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.

A LAT1-Like Amino Acid Transporter Regulates Neuronal Activity in the Drosophila Mushroom Bodies.

The proper functioning of neural circuits that integrate sensory signals is essential for individual adaptation to an ever-changing environment. Many molecules can modulate neuronal activity, including neurotransmitters, receptors, and even amino acids. Here, we ask whether amino acid transporters expressed by neurons can influence neuronal activity. We found that minidiscs (mnd), which encodes a light chain of a heterodimeric amino acid transporter, is expressed in different cell types of the adult Drosophila brain: in mushroom body neurons (MBs) and in glial cells. Using live calcium imaging, we found that MND expressed in α/β MB neurons is essential for sensitivity to the L-amino acids: Leu, Ile, Asp, Glu, Lys, Thr, and Arg. We found that the Target Of Rapamycin (TOR) pathway but not the Glutamate Dehydrogenase (GDH) pathway is involved in the Leucine-dependent response of α/β MB neurons. This study strongly supports the key role of MND in regulating MB activity in response to amino acids.

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.

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.

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.

Inhibition of inducible nitric oxide synthase protects against the deleterious effects of sub-lethal sepsis and ethanol in the cardiorenal system.

We tested the hypothesis that ethanol would aggravate the deleterious effects of sub-lethal cecal ligation and puncture (SL-CLP) sepsis in the cardiorenal system and that inhibition of inducible nitric oxide synthase (iNOS) would prevent such response. Male C57BL/6 mice were treated with ethanol for 12weeks. One hour before SL-CLP surgery, mice were treated with N6-(1-iminoethyl)-lysine (L-NIL, 5mg/kg, i.p.), a selective inhibitor of iNOS. A second dose of L-NIL was administered 24h after SL-CLP surgery. Mice were killed 48h post surgery and the blood, the renal cortex, and the left ventricle (LV) were collected for biochemical analysis. L-NIL attenuated the increase in serum creatinine levels induced by ethanol, but not by SL-CLP. Ethanol, but not SL-CLP, increased creatine kinase (CK)-MB activity and L-NIL did not prevent this response. In the renal cortex, L-NIL prevented the redox imbalance induced by ethanol and SL-CLP. Inhibition of iNOS also decreased lipoperoxidation induced by ethanol and SL-CLP in the LV. L-NIL prevented the increase of pro-inflammatory cytokines and reactive oxygen species induced by ethanol and (or) SL-CLP in the cardiorenal system, suggesting that iNOS modulated some of the molecular mechanisms that underlie the deleterious effects of both conditions in the cardiorenal system.

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.

Novel g-C3N4/Fe-ZnO/RGO nanocomposites with boosting visible light photocatalytic activity for MB, Cr (VI), and outstanding catalytic activity toward para-nitrophenol reduction

A novel g-C3N4/Fe-ZnO/RGO nanocomposite has been synthesized using the facile solvothermal method to boost the catalytic efficiency of ZnO. The structure and morphology of nanocomposites were examined by a wide range of characterization methods. The obtained g-C3N4/Fe-ZnO/RGO nanocomposite (Z-scheme heterostructure) exhibits improved photocatalytic activity toward the photodegradation of MB, Cr (VI) under visible-light irradiation and 4-nitrophenol reduction. The enhancement in activity of nanocomposite is ascribed to a unique heterostructure system, which facilitates excellent transport and separation of the photogenerated charge carrier, resulting in prolonged lifetime leading to continuous generation of reactive species. Moreover, the synergistic effect on the interface of ZnO and g-C3N4 and the introduction of reduced graphene oxide (RGO) serve as a booster for charge separation at the Z-scheme, which ultimately speeds up the degradation of pollutants. The present study provides a novel and facile approach for establishing an efficient nanocomposite for environmental remediation.

Protective effect of puerarin against burn-induced heart injury in rats.

