Creatine kinase-MB Activity Research Articles

Anti-Protease Activity Deficient Secretory Leukocyte Protease Inhibitor (SLPI) Exerts Cardioprotective Effect against Myocardial Ischaemia/Reperfusion.

Inhibition of proteases shows therapeutic potential. Our previous studies demonstrated the cardioprotection by the Secretory Leukocyte Protease Inhibitor (SLPI) against myocardial ischaemia/reperfusion (I/R) injury. However, it is unclear whether the cardioprotective effect of SLPI seen in our previous works is due to the inhibition of protease enzymes. Several studies demonstrate that the anti-protease independent activity of SLPI could provide therapeutic benefits. Here, we show for the first time that recombinant protein of anti-protease deficient mutant SLPI (L72K, M73G, L74G) (mt-SLPI) could significantly reduce cell death and intracellular reactive oxygen species (ROS) production against an in vitro simulated I/R injury. Furthermore, post-ischaemic treatment of mt-SLPI is found to significantly reduce infarct size and cardiac biomarkers lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) activity, improve cardiac functions, attenuate I/R induced-p38 MAPK phosphorylation, and reduce apoptotic regulatory protein levels, including Bax, cleaved-Caspase-3 and total Capase-8, in rats subjected to an in vivo I/R injury. Additionally, the beneficial effect of mt-SLPI was not significantly different from the wildtype (wt-SLPI). In summary, SLPI could provide cardioprotection without anti-protease activity, which could be more clinically beneficial in terms of providing cardioprotection without interfering with basal serine protease activity.

Effect of Metformin on Myocardial Injury Induced by Hepatic Ischemia-Reperfusion in Rats.

Background: There is no effective medication for treatment or prevention of hepatic ischemia-reperfusion (HIR) injury caused by liver transplantation and hepatectomy. This study aimed to investigate the therapeutic effects of metformin on HIR injury and related myocardial injury in rats. Methods: Wistar male rats were randomly divided into four groups: sham group, ischemia-reperfusion group, and IR group treated with metformin 150 mg/kg and 100 mg/kg. Wistar male rats were administered metformin 150 mg/kg, 100 mg/kg or saline 30 min pre-operative and underwent 15 min ischemia and 6 h reperfusion (n = 4). Results: Metformin significantly alleviates the injury caused by HIR. Administration of metformin resulted in a significant reduction in the serum levels of alanine transaminase and aspartate transaminase and the activity of malondialdehyde, creatine kinase-MB, and lactate dehydrogenase but maintained high catalase and superoxide dismutase activity. Metformin significantly inhibited the IR-induced elevation of tumor necrosis factor-α in liver and heart tissue. Conclusion: Metformin can alleviate hepatic and myocardial injury induced by IR by inhibiting oxidative stress.

Ameliorative effect of flavonoid-rich extracts from Gongronema latifolium against diabetic cardiomyopathy via serpin A3 and socs3-a in streptozocin treated rats

Introduction The present study access the effect of the flavonoid-rich extract from Gongronema latifolium against cardiomyopathy streptozotocin-induced diabetic rats. Materials and methods The flavonoid-rich extract from G. latifolium leaf (FREGL) was prepared using a standard method. Diabetes was induced by a single intraperitoneal (i.p.) injection of streptozotocin. The experimental animals were divided into five groups as non-diabetic rats, diabetic control, diabetic rats administered low and high doses of FREGL (13 and 26 mg/kg), and metformin-glibenclamide orally for 21 days. Hence, the experimental animals were sacrificed; blood and heart were harvested to determine diverse biochemical parameters, including the gene expressions of serpin A3 and socs3-a as well as histological examination. Results The results demonstrated that FREGL significantly (p < 0.05) reduced fasting blood glucose, total cholesterol, low density lipoprotein (LDL), triglyceride (TG), lipid peroxidation levels, as well as the activities of lactate dehydrogenase and creatine kinase-MB, including the relative gene expressions of serpin A3 and Socs3-A in diabetic rats. Also, diabetic rats that received different doses of FREGL showed a substantial rise in insulin and high density lipoprotein (HDL) levels, antioxidant enzyme activities, as well as, normal histoarchitecture of the heart tissues. Conclusion Therefore, FREGL may be beneficial in alleviating diabetic cardiomyopathy.

