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1.
J Photochem Photobiol B ; 202: 111705, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31812087

RESUMO

The procurance of gold nanoparticles in the plant extracts is an excellent way to attain nanomaterials natural and eco-friendly nanomaterials. The Dehydrated roots of Chinese Euphorbia fischeriana flowering plant are called "Lang-Du". In this study, the retrieving of gold nanoparticles from Euphorbia fischeriana root was amalgamated by standard procedure. Fabricated gold nanoparticles were portrayed through the investigations of ultraviolet and visible spectrophotometry (UV-Vis), Fourier transform infrared spectroscopy (FTIR), High resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD). The UV-Vis and FTIR results explicated the obtained particles were sphere-shaped and the terpenoids of Euphorbia fischeriana had strong communications with gold surface. The HRTEM and XRD images exposed the produced gold nanoparticles had an extreme composition of crystal arrangement and excellent uniformed size of particles. In our study, the Isoprenaline induced myocardial damage established the elevation in TBARS, LOOH of heart tissues and notable decline in antioxidant enzymes SOD, CAT, GPx, and GSH. This biochemical result was additionally proved by histopathological assessment. Remarkably, the pretreatment with EF-AuNps(50 mg/kg b.w) illustrated stabilized levels of serum creatine and cardiotropins in myocardial infarcted animals. And further we understood the essential function of NF-ƙB, TNF-α, IL-6 signaling molecules and its way progression in the development of vascular tenderness.


Assuntos
Euphorbia/química , Ouro/química , Nanopartículas Metálicas/uso terapêutico , Infarto do Miocárdio/prevenção & controle , Animais , Antioxidantes/química , Catalase/genética , Catalase/metabolismo , Creatina Quinase/sangue , Citocinas/metabolismo , Euphorbia/metabolismo , Química Verde , Isoproterenol/toxicidade , Nanopartículas Metálicas/química , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Extratos Vegetais/química , Raízes de Plantas/química , Ratos , ATPase Trocadora de Sódio-Potássio/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
2.
Life Sci ; 241: 117155, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31837330

RESUMO

AIMS: ß-Adrenoceptors (ß-ADRs) mediating the relaxation of rat superior mesenteric arteries (SMAs) were pharmacologically identified, and the effects of chemical sympathetic denervation on ß-ADR-mediated relaxation were examined. MAIN METHODS: The tension changes of endothelium-denuded SMAs were isometrically recorded and the mRNA of endothelium-denuded SMA ß-ADR was detected using RT-PCR. KEY FINDINGS: In endothelium-denuded SMAs contracted with ≥10-7 M phenylephrine (an α1-ADR agonist), isoprenaline (a ß-ADR agonist)-induced relaxation was competitively inhibited by 3 × 10-9-10-8 M propranolol (a ß1,2-ADR antagonist), but not further affected by ≥10-8 M propranolol. Although isoprenaline-induced relaxation was not affected by ICI-118,551 (10-9-10-8 M; a ß2-ADR antagonist), it was competitively inhibited by atenolol (10-7-3 × 10-7 M; a ß1-ADR antagonist) in the presence of ICI-118,551. In the presence of 10-7 M propranolol, isoprenaline- and CGP-12177A (a ß3-ADR partial agonist)-induced relaxation was competitively inhibited by high concentrations of bupranolol (a ß1,2,3-ADR antagonist), with pA2 values of 6.49 and 5.76, respectively. We detected the mRNA of ß1- and ß3-ADRs in endothelium-denuded SMAs. Treatment with 6-hydroxydopamine (a catecholaminergic neurotoxin) reduced maximal isoprenaline-induced relaxation in the presence and absence of 10-7 M propranolol, but not CGP-12177A-induced relaxation. SIGNIFICANCE: Isoprenaline-induced relaxation of rat SMAs is mediated by ß1- and ß3-ADRs. ß-ADR-mediated relaxation of rat SMAs is shown to be attenuated by chemical sympathetic denervation. The differences in the effects of bupranolol and chemical sympathetic denervation on the responses to isoprenaline and CGP-12177A in rat SMAs might be explained by the possible presence of multiple ß3-ADRs with different pharmacological properties.