The present study evaluated the potential protective effects of puerarin and its associated mechanism on burn-induced myocardial damage. A total of 40 healthy adult Wistar rats were randomly divided into four groups: i) Sham; ii) burn; iii) burn + puerarin; and iv) puerarin. Serum levels of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and IL-6 were measured using ELISA. Myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were determined in myocardial homogenates using a commercial assay kit. TUNEL staining and western blot analysis of cleaved and pro-caspase-3 were also performed to assess apoptosis. Activation of p38-MAPK, ERK, JNK and AKT were measured using western blot analysis. Left ventricular systolic pressure, maximum rates of increase/decrease in left ventricular pressure, creatine kinase MB activity and cardiac troponin T levels were found to be altered in the burn group 12 h after burn, which were reversed by puerarin treatment. Injection of puerarin following burn injury also reduced heart water content. Serum levels of IL-1β, TNF-α and IL-6 were significantly higher in the burn group compared with those in the sham group. Puerarin treatment reduced serum levels of IL-1β, TNF-α and IL-6, in addition to reducing MPO activity and MDA levels in myocardial tissues. Puerarin inhibited the activation of caspase-3, p38, ERK and JNK following severe burn, but elevated Akt activation following severe burn. In conclusion, puerarin improved cardiac function in rats following severe burn injury, which may be due to reduced myocardial injury, inhibition of cardiomyocyte apoptosis and reduced oxidative inflammatory stress; the MAPK and AKT signaling pathways are proposed to the underlying mechanism of these findings.

Intravenous cannula can increase serum creatine kinase MB activity

Intravenous cannula can increase serum creatine kinase MB activity

Differential IL 10 serum production between an arm-based and a leg-based maximal resistance test

Bench press (i.e. arm-based) and half-squat (i.e. leg-based) are exercises commonly used to increase and evaluate muscular strength. In addition to differences in the location of the muscles that participate in each exercise, the total muscle mass required for the latter is larger than that involved in the former. The aim of this study is to analyze the effects of a maximal incremental strength test when performed by bench press and by half-squat on myocellular damage, oxidative damage and the inflammatory cytokine response. Ten male athletes were subjected to half-squat and bench press incremental strength tests. Blood samples were collected at rest, 15-minutes and 24 h post-test. Hydroperoxide and malondialdehyde concentrations were determined as lipid peroxidation markers. Lactate dehydrogenase (LDH) and creatine kinase isoenzyme MB (CK-MB) activities were determined as markers of muscle damage. α-Actin concentration was determined as a marker of sarcomeric damage. Serum interleukin (IL) 6, IL10, and tumor necrosis factor alpha (TNFα) were determined to assess the inflammatory response. LDH and CK-MB values were greater at 15 min and 24 h post bench press exercise (p < 0.05). No differences were found in lipid peroxidation or α-actin. Interestingly, IL10 values were greater in response to the press bench at 24 h post-test (p < 0.05). Our results suggest that, at equivalent workloads, an arm-based exercise induced higher anti-inflammatory effects and more severe muscle damage compared with a leg-based exercise.

Inhibiting MicroRNA-29a Protects Myocardial Ischemia-Reperfusion Injury by Targeting SIRT1 and Suppressing Oxidative Stress and NLRP3-Mediated Pyroptosis Pathway