The anti-ischemic and antioxidant activity of the pharmacological agonist of galanin receptor GalR2 and carnosine in in vitro and in vivo model systems

Antioxidant and anti-ischemic properties of the pharmacological agonist of galanin receptor GalR2 WTLNSAGYLLGPβAH (Gal) and its C-terminal fragment, dipeptide carnosine (βAH), were studied in the model of regional ischemia and reperfusion of the rat heart in vivo in the dose range of 0.5-5.0 mg/kg and Cu²⁺-induced free radical oxidation of low density lipoproteins (LDL) of human plasma in vitro for peptide concentrations of 0.01 mM and 0.1 mM. Gal was obtained by automatic solid phase synthesis using the Fmoc methodology; its structure was characterized by 1H-NMR spectroscopy and MALDI-TOF mass spectrometry. Intravenous administration of the optimal dose of Gal (1 mg/kg) to rats after ischemia was more effective than carnosine in reducing of the myocardial infarct size and the activity of creatine kinase-MB and lactate dehydrogenase in blood plasma at the end of reperfusion. It also improved the metabolic state of the reperfused myocardium and reduced the formation of peroxidation products during reperfusion. Gal reduced more effectively the formation of adducts of hydroxyl radicals in the interstitium of the area at risk (AAR) of the rat heart than carnosine. Carnosine at a dose of 1 mg/kg more effectively increased the activity of catalase and glutathione peroxidase in the AAR by the end of reperfusion compared to Gal. In a model of Cu²⁺-initiated oxidation of human plasma LDL 0.1 mM carnosine demonstrated a significantly more pronounced reduction in the formation of lipid radicals compared to Gal. The results show that Gal can be considered as a promising agent that reduces myocardial injury during reperfusion and oxidative stress.

Bioactive Extract of Morel Mushroom, Morchella esculenta (Ascomycota) Attenuates Doxorubicin-Induced Oxidative Stress Leading to Myocardial Injury.

Doxorubicin (DOX) is an extensively used anticancer drug for chemotherapy. Cardiotoxicity induced by DOX is an impediment in its clinical use. The aim of the current study is to evaluate the effect of a bioactive extract of an excellently edible morel mushroom, Morchella esculenta (ME) to attenuate DOX - induced cardiotoxicity. Protective effect of ME against DOX-induced cytotoxicity was evaluated in vitro by MTT assay using H9C2 cardiomyoblast cells. Intracellular free radical generation and mitochondrial membrane damage caused by DOX were detected by DCF-DA and rhodamine-123 dyes. Elevation of activities of creatine kinase-MB, lactate dehydrogenase and troponin I level consequent to the administration of DOX were determined using diagnostic kits. Depletion of endogenous antioxidant levels in myocardium was determined by spectrophotometric assays. Cardiac tissue damage caused by DOX was assessed by histopathological examination. ME reduced cytotoxicity caused by DOX at concentrations of 150 and 200 μg (p < 0.05 and p < 0.01, respectively). Cardiac injury marker levels elevated by DOX were significantly down regulated by ME (p < 0.01). Endogenous antioxidants such as SOD, GPx, and GSH depleted by DOX administration were restored to almost normal level by ME. This indicated the effect of ME to ameliorate oxidative stress caused by DOX administration leading to myocardial injury. Histopathological observation supported the finding. Being an excellently edible mushroom, current study indicates the potential therapeutic use of M. esculenta to prevent DOX-induced cardiotoxicity. The findings also suggest the clinical use of this medicinal mushroom to prevent chemo drug-induced cardiotoxicity.

Influence of Gender on Total Serum Creatine Kinase and Creatine Kinase-Mb Levels of Nigerian Hypertensives

