or normotensive animals exposed to PEG-AgNPs. The hearts of HT mice exposed to PEG-AgNPs had significantly increased DNA damage than those of HT mice treated with saline or normotensive mice treated with AgNPs. In conclusion, the cardiac injury caused by PEG-AgNPs was aggravated in hypertensive mice. The cardiotoxicity of PEG-AgNPs in HT mice highlights the importance of an in-depth assessment of their toxicity before using them in clinical settings, particularly in patients with pre-existing cardiovascular diseases.

Effect of Gallic Acid Pretreatment and SGK1 Enzyme Inhibition on Cardiac Function and Inflammation in a Rat Model of Ischemia-Reperfusion Injury.

Serum and glucocorticoid-induced kinase 1 (SGK1) is an enzyme that may play an important role in ischemic-reperfusion (I/R) injury and myocardial dysfunction. Although many studies have been conducted on individual antioxidants, little attention has been paid to the effects of co-administration of an antioxidant with an SGK1 inhibitor on cardiac function after I/R. This study aimed to determine the effects of gallic acid (as an antioxidant) combined with an SGK1 inhibitor on I/R-induced cardiac dysfunction and inflammation. Sixty male Wistar rats were randomized into 6 groups, pretreated with gallic acid or vehicle for 10 days. Subsequently, the heart was isolated and exposed to I/R. In groups that received the SGK1 inhibitor, the heart was perfused with the SGK1 inhibitor GSK650394, 5 min before induction of ischemia. After that, cardiac function, inflammatory factors, and myocardial damage were evaluated. The combination of these two compounds improved cardiac contractility, heart rate, rate pressure product, left ventricular developed pressure, left ventricular systolic pressure, perfusion pressure, and QRS voltage significantly (P < 0.05). In addition, concomitant therapy of these two agents reduced tumor necrosis factor-alpha and interleukin-6, and the activity of creatine kinase-MB, lactate dehydrogenase, and troponin-I (P < 0.05). The results indicated that administration of gallic acid with the SGK1 inhibitor may have a potentiating effect on the improvement of cardiac dysfunction and I/R-induced inflammation.

Arginine, symmetric and asymmetric dimethylarginine levels in canine leishmaniasis

The study aimed to investigate the levels of arginine, symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA) in dogs with canine leishmaniasis (CanL) and their relationship with some renal and cardiovascular parameters. A total of 60 dogs were enrolled, including 40 with CanL and 20 healthy controls. The CanL group was divided into four stages based on clinical and laboratory findings. The levels of plasma arginine, SDMA, and ADMA were determined by high performance liquid chromatography (HPLC). The data from the healthy group were compared with those from the CanL group, and according to the stages. In dogs with CanL, systolic and diastolic blood pressure, plasma creatinine, cystatin-C, phosphorus, potassium, and low-density lipoprotein concentrations, the urine protein/creatinine ratio, the amount of nitric oxide, and creatine kinase-MB activity were higher, while the high-density lipoprotein concentration was lower compared to healthy controls. The concentration of arginine was low (p < 0.05) and the levels of ADMA (p < 0.001) and SDMA (p < 0.05) were high in dogs with CanL. There were no statistically significant differences in arginine concentration among the different stages of CanL. However, the concentration of plasma ADMA was higher in all stages of CanL compared to the healthy group, and the concentration of plasma SDMA was higher in Stage IV compared to the healthy group and Stage III. The present study demonstrates for the first time a decrease in arginine concentration and an increase in ADMA concentration in dogs with CanL. The increase in SDMA concentration in dogs with CanL was consistent with previous studies. However, compared to other renal parameters, SDMA exhibited limited performance distinguishing between clinical stages of CanL. These findings could be a source for future diagnostic and therapeutic studies to explain the renal and cardiovascular pathophysiology of CanL. Additional clinical studies that include treatment and patient follow-up with an assessment of the acute phase response are needed to provide a more detailed understanding of the changes observed in dogs with CanL.

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.

Feedback Interaction Between Apelin and Endoplasmic Reticulum Stress in the Rat Myocardium.

Apelin is an endogenous active peptide, playing a crucial role in regulating cardiovascular homeostasis. This study aimed to investigate the interaction between apelin and endoplasmic reticulum stress (ERS). Tunicamycin (Tm) and dithiothreitol (DTT) were used to induce ERS in the ex vivo cultured myocardium of rats. Myocardial injury was determined by the activities of lactate dehydrogenase and creatine kinase-MB in the culture medium. The protein levels of an ERS-associated molecule, apelin, and its receptor angiotensin domain type 1 receptor-associated proteins (APJ) in the myocardium were determined by western blot analysis. The level of apelin in the culture medium was determined by enzyme immunoassay. Administration of Tm and DTT triggered ERS activation and myocardial injury, and led to a decrease in protein levels of apelin and APJ, in a dose-dependent manner. Integrated stress response inhibitor, an inhibitor of eukaryotic initiation factor 2α phosphorylation that is commonly used to prevent activation of protein kinase R-like ER kinase cascades, blocked ERS-induced myocardial injury and reduction of apelin and APJ levels. The ameliorative effect of integrated stress response inhibitor was partially inhibited by [Ala]-apelin-13, an antagonist of APJ. Furthermore, apelin treatment inhibited activation of the 3 branches of ERS induced by Tm and DTT in a dose-dependent manner, thereby preventing Tm-induced or DTT-induced myocardial injury. The negative feedback regulation between ERS activation and apelin/APJ suppression might play a critical role in myocardial injury. Restoration of apelin/APJ signaling provides a potential target for the treatment and prevention of ERS-associated tissue injury and diseases.