To investigate the effects of microRNA-29a (miR-29a) on myocardial ischemia-reperfusion (I/R) injury and its specific mechanisms, we used H9C2 myocardial cells to establish a myocardial ischemia model by hypoxia/reoxygenation (H/R), and microRNA-29a inhibitor was interfered. Annexin V/propidium iodide and flow cytometry were used to detect the effects of cell death. C57 mice were used to establish were used to establish the I/R injury model, and H&E staining was used to detect pathologic damage to heart tissues. The expressions of miR-29a silent information regulator factor 2-related enzyme 1 (SIRT1) and nucleotide-binding oligomerization domain like receptor protein 3 (NLRP3), as well as pyroptosis-related proteins were determined by quantitative reverse-transcription polymerase chain reaction and Western blot analysis. The serum levels of 2-hydroxybutyrate dehydrogenase (HBDH), lactate dehydrogenase-1 (LDH), creatine kinase (CK), creatine kinase MB activity (CK-MB), IMA, and inflammatory factors in I/R rats were significantly up-regulated. In the I/R group, the expression of miR-29a was significantly up-regulated while SIRT1 was remarkably down-regulated. Dual luciferase reporter assay showed SIRT1 was a direct target of miR-29a. Inhibition of miR-29a significantly up-regulated the expression of peroxisome proliferator-activated receptor gamma coactivator-1α/nuclear respiratory factor-2 and endothelial nitric oxide synthase while remarkably down-regulating levels of inducible nitric oxide synthase and malondialdehyde in I/R. The oxidative stress that was induced by I/R injury was also suppressed by inhibition of miR-29a. All these effects of miR-29a inhibition were reversed by small interfering SIRT1. The in vitro H/R results showed that NLRP3-caspase-1-mediated pyroptosis was activated in H/R but was significantly inhibited by the inhibition of miR-29a. Inhibition of miR-29a improved myocardial I/R injury by targeting SIRT1 through suppressing oxidative stress and NLRP3-mediated pyroptosis. SIGNIFICANCE STATEMENT: In this study, we showed for the first time that miR-29a could improve myocardial I/R injury through inhibition of pyroptosis.

MicroRNA expression, targeting, release dynamics and early-warning biomarkers in acute cardiotoxicity induced by triptolide in rats

Tripterygium wilfordii Hook. F. is a plant used in traditional Chinese medicine to treat rheumatoid arthritis, lupus erythematosus, and psoriasis in China. However, its main active substance, triptolide, has toxic effects on the heart, liver, and kidneys, which limit its clinical application. Therefore, determining the mechanism of cardiotoxicity in triptolide and identifying effective early-warning biomarkers is beneficial for preventing irreversible myocardial injury. We observed changes in microRNAs and aryl hydrocarbon receptor (AhR) as potential biomarkers in triptolide-induced acute cardiotoxicity by using techniques such as polymerase chain reaction (PCR) assay. The results revealed that triptolide increased the heart/body ratio and caused myocardial fiber breakage, cardiomyocyte hypertrophy, increased cell gaps, and nuclear dissolution in treated male rats. Real-time PCR array detection revealed a more than 2-fold increase in the expression of 108 microRNA genes in the hearts of the male rats; this not only regulated the signaling pathways of ErbB, FOXO, AMPK, Hippo, HIF-1α, mTOR, and PI3K-Akt but also participated in biological processes such as cell adhesion, cell cycling, action potential, locomotory behavior, apoptosis, and DNA binding. Moreover, triptolide reduced the circulatory and cardiac levels of AhR protein as a target of these microRNAs and the messenger RNA expression of its downstream gene CYP1 A1. However, decreases in myocardial lactate dehydrogenase, creatine kinase MB, catalase, and glutathione peroxidase activity and an increase in circulating cardiac troponin I were observed only in male rats. Moreover, plasma microRNAs exhibited dynamic change. These results revealed that circulating microRNAs and AhR protein are potentially early-warning biomarkers for triptolide-induced cardiotoxicity.

Assessment of antiproliferative activity of Capparis spinosa L extract against Ehrlich ascites carcinoma in Swiss albino mice

Background: Medicinal plants have been known as one of the most important therapeutic agents for cancer treatment and prevention. Capparis spinosa L is a multipurpose plant that contains different bioactive phytochemicals including phenols and flavonoids.Aims: In the present study we explore the invivo anti-tumor activity of Capparis spinosa L extract and most potent constituents rutin and hesperidin against Ehrlich ascites carcinoma (EAC). Also study the side effect of treatments on different organs (liver, kidney and heart). Material and method: The antitumor effect was assessed by evaluating tumor volume , tumor cell count , survival time and increase in life span of EAC bearing mice. We assessed the effect of Capparis spinosa L extract , rutin and hesperidin on the level of malonaldialdhyde (MDA) and Catalase activity. Also, we estimated their effect on Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) , Albumin , urea , creatinine ,Lactate dehydrogenase activity (LDH), Creatine Kinase -MB activity (CK-MB). Apoptosis was assessed by BCL2 and caspase3 activity. Results : The Capparis spinosa L extract , rutin and hesperidin showed significantly decreased (p<0.001) in the volume of the EAC and in the count of EAC cells and increase the life span of EAC bearing mice. The treatment with Capparis spinosa L extract , rutin and hesperidin showed significantly decreased (p<0.001) the lipid peroxidation marker (MDA) and recovered catalase activity towards normal as compared to positive control. We founded that Capparis spinosa L extract , rutin and hesperidin treatment induced apoptosis demonstrated by an increased in Caspase 3 activity and decreased in BCL2 .The treatment of Capparis spinosa L extract , rutin and hesperidin significantly reduced the elevated levels of ALT , AST ,LDH ,CK-MB,Urea and Creatinine in positive control as compared with negative control. Also, they showed protection for both liver and kidney histopathologically. Conclusions: The present study demonstrated that Capparis spinosa L extract , rutin and hesperidin have potent antitumor activity against Ehrlich ascites carcinoma. The anti-tumor mechanism may be mediated by preventing oxidative damage and induction of apoptosis.