Introduction: Hypertension is a long-term medical condition which when not detected and managed properly and on time often results to complications leading to disabilities and mortality. Gender has been known to affect the interpretation of some variables necessitating the need for gender-specific ranges.&#x0D; Objectives:This study evaluated total creatine kinase (CK) and creatine kinase-MB (CK-MB) isoenzyme activities of hypertensive subjects in Calabar, Nigeria and to assess if gender has influence on the activities of these enzymes.&#x0D; Methodology:One hundred and two participants were consecutively enrolled in this case control study. Serum total serum CK and CK-MB activity were evaluated in fifty one hypertensive and 51 normotensive subjects. The total CK levels were assessed using a spectrophotometric method while immunoinhibition method was used to determine the activity of CK-MB. Data was analyzed using Student’s t-test and Pearson’s correlation. Statistical significance was set at p&lt;0.05.&#x0D; Results:The total creatine kinase activities of the hypertensives did not differ significantly from those of the normotensive controls (p = 0.428) while the serum CK-MB activities of the hypertensive subjects were significantly higher than those of the normotensive controls (p=0.000). The body mass index of the hypertensives was significantly higher than those of the normotensive subjects (p=0.030). Gender had no effect on the blood pressure, body mass index and levels of CK and CK-MB (p&gt;0.05). There was also no significant correlation (p&gt;0.05) between blood pressure, body mass index and the levels of CK and CK-MB.&#x0D; Conclusion:CK-MB activities were significantly higher in hypertensive subjects compared to normotensive controls. There were no gender specific differences in the CK-MB levels of male and female hypertensives. This cardiac marker should be included in the routine assessment of hypertensives and gender-specific considerations may not be necessary in the interpretation of the data.

Vanillin modulates activities linked to dysmetabolism in psoas muscle of diabetic rats

Skeletal muscles are important in glucose metabolism and are affected in type 2 diabetes (T2D) and its complications. This study investigated the effect of vanillin on redox imbalance, cholinergic and purinergic dysfunction, and glucose-lipid dysmetabolism in muscles of rats with T2D. Male albino rats (Sprague–Dawley strain) were fed 10% fructose ad libitum for 2 weeks before intraperitoneally injecting them with 40 mg/kg streptozotocin to induce T2D. Low (150 mg/kg bodyweight (BW)) and high (300 mg/kg BW) doses of vanillin were orally administered to diabetic rats. Untreated diabetic rats and normal rats made up the diabetic control (DC) and normal control (NC) groups, respectively. The standard antidiabetic drug was metformin. The rats were humanely put to sleep after 5 weeks of treatment and their psoas muscles were harvested. There was suppression in the levels of glutathione, activities of SOD, catalase, ENTPDase, 5′Nucleotidase and glycogen levels on T2D induction. This was accompanied by concomitantly elevated levels of malondialdehyde, serum creatine kinase-MB, nitric oxide, acetylcholinesterase, ATPase, amylase, lipase, glucose-6-phosphatase (G6Pase), fructose-1,6-biphophastase (FBPase) and glycogen phosphorylase activities. T2D induction further resulted in the inactivation of fatty acid biosynthesis, glycerolipid metabolism, fatty acid elongation in mitochondria and fatty acid metabolism pathways. There were close to normal and significant reversals in these activities and levels, with concomitant reactivation of the deactivated pathways following treatment with vanillin, which compared favorably with the standard drug (metformin). Vanillin also significantly increased muscle glucose uptake ex vivo. The results suggest the therapeutic effect of vanillin against muscle dysmetabolism in T2D as portrayed by its ability to mitigate redox imbalance, inflammation, cholinergic and purinergic dysfunctions, while modulating glucose-lipid metabolic switch and maintaining muscle histology.

Spirulina platensis protects against microcystin-LR-induced toxicity in rats.

Microcystis aeruginosa produces an abundant cyanotoxin (microcystins (MCs) in freshwater supplies. MCs have adverse health hazards to animals and humans. Microcystin-leucine-arginine (microcystin-LR or MC-LR) is the most studied among these MCs due to their high toxicity. So, this study was designed to evaluate the possible therapeutic role of the natural algal food supplement, Spirulina platensis (SP), against MC-LR-induced toxic effects in male Wistar rats. Forty rats were randomly divided into five groups. Control and SP groups orally administered distilled water and SP (1000 mg/kg/daily), respectively, for 21 days. MC-LR group was intraperitoneally injected with MC-LR (10 μg/kg/day) for 14 days. MC-LR-SP500 and MC-LR-SP1000 groups were orally treated with SP (500 and 1000 mg/kg, respectively) for 7 days and concomitantly with MC-LR for 14 days. MC-LR induced oxidative hepatorenal damage, cardiotoxicity, and neurotoxicity greatly, which was represented by reduction of reduced glutathione content and the activities of glutathione peroxidase, catalase, and superoxide dismutase and elevation of concentrations of nitric oxide and malondialdehyde in renal, hepatic, brain, and heart tissues. In addition, it increased serum levels of urea, creatinine, tumor necrosis factor-alfa, interleukin-1beta and interleukin-6 and serum activities of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine kinase, and creatine kinase-MB. However, S. platensis restored normal levels of measured serum parameters, ameliorated MC-LR-induced oxidative damage, and normalized tissue antioxidant biomarkers. In conclusion, SP alleviated MC-induced organ toxicities by mitigating oxidative and nitrosative stress and lipid peroxidation.