Assuntos
Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Artéria Mesentérica Superior/fisiologia , Relaxamento Muscular/fisiologia , Receptores Adrenérgicos beta/química , Receptores Adrenérgicos beta/metabolismo , Simpatectomia Química/métodos , Animais , Isoproterenol/farmacologia , Masculino , Artéria Mesentérica Superior/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Propanolaminas/farmacologia , Ratos , Ratos Wistar
3.
Int J Nanomedicine ; 14: 8345-8360, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695371

RESUMO

Background: The protective role of puerarin (PUE) against myocardial infarction is closely related to its regulation on mitochondria. However, free PUE can hardly reach the mitochondria of ischemic cardiomyocytes due to the lack of mitochondrial targeting of PUE. Here PUE was loaded into mitochondria-targeted micelles (PUE@TPP/PEG-PE) for precisely delivering PUE into mitochondria with the aim of enhancing the anti-apoptosis effect. Methods: The mitochondriotropic polymer TPP-PEG-PE was synthesized for the preparation of PUE@TPP/PEG-PE micelles modified with triphenylphosphonium (TPP) cation. The physicochemical properties and anti-apoptosis effect of PUE@TPP/PEG-PE micelles were investigated. The coumarin 6 (C6)-labeled TPP/PEG-PE (C6@TPP/PEG-PE) micelles were used to observe the enhanced cellular uptake, mitochondrial targeting and lysosomes escape. Moreover, in vivo and ex vivo biodistribution of lipophilic near-infrared dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR)-labeled PUE@TPP/PEG-PE (DiR@TPP/PEG-PE) micelles were detected through fluorescence imaging. Results: The successful synthesis of TPP-PEG-PE conjugate was confirmed. PUE@TPP/PEG-PE micelles had a particle size of 17.1 nm, a zeta potential of -6.2 mV, and a sustained-release behavior. The in vitro results showed that the intracellular uptake of C6@TPP/PEG-PE micelles was significantly enhanced in H9c2 cells. C6@TPP/PEG-PE micelles could deliver C6 to mitochondria and reduce the capture of lysosomes. In addition, compared with the PUE@PEG-PE micelles and free PUE, the PUE@TPP/PEG-PE micelles exerted an enhanced protective effect against isoprenaline-induced H9c2 cell apoptosis, as evident by the decreased percentage of apoptotic cells, Caspase-3 activity, ROS level, Bax expression, and increased Bcl-2 expression. The in vivo detecting results of the targeting effect using DiR probe also indicated that TPP/PEG-PE micelles could accumulate and retain in the ischemic myocardium. Conclusion: The results of this study demonstrate the promising potential of applying PUE@TPP/PEG-PE micelles in mitochondria-targeted drug delivery to achieve maximum therapeutic effects of PUE.


Assuntos
Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Isoflavonas/farmacologia , Micelas , Mitocôndrias/metabolismo , Miócitos Cardíacos/patologia , Fosfinas/química , Animais , Cátions , Linhagem Celular , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Isoproterenol , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Ratos , Eletricidade Estática , Distribuição Tecidual/efeitos dos fármacos
4.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(10): 1049-1054, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31642443