Prognostic Value of Serum Troponin T in Unstable Angina.

Abstract Background. Cardiac troponin T is a regulatory contractile protein not normally found in blood. Its detection in the circulation has been shown to be a sensitive and specific marker for myocardial cell damage. We used a newly developed enzyme immunoassay for troponin T to determine whether its presence in the serum of patients with unstable angina was a prognostic indicator. Methods. We screened 109 patients with unstable angina (25 with accelerated or subacute angina and 84 with acute angina at rest) for serum creatine kinase activity, creatine kinase isoenzyme MB activity, and troponin T every eight hours for two days after admission to the hospital. The outcomes of interest during the hospitalization were death and myocardial infarction. Results. Troponin T was detected (range, 0.20 to 3.64 μg per liter; mean, 0.78; median, 0.50) in the serum of 33 of the 84 patients (39 percent) with acute angina at rest. Only three of these patients had elevated creatine kinase MB activity (two were positive...

Ginkgo biloba extract prevents acute myocardial infarction and suppresses the inflammation‑ and apoptosis‑regulating p38 mitogen‑activated protein kinases, nuclear factor‑κB and B‑cell lymphoma 2 signaling pathways.

Ginkgobiloba is a plant known from the Mesozoic and has been regarded as one of the first to be used in traditional Chinese medicine (TCM). The plant extract has attracted a great deal of attention in recent years. The Ginkgobiloba leaf contains flavones and diterpenes. In addition, Ginkgobiloba performs certain pharmacologic actions, including antioxidant and anti‑aging activities. The aim of the present study was to examine whether Ginkgobiloba extract prevents acute myocardial infarction (AMI). The results demonstrated that Ginkgobiloba extract significantly inhibited infarct size, increased serum histamine levels and weakened creatine kinase (CK)‑MB activity in AMI mice. Ginkgobiloba extract significantly inhibited serum interleukin (IL)‑6 and IL‑1β levels, and caspase‑3/9 activity. In addition, it suppressed matrix metallopeptidase‑9, transforming growth factor‑β, p38 mitogen‑activated protein kinases (MAPK) and nuclear factor (NF)‑κB protein expression, and promoted B‑cell lymphoma2 (Bcl‑2) protein expression in AMI mice. The results of invivo assays demonstrated that Ginkgobiloba extract prevents AMI and suppresses inflammation‑ and apoptosis‑regulating p38 MAPK, NF‑κB and Bcl‑2 signaling pathways.

The oxidative stress and antioxidant therapy in patients with acute and chronic poisoning by pesticides