Effect of 1-week Calendula officinalis consumption before high-intensity interval exercise on some delayed onset muscle soreness (DOMS) elements in male rowers

Previous studies showed that some medicinal herbs can prevent delayed onset muscle soreness (DOMS). The present study investigates the effect of Calendula officinalis supplementation on DOMS elements on male rowers. Thirty healthy adult male rowers were randomly chosen and equally divided into experimental and control groups. Blood samples, Sargent jumps (SJ), and pain perception tests were measured at the starting point. The experimental group consumed (twice a day, 200 μl each time) C. officinalis extract for a week while the control group received a placebo. After consuming the supplementations for a week, the second samples and tests were taken. All the athletes participated in the high-intensity interval exercise (HIIE – a muscle soreness protocol). Third, fourth, and fifth samples/tests were executed immediately, 24 and 48 h after HIIE. Statistical analysis was conducted and P≤0.05 was considered as the significant level. The results showed that HIIE induced a significant increase in the serum tumour necrosis factor-alpha (TNF-α) and creatine kinase-MB (CK-MB) values as well as the pain perception in both groups. TNF-α and pain perception were significantly lower in the experimental group immediately, 24 and 48 h after HIIE. CK-MB activity was significantly decreased in the experimental group during next 24 and 48 h after HIIE. The muscle soreness protocol and its preceding supplementation had no significant effect on SJ. The present study suggests that the consumption of C. officinalis based on the present study dose and timespan may be effective to attenuate inflammation and pain induced by HIIE in male rowers and probably has no functional impact on muscle.

Systemic implications of metallic foreign body syndrome in dairy cattle

This study aimed to evaluate the systemic implications of 37 cattle with traumatic reticulitis, evaluating clinical, laboratory, ultrasonographic and necroscopic changes. A clinical, laboratory and ultrasonographic examination was performed, and the animals were distributed in reticuloperitonitis (GI; n=21) and reticulopericarditis (GII; n=16) traumatic, based on necropsy findings. Blood samples were taken for haematological tests, serum total protein, albumin, globulin, gamma glutamyltransferase (GGT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), creatinine, urea, cortisol, creatine kinase (CK), creatine kinase-MB (CK-MB), cardiac troponin-I (cTn-I), plasma glucose and L-lactate. The abdominocentesis was productive in eight GI (n=8) and seven GII (n=7) animals, allowing the evaluation of physical, cytological and biochemical characteristics of the peritoneal fluid as a total protein, albumin, GLDH, AST, GGT, glucose and L-lactate. Changes in behavior, appetite, dehydration and temperature were observed, most expressive in GII. Hematology showed neutrophilic leukocytosis with regenerative left shift and hyperfibrinogenemia in both groups. Increased globulin, L-lactate concentration and serum GGT, GLDH, CK and CK-MB activity were observed, as well as significant elevation of cTnI (p=0.0190) in GII. In the peritoneal fluid exudate was observed in both groups and a higher concentration of L-lactate in relation to plasma. Ultrasound revealed retocular, cardiac, hepatic and splenic abnormalities. The anatomopathological lesions confirmed the ultrasound findings of both groups. The understanding of the syndrome helps in the diagnosis, as well as the adoption of preventive measures, minimizing the economic impact caused to the dairy cattle breeding.

Upregulation of FoxM1 protects against ischemia/reperfusion-induced myocardial injury.