RESUMO

OBJECTIVE: To study the changes and significance of apoptosis signal-regulating kinase 1 (ASK1) in left ventricular remodeling in FVB/N mice. METHODS: A total of 54 FVB/N mice were randomly divided into 4 groups: 0 d group with 8 mice, 7 d group with 10 mice, 14 d group with 16 mice, and 21 d group with 20 mice. A model of cardiac remodeling was established by intraperitoneal injection of isoproterenol (ISO) at a daily dose of 30 mg/kg, and the 7 d, 14 d, and 21 d groups were injected for 7, 14, and 21 consecutive days respectively. The 0 d group was given intraperitoneal injection of an equal volume of normal saline. Echocardiography was used to measure left ventricular posterior wall thickness at end diastole (dLVPW) and the ratio of heart weight to tibia length (HW/TL) was measured. Hematoxylin-eosin staining was used to measure left ventricular myocardial fiber diameter. Picric-Sirius red staining was used to measure myocardial collagen deposition area in the left ventricle. Quantitative real-time PCR was used to measure the mRNA expression of ASK1, type I collagen (collagen I), and B-type natriuretic peptide (BNP). The mortality rate was observed for each group. RESULTS: There were gradual increases in HW/TL, myocardial fiber diameter, and dLVPW after 0, 7, and 14 days of ISO injection (P<0.05). There were no significant changes in HW/TL ratio and dLVPW from days 14 to 21 of ISO injection (P>0.05), while there was a significant reduction in myocardial fiber diameter (P<0.05), which was similar to the value on day 7 (P>0.05). There were significant increases in myocardial collagen deposition area and the mRNA expression of collagen I, ASK1, and BNP after 0, 7, 14, and 21 days of ISO injection, which reached the peaks on day 21 (P<0.01). The mRNA expression of ASK1 was positively correlated with myocardial collagen deposition area and the mRNA expression of collagen I and BNP and had a weak correlation with HW/TL, myocardial fiber diameter, and dLVPW. There was a significant increase in the mortality rate of the mice over the time of ISO injection. CONCLUSIONS: The expression of ASK1 in the myocardium is closely associated with left ventricular remodeling. The increase of ASK1 expression may lead to the aggravation of left ventricular remodeling, and the mechanism of which needs further study.


Assuntos
Remodelação Ventricular , Animais , Isoproterenol , MAP Quinase Quinase Quinase 5 , Camundongos , Miocárdio , Miócitos Cardíacos
5.
Int Heart J ; 60(5): 1176-1183, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564708

RESUMO

Recently, the potential role of gut microbiome (GM) in cardiovascular diseases has been revealed. Heart failure (HF) is one of the most prevalent cardiovascular diseases worldwide; however, whether GM dysbiosis participates in the development of HF remains largely unknown. This study aimed to investigate the specific changes in GM composition and function in isoproterenol (ISO)-induced HF in rats.The rats were divided into C (control), 4w-HF (ISO, 2.5 mg/kg/day for 4 weeks, intraperitoneally), and 2w-HF (ISO, 2.5 mg/kg/day for 2 weeks, intraperitoneally) groups. The cardiac structure and function in rats were assessed, and metagenomic analyses were then performed. Compared with the healthy control group, we found that the Shannon diversity index and microbial gene count in the 4w-HF and 2w-HF groups was drastically decreased. High-throughput sequencing showed that the three groups differed in intestinal bacterial community composition. Overgrowth of bacteria, such as Prevotella, was observed in the 4w-HF group, with reduced growth of bacteria, such as Roseburia, Lactobacillus, and Butyrivibrio, associated with healthy status compared with the C group on the genus level. Concomitant with the alteration of GM composition, underrepresentation of health-linked microbial function was observed in both the 4w-HF and 2w-HF groups compared with the C group.Iso-induced HF rats showed a significant decrease in the diversity and richness of the intestinal microbiome, with a downregulation of the key intestinal bacterial groups and overgrowth of bacteria considered to be involved in inflammatory responses as well as a decrease in health-linked microbial function. Our data indicated that altered GM may be a potential player in the pathogenesis and progression of HF.


Assuntos
Bactérias/classificação , Microbioma Gastrointestinal/efeitos dos fármacos , Insuficiência Cardíaca/microbiologia , Isoproterenol/efeitos adversos , Metagenômica/métodos , Animais , Bactérias/genética , Modelos Animais de Doenças , Ecocardiografia , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/diagnóstico por imagem , Sequenciamento de Nucleotídeos em Larga Escala , Injeções Intraperitoneais , Isoproterenol/farmacologia , Masculino , Filogenia , Ratos , Análise de Sequência de DNA
6.
Am J Health Syst Pharm ; 76(8): 551-553, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-31420984