Cardioprotection by Citrus grandis (L.) Peel Ethanolic Extract in Alloxan-Induced Cardiotoxicity in Diabetic Rats.

Diabetic cardiomyopathy (DCM) pathogenesis is multifarious, and there are insufficient therapeutic options to treat DCM. The present research explored the effects of Citrus grandis peel ethanolic extract (CGPE) in alloxan-induced DCM in rats. Diabetes was triggered by intraperitoneal (i.p.) injection of alloxan (150 mg/kg) in Wistar rats (200-250 g). CGPE (100, 200, and 400 mg/kg) or glibenclamide (Glib, 10 mg/kg) were administered orally for 2 weeks. After the treatment schedule, prooxidants (thiobarbituric acid reactive substances), antioxidants (glutathione, catalase, and superoxide dismutase), and inflammatory markers (tumor necrosis factor-α) were determined in cardiac tissues. Biomarkers of cell death, viz., lactate dehydrogenase (LDH), creatine kinase MB (CK-MB) activity, glucose levels, total cholesterol (TC), and high-density lipoproteins (HDL), were assessed in the blood. Rats administered with alloxan showed a consistent increase in blood glucose level (days 7 and 14) that was lowered considerably (p < 0.001) by CGPE or Glib. Alloxan-induced increase in LDH, CK-MB, TC, and decline in HDL was attenuated (p < 0.001) in rats that were treated with CGPE or Glib. Alloxan significantly (p < 0.001) elevated oxidative stress, inflammation, and reduced antioxidants in the cardiac tissue of rats, and these pathogenic abnormalities were ameliorated (p < 0.001) by CGPE. Histopathological studies showed a decrease in morphological disruptions by alloxan in CGPE-treated rats. CGPE (400 mg/kg) significantly ameliorated biochemical parameters in comparison to the lower doses against alloxan cardiotoxicity. Citrus grandis peel extract can be an alternative in the management of DCM.

Metformin and alpha lipoic acid ameliorate hypothyroidism and its complications in adult male rats.

The current study evaluates the effect of metformin (MET) and /or alpha lipoic acid (ALA) on hypothyroidism and its adverse effects on the cardiac, renal, and, hepatic functions in rats. Rats were divided into five groups: control, rat model of hypothyroidism induced by propylthiouracil (PTU), rat model of hypothyroidism treated with MET, rat model of hypothyroidism treated with ALA, and rat model of hypothyroidism treated with MET and ALA. At the end of the experiment, body weight gain was determined and the blood samples were collected from orbital plexus to measure the serum levels of thyroxine (T4), triiodothyronine (T3) and thyroid stimulating hormone (TSH) by ELISA, glucose level, the activities of lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), and the levels of urea and creatinine spectrophotometrically. Rat model of hypothyroidism revealed a significant decrease in T4 (p < 0.001) and T3 (p < 0.001) and a significant increase in TSH (p < 0.005). This was accompanied by a significant decrease in the body weight gain (p < 0.025) and a significant increase in LDH (p < 0.001), CK-MB (p < 0.001) AST (p < 0.01), ALT (p < 0.016), ALP (p < 0.001), glucose (p < 0.001), urea (p < 0.001) and creatinine (p < 0.001). MET restored T4, T3 and TSH to control values. Treatment with ALA restored T3 and TSH levels. Treatment with Met and /or ALA reduced the levels of glucose, urea and creatinine and the activities of LDH, CK-MB, AST, ALT, and ALP to control-like values. Only ALA improved the reduced body weight gain induced by hypothyroidism. The present findings indicate the ameliorative effects of MET and /or ALA on hypothyroidism and its adverse effects on cardiac, renal and hepatic functions. The online version contains supplementary material available at 10.1007/s40200-022-01063-7.

Empagliflozin alleviates myocardial I/R injury and cardiomyocyte apoptosis via inhibiting ER stress-induced autophagy and the PERK/ATF4/Beclin1 pathway

To explore the mechanisms underlying the specific inhibitor targeting SGLT-2 empagliflozin in alleviating myocardial ischaemia–reperfusion (I/R) injury. A mouse model of I/R injury and H2O2-induced H9C2 cell model were established. The expressions of Bcl-2, Bax, LC3, Beclin1, GRP78, CHOP, PERK, ATF4, ATF6, IREα and P62 were examined by western blot, immunofluorescence or immunohistochemistry staining, respectively. The cardiac function was measured by echocardiography, TCC staining, lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) activity. Cell apoptosis was analysed by TUNEL, Annexin V/propidium iodide (PI) staining and caspase 3 and 9 activities. CCK-8 assay was used for analysing cell viability. PBA, TUDC and 3-MA were utilised for blocking ER stress and autophagy, respectively. Empagliflozin suppressed myocardial I/R injury in vivo and H2O2-induced cardiomyocyte apoptosis in vitro. Blockade of ER stress and autophagy inhibited H2O2-induced cardiomyocyte apoptosis. ER stress activated autophagy through the PERK signalling in H2O2-treated H9C2 cells. Empagliflozin suppressed ER stress-induced autophagy by inhibiting the PERK/ATF4/Beclin1 signalling. H2O2 and I/R-induced cardiomyocyte apoptosis was restrained by empagliflozin through inhibition of ER stress-induced autophagy. Empagliflozin suppressed ER stress-induced autophagy via suppressing the PERK/ATF4/Beclin1 signalling, thus alleviating myocardial I/R injury and cardiomyocyte apoptosis.