Ischemia/reperfusion (I/R) induced lethal tissue injury in myocardium. FoxM1 (Forkhead Box M1), expressed in proliferating cardiac progenitor cells, could regulate myocardial development. However, the role of FoxM1 in I/R-induced myocardial injury has not been reported yet. Rats were conducted with regional ischemia followed by reperfusion in myocardium through ligation of the left anterior descending coronary artery. Triphenyl-tetrazolium chloride staining was utilized to assess the infarct size. ELISA was performed to detect activities of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH). Protein expression of FoxM1 in heart tissues and H9c2 were determined by western blot. H9c2 cells were used to establish a hypoxia/reoxygenation cell model, and the cell viability, proliferation and apoptosis were evaluated by MTT, EdU (5-ethynyl-2'-deoxyuridine) staining and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining, respectively. Adenovirus (Ad)-mediated over-expression of FoxM1 was injected into the anterior wall of the left ventricle of rats to evaluate the role of FoxM1 on in vivo I/R-induced myocardial injury. FoxM1 was reduced in heart tissues isolated from rats post myocardial I/R injury. Forced FoxM1 expression increased cell viability and proliferation of hypoxia/reoxygenation-induced H9c2, while repressed the cell apoptosis with increased Bcl-2 and decreased Bax and cleaved caspase-3. Injection of Ad-FoxM1 suppressed infarct size of the heart and decreased activities of CK-MB and LDH. FoxM1 attenuated I/R-induced myocardial injury, providing potential therapeutic target for the disease.

Upregulation of PCSK9, rho kinase and cardiac troponin by Eucalyptus globulus leaf extract improves fructose-streptozotocin-induced diabetic cardiac dysfunction in rats

Context The effect of Eucalyptus globulus in diabetic cardiac dysfunction and the possible mechanisms involved have not been explored. Objective To evaluate the effect of ethanol leaf extract of E. globulus (NEE) on the cardiac function of fructose/streptozotocin-induced diabetic rats. Materials and methods Type-2 diabetes was induced in rats with 10% fructose feeding for 14 days and an intraperitoneal administration of 40 mg/kg streptozotocin. Diabetic animals were treated with NEE (100–400 mg/kg) or 5 mg/kg glibenclamide orally for 21 days. Biochemical assays, histopathological examination and analyses of PCSK9, Rho kinase and Cardiac troponin expression were performed. Results The untreated diabetic group showed decreased expression of the genes, oxidative stress, dyslipidemia, increased activities of creatine kinase MB and lactate dehydrogenase, reduced nitric oxide level, and depletion of cardiomyocytes, which were reversed in NEE treated groups. Conclusions Eucalyptus globulus ameliorated diabetic cardiac dysfunction through increased PCSK9, Rho kinase and Cardiac troponin expression.

Electroacupuncture Pretreatment Mitigates Myocardial Ischemia/Reperfusion Injury via XBP1/GRP78/Akt Pathway.

Myocardial ischemia/reperfusion injury is a common clinical problem and can result in severe cardiac dysfunction. Previous studies have demonstrated the protection of electroacupuncture against myocardial ischemia/reperfusion injury. However, the role of X-box binding protein I (XBP1) signaling pathway in the protection of electroacupuncture was still elusive. Thus, we designed this study and demonstrated that electroacupuncture significantly improved cardiac function during myocardial ischemia/reperfusion injury and reduced cardiac infarct size. Electroacupuncture treatment further inhibited cardiac injury manifested by the decrease of the activities of serum lactate dehydrogenase and creatine kinase-MB. The results also revealed that electroacupuncture elevated the expressions of XBP1, glucose-regulated protein 78 (GRP78), Akt, and Bcl-2 and decreased the Bax and cleaved Caspase 3 expressions. By using the inhibitor of XBP1 in vitro, the results revealed that suppression of XBP1 expression could markedly increase the activities of lactate dehydrogenase and creatine kinase-MB and cell apoptosis, thus exacerbating stimulated ischemia/reperfusion-induced H9c2 cell injury. Compared with stimulated ischemia/reperfusion group, inhibition of XBP1 inhibited the downstream GRP78 and Akt expressions during stimulated ischemia/reperfusion injury. Collectively, our data demonstrated that electroacupuncture treatment activated XBP1/GRP78/Akt signaling to protect hearts from myocardial ischemia/reperfusion injury. These findings revealed the underlying mechanisms of electroacupuncture protection against myocardial ischemia/reperfusion injury and may provide novel therapeutic targets for the clinical treatment of myocardial ischemia/reperfusion injury.

Post-Ischemic Treatment of Recombinant Human Secretory Leukocyte Protease Inhibitor (rhSLPI) Reduced Myocardial Ischemia/Reperfusion Injury.