RESUMO

PURPOSE: A cost-reduction strategy for isoproterenol use in radiofrequency catheter ablation procedures was evaluated. SUMMARY: A medication-use evaluation at a 454-bed tertiary medical center revealed that the cardiac catheterization laboratory was the highest user of isoproterenol. Isoproterenol was removed from all AcuDose-Rx machines Omnicell, Mountain View, CA, and compounding was performed by pharmacy personnel. It was initially provided to the cardiac catheterization laboratory as an 8-µg/mL concentration in 20-mL 0.9% sodium chloride injection syringes with a 24-hour beyond-use date. This resulted in an initial cost savings but with an unacceptably high rate of wastage. Isoproterenol was then compounded as a 4-µg/mL concentration in 30 mL 5% dextrose in water syringes with a 9-day beyond-use date after a thorough literature search supported longer stability with this admixture. After 12 months of our current process, isoproterenol use during radio frequency catheter ablations (RFCAs) in the cardiac catheterization laboratory was reduced by 85%, decreasing the number of ampules used from 11.15 to 1.66 per week. CONCLUSION: A pharmacy-initiated process to mitigate an extraordinary increase in isoproterenol acquisition cost resulted in a reduction in usage in a tertiary care community hospital. Isoproterenol usage was reduced 85% after two different interventions were implemented, which is estimated to save $1,839 per procedure.


Assuntos
Ablação por Cateter/métodos , Redução de Custos , Composição de Medicamentos/métodos , Isoproterenol/economia , Serviço de Farmácia Hospitalar/economia , Ablação por Cateter/economia , Ablação por Cateter/instrumentação , Composição de Medicamentos/economia , Custos de Medicamentos/estatística & dados numéricos , Estabilidade de Medicamentos , Armazenamento de Medicamentos/economia , Registros Eletrônicos de Saúde/estatística & dados numéricos , Custos Hospitalares/estatística & dados numéricos , Humanos , Isoproterenol/administração & dosagem , Estudos Retrospectivos , Centros de Atenção Terciária/economia , Centros de Atenção Terciária/estatística & dados numéricos , Fatores de Tempo
7.
Molecules ; 24(15)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374848

RESUMO

Curcumin from Curcuma longa is a nutraceutical compound reported to possess strong antioxidant activity that makes it a candidate for use in counteracting oxidative stress-induced damage. The effect of pre-treatment with curcumin nanoparticles (nC) compared to conventional curcumin (Cs) on blood pressure, electrocardiogram, and biological changes on isoproterenol (ISO)-induced myocardial infarction (MI) in rats had been investigated. The Cs doses of 150 and 200 mg/kg bw and all nC doses (100, 150 and 200 mg/kg bw) significantly reduced heart rate before ISO administration and prevented QRS complex enlargement after MI induction (p < 0.026). All doses of Cs and nC prevented prolongation of the QT and QT corrected (QTc) intervals, with better results for higher doses (p < 0.048). The nC solution had more significant results than Cs in all metabolic parameters assessed (lactate dehydrogenase, glycaemia, aspartate transaminase, and alanine transaminase, p < 0.009). nC was more efficient than Cs in limiting myocardial oxidative stress and enhancing antioxidative capacity (p < 0.004). Compared to Cs, nC better prevented myocardial damage extension, reduced interstitial oedema, and inflammation. Curcumin nanoparticles as compared to conventional curcumin exert better antioxidative effects. Moreover, nC better prevent cardiomyocytes damage, and electrocardiogram alterations, in the case of ISO-induced MI in rats.


Assuntos
Curcumina/farmacologia , Coração/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Nanopartículas/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Cardiotônicos/química , Cardiotônicos/farmacologia , Curcuma/química , Curcumina/química , Modelos Animais de Doenças , Glutationa/química , Coração/fisiopatologia , Humanos , Isoproterenol/toxicidade , Infarto do Miocárdio/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos
9.
Hypertension ; 74(2): 295-304, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31291149

RESUMO

Subendocardial damage is among the first cardiac manifestations of hypertension and is already present in asymptomatic disease states. Accordingly, markers of subendocardial impairment may facilitate early detection of cardiac damages and risk stratification under these conditions. This study aimed to investigate the impact of subendocardial damage on myocardial microstructure and function to elucidate early pathophysiologic processes and to identify corresponding diagnostic measures. Mice (n=38) were injected with isoproterenol to induce isolated subendocardial scarring or saline as corresponding control. Cardiac function and myocardial deformation were determined by high-frequency echocardiography. The cardiac stress response was assessed in a