Anticholinesterase poisoning is an important health problem in developing countries, and understanding of its underlying mechanisms is essential for the effective treatment. This study is designed to examine the effects of Y-27632, a selective Rho-kinase inhibitor, on organophosphate-induced cardiac toxicity and mortality in rats. Rats were randomly divided into 4 groups: control (corn oil), dichlorvos (30 mg/kg intraperitoneally), and 1- and 10-mg/kg Y-27632 + dichlorvos groups. After 6 hours of intraperitoneal injection, venous blood and cardiac samples were obtained, biochemical or immunohistochemical analyses were performed, and the intensity of muscle fasciculation was recorded. Serum cholinesterase activities were suppressed with dichlorvos, and these reductions were inhibited with Y-27632 pretreatment. Serum creatine kinase, creatine kinase–MB activities, and myoglobin and N-terminal probrain natriuretic peptide concentrations were not markedly affected with poisoning or Y-27632. Although serum nitric oxide concentrations did not change with dichlorvos, cardiac nitric oxide levels were markedly increased with Y-27632 pretreatment. Cardiac glutathione levels also increased with 1 mg/kg Y-27632. There was no staining for apoptosis, and immunohistochemical analyses of inducible nitric oxide synthase showed no change in cardiac tissue for all of the groups. Both doses of Y-27632 abolished mortality in rats with acute dichlorvos exposure (100% survival). These results show that administration of Rho-kinase inhibitor can produce protective effects against dichlorvos intoxication in rats. These findings may provide new possibilities for the treatment of organophosphate poisoning.

Pentoxifylline abrogates cardiotoxicity induced by the administration of a single high dose or multiple low doses of doxorubicin in rats.

Doxorubicin (DOX) possesses a broad-spectrum antineoplastic activity; however, its clinical application is impeded by cardiotoxicity. This study aimed to investigate the protective effect of pentoxifylline (PXF), which possesses antioxidant and anti-inflammatory properties against cardiotoxicity induced by a single high dose (15 mg/kg, i.p.) or multiple low doses (2.5 mg/kg, i.p., three times per week for 2 weeks) of DOX. At the end of the experimental period, the serum creatine kinase (CK)-MB and lactate dehydrogenase (LDH) activities were measured. The hearts were then removed for evaluating TNF-α, NO, malondialdehyde (MDA), and reduced glutathione (GSH) levels, superoxide dismutase (SOD) and catalase (CAT) activities, and the expression of iNOS, NF-κB, Fas ligand (FasL), and caspase-3. The administration of DOX in both dose regimens caused increases in serum CK-MB and LDH activities, in cardiac TNF-α, NO and MDA levels, as well as in the cardiac expression of iNOS, NF-κB, FasL and caspase-3, whereas it significantly reduced the cardiac GSH level, as well as SOD and CAT activities (P < 0.05). Prophylactic treatment of rats with PXF diminished DOX-induced alterations in theses parameters. Our results warrant the clinical use of PXF as an adjuvant therapy to abrogate cardiotoxicity of DOX and extend its clinical applications.

Changes in heart rate, arrhythmia frequency, and cardiac biomarker values in horses during recovery after a long-distance endurance ride.

OBJECTIVE To evaluate heart rate, heart rate variability, and arrhythmia frequency as well as changes in cardiac biomarker values and their association with heart rate in horses before and after an endurance ride. DESIGN Cross-sectional study. ANIMALS 28 Arabian horses competing in a 120- or 160-km endurance ride. PROCEDURES ECG recordings were obtained from each horse before (preride) and after (recovery) an endurance ride to evaluate changes in heart rate and the SD of normal R-R intervals (SDNN) during the initial 12 hours of recovery. Frequencies of supraventricular and ventricular premature complexes before and after the ride were evaluated. Blood samples were obtained before the ride and twice during recovery. Hematologic analyses included measurement of serum cardiac troponin I concentration and creatine kinase isoenzyme MB activity. RESULTS Heart rate was significantly increased and SDNN was decreased during the recovery versus preride period. Frequency of ventricular premature complexes increased during recovery, albeit not significantly, whereas frequency of supraventricular premature complexes was not significantly different between preride and recovery periods. Serum cardiac troponin I concentration and creatine kinase isoenzyme MB activity were significantly increased in the recovery versus preride period. No associations were identified between cardiac biomarkers and velocity, distance, or mean heart rate. CONCLUSIONS AND CLINICAL RELEVANCE Heart rate increased and SDNN decreased in horses after completion of an endurance ride. These and other cardiac changes suggested that prolonged exercise such as endurance riding might have cardiac effects in horses. Additional studies are needed to clarify the clinical relevance of the findings.