Myocardial ischemia/reperfusion (I/R) injury is a major cause of mortality and morbidity worldwide. Among factors contributing to I/R injury, proteolytic enzymes could also cause cellular injury, expand the injured area and induce inflammation, which then lead to cardiac dysfunction. Therefore, protease inhibition seems to provide therapeutic benefits. Previous studies showed the cardioprotective effect of secretory leukocyte protease inhibitor (SLPI) against myocardial I/R injury. However, the effect of a post-ischemic treatment with SLPI in an in vivo I/R model has never been investigated. In the present study, recombinant human (rh) SLPI (rhSLPI) was systemically injected during coronary artery occlusion or at the onset of reperfusion. The results show that post-ischemic treatment with rhSLPI could significantly reduce infarct size, Lactate Dehydrogenase (LDH) and Creatine kinase-MB (CK-MB) activity, inflammatory cytokines and protein carbonyl levels, as well as improving cardiac function. The cardioprotective effect of rhSLPI is associated with the attenuation of p38 MAPK phosphorylation, Bax, caspase-3 and -8 protein levels and enhancement of pro-survival kinase Akt and ERK1/2 phosphorylation. In summary, this is the first report showing the cardioprotective effects against myocardial I/R injury of post-ischemic treatments with rhSLPI in vivo. Thus, these results suggest that SLPI could be used as a novel therapeutic strategy to reduce myocardial I/R injury.

Effect of Methanol Extract of Baobab (Adansonia digitata L.) Fruit Pulp on NG-Nitro-L-Arginine Methyl Ester (L-NAME) Induced Hypertension in Rats.

Most available drugs used for management of hypertension have presented a plethora of challenges which genuinely called for development of therapies from natural sources. This study investigated the effect of methanol extract of Adansonia digitata fruit (MEADF) pulp on NG-nitro-L-arginine methyl ester (L-NAME) induced hypertension in rats. Fourty eight (48) wistar rats divided into six (6) groups (eight rats each) were employed. The induction of hypertension was achieved using L-NAME (40mg//kg body weight) by oral gavages. The induced rats were treated with MEADF pulp (200 and 400 mg/kg body weight) and Ramipril (10 mg/kg) and the remaining three groups serve as control. Serum haemodynamic and biochemical modifiable parameters were determined using standard assay procedures RESULTS: Administration of MEADF to the rats exerted a dose-dependent lowering effect on the elevated systolic blood pressure, diastolic blood pressure, mean arterial pressure and heart rate towards the normal physiological threshold. At 400 mg/kg of MEADF, there was significant (p < 0.05) reduction in serum lipid profile and biomarkers associated with endothelial dysfunction [angiotensin converting enzyme (ACE) activity], inflammation (C-reactive protein and interleukin-1β), oxidative stress (malondialdehyde) and cardiac injury (creatine kinase-MB and lactate dehydrogenase activities). However, serum concentrations of nitric oxide, high density lipoprotein cholesterol, total bilirubin and albumin were not significantly (p < 0.05) different from those found in normal control group. This study therefore demonstrates that MEADF possesses an in vivo ACE inhibitory activity, hypotensive potential and the ability to avert further degeneration of biochemical and physiological upsets associated with L-NAME induced hypertension.

Cardioprotective and Hepatoprotective Activity of Silymarin in BroilerChickens Fed on Mash and Pellet Diets

BACKGROUND: The liver and heart are two main damaged organs in ascites syndrome in fast -growing broilers. Using silymarin with a protective effect on the liver and heart may be a beneficial strategy to decrease ascites-induced mortality. OBJECTIVES: The present study assessed the cardiohepatic effects of silymarin in broilers fed on mash and pellet diets by assessing electrocardiographic (ECG) indices and some serum biochemical parameters. METHODS: A total of 120 Arbor Acres chicks were allocated to 6 groups and treated as follows: basal mash diet (CM); basal pellet diet (CP); silymarin at 500 ppm of mash (M500) and pellet diets (P500); and silymarin at 2500 ppm of mash (M2500) and pellet diets (P2500). RESULTS: CP had higher serum activities of aspartate aminotransferase, alanine aminotransferase, and creatine kinase MB (CK-MB) enzymes compared to CM (p <0.05). P2500 had a higher total protein and lower aspartate aminotransferase, alanine aminotransferase, and CK-MB compared to CP (p <0.05). T-duration, ST-segment, and R-R intervals were longer in CP compared to CM and were shorter in P2500 than in CP and P500 (p <0.05). CONCLUSIONS: The pellet diet led to changes in some biochemical and ECG indices in broilers, and silymarin at the 2500 ppm dose can be used as a hepatoprotective and cardioprotective compound to modulate cardiohepatic failure in susceptible broilers.

Modulatory activities of polyphenols on crude acetylene-induced cardiac and hepatic dysfunctions in a rat model

Exposure to crude acetylene can occur in occupational settings. This study assessed the modulatory activities of selected polyphenols on the hematotoxic, cardiotoxic, and hepatotoxic effects of crude acetylene. Wistar rats were exposed to 58 000 ppm crude acetylene for 10 min at 12 h intervals for 30 days. Some exposed groups were treated with 50 mg/kg rutin, quercetin, gallic acid, or tannic acid. Indices of hematological disorder, oxidative stress, and cardiovascular and hepatocellular injuries were evaluated in animals. The results showed a decrease in the levels of hematological indices in crude acetylene-exposed animals except for white blood cell count which was increased. Decreased activity/level of reduced glutathione, superoxide dismutase and ferric reducing antioxidant power with increased lipid peroxidation was observed in animals exposed to crude acetylene. Activities of transaminases, γ-glutamyl transpeptidase, and level of bilirubin were increased while the plasma albumin level was decreased. Dyslipidemia, increased activities of lactate dehydrogenase and creatine kinase-MB, and severe histopathological damage to hepatic and cardiac tissues were also observed in animals exposed to the gas. These deleterious hematological, biochemical, and histopathological changes were ameliorated in crude acetylene–toxified rats treated with the polyphenols. Tannic acid exhibited better activity than gallic acid while quercetin showed a superior activity to rutin. The results indicate that exposure to crude acetylene can lead to blood, heart, and liver-related diseases and dietary polyphenols could provide protective benefits.

Puerarin protects against myocardial ischemia/reperfusion injury by inhibiting inflammation and the NLRP3 inflammasome: The role of the SIRT1/NF-κB pathway

AimsThe purpose of this study was to investigate the protective effects of puerarin and elucidate the underlying mechanisms of puerarin in myocardial ischemia/reperfusion (MI/R) injury. Main methodsC57BL/6 mice were exposed to puerarin (100 mg/kg) with or without the SIRT1 inhibitor nicotinamide (500 mg/kg) and then subjected to MI/R operation. Myocardial infarct size, serum creatine kinase-MB (CK-MB) activity, apoptotic cell death, and cardiac structure and function were examined to evaluate MI/R injury. RT-PCR and western blotting were used to determine the inflammatory response and inflammasome activation, as well as activation of SIRT1/NF-κB pathway. ResultsPuerarin significantly reduced myocardial infarct size, serum CK-MB activity, and apoptotic cell death, and improved cardiac structural damage and dysfunction. Moreover, puerarin notably decreased the mRNA and protein levels of TNF-α, IL-6, and IL-1β, indicating that puerarin attenuated MI/R-induced inflammation. Furthermore, puerarin markedly decreased the protein levels of Ac-NF-κB, NLRP3, cleaved caspase-1, cleaved IL-1β, and cleaved IL-18 and increased the protein level of SIRT1. More importantly, the SIRT1 inhibitor nicotinamide prevented these puerarin-induced cardioprotective effects and regulation of the SIRT1/NF-κB pathway, as well as the NLRP3 inflammasome activation. ConclusionPuerarin protected against MI/R injury by inhibiting inflammatory responses probably via the SIRT1/NF-κB pathway, and inhibition of the NLRP3 inflammasome was also involved in puerarin-induced cardioprotective effects. These results suggest that puerarin may be a novel candidate for the treatment of ischemic heart disease.

Value of heart rate variability on dynamic electrocardiogram in predicting ventricular fibrillation in elderly acute myocardial infarction patients.

Ventricular fibrillation (VF) is the main cause of sudden death in Acute myocardial infarction (AMI) patients. Identifying arrhythmia as early as possible is of great significance in improving prognosis of AMI patients. The article is aimed at exploring the predictive value of heart rate variability (HRV) of dynamic electrocardiogram (DCG) in VF of elderly AMI patients. A total of 122 elderly AMI patients were enrolled as the research objects. They were divided into VF group and simple AMI group (AMI group). All underwent DCG test after admission. The basic data of patients were compared. HRV of DCG was observed. The predictive value of HRV of DCG in VF of elderly AMI patients was evaluated by receiver operating characteristic (ROC) curves. The ratio of Killip at grade II-III, activity of creatine kinase-MB (CK-MB), standard deviation of all R-R intervals (SDNN), the standard deviation of the R-R intervals (SDANN), root-mean-square of the successive differences of normal RR intervals (rMSSD) and percentage of NN50 in the total number of NN intervals PNN50 (PNN50%)]in VF group were higher than those in AMI group (P<0.05). The area under the ROC curves (AUC)and cut-off values of SDNN, SDANN, rMSSD and PNN50% were (0.773, 0.761, 0.800, 0.819) and (135.675, 106.850, 33.570, 14.080), respectively. HRV of DCG is of certain predictive value for VF in the elderly with AMI, which is expected to be an auxiliary diagnosis method of VF.

Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China.

The epidemiologic and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19) have been reported, but information on immune features associated with disease severity is scarce. To delineate and compare the immunologic features of mild and moderate COVID-19 in pediatric patients. This single-center case series included 157 pediatric patients admitted to Wuhan Children's Hospital with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were collected from January 25 to April 18, 2020. Documented SARS-CoV-2 infection. Clinical and immunologic characteristics were collected and analyzed. Outcomes were observed until April 18, 2020. Of the 157 pediatric patients with COVID-19, 60 (38.2%) had mild clinical type with pneumonia, 88 (56.1%) had moderate cases, 6 (3.8%) had severe cases, and 3 (1.9%) were critically ill. The 148 children with mild or moderate disease had a median (interquartile range [IQR]) age of 84 (18-123) months, and 88 (59.5%) were girls. The most common laboratory abnormalities were increased levels of alanine aminotransferase (ALT) (median [IQR], 16.0 [12.0-26.0] U/L), aspartate aminotransferase (AST) (median [IQR], 30.0 [23.0-41.8] U/L), creatine kinase MB (CK-MB) activity (median [IQR], 24.0 [18.0-34.0] U/L), and lactate dehydrogenase (LDH) (median [IQR], 243.0 [203.0-297.0] U/L), which are associated with liver and myocardial injury. Compared with mild cases, levels of inflammatory cytokines including interleukin 6, tumor necrosis factor α, and interferon γ were unchanged, whereas the level of immune suppressive interleukin 10 was markedly increased in moderate cases compared with mild cases (median [IQR], 3.96 [3.34-5.29] pg/mL vs 3.58 [3.10-4.36] pg/mL; P = .048). There was no statistically significant difference in absolute number of lymphocytes (including T cells and B cells) between mild and moderate cases, but moderate cases were associated with a decrease in neutrophil levels compared with mild cases (median [IQR], 2310/μL [1680/μL-3510/μL] vs 3120/μL [2040/μL-4170/μL]; P = .01). Immunoglobin G and the neutrophil to lymphocyte ratio were negatively associated with biochemical indices related to liver and myocardial injury (immunoglobulin G, ALT: r, -0.3579; AST: r, -0.5280; CK-MB activity: r, -0.4786; LDH: r, -0.4984; and neutrophil to lymphocyte ratio, ALT: r, -0.1893; AST: r, -0.3912; CK-MB activity: r, -0.3428; LDH: r, -0.3234), while counts of lymphocytes, CD4+ T cells, and interleukin 10 showed positive associations (lymphocytes, ALT: r, 0.2055; AST: r, 0.3615; CK-MB activity: r, 0.338; LDH: r, 0.3309; CD4+ T cells, AST: r, 0.4701; CK-MB activity: r, 0.4151; LDH: r, 0.4418; interleukin 10, ALT: r, 0.2595; AST: r, 0.3386; CK-MB activity: r, 0.3948; LDH: r, 0.3794). In this case series, systemic inflammation rarely occurred in pediatric patients with COVID-19, in contrast with the lymphopenia and aggravated inflammatory responses frequently observed in adults with COVID-19. Gaining a deeper understanding of the role of neutrophils, CD4+ T cells, and B cells in the pathogenesis of SARS-CoV-2 infection could be important for the clinical management of COVID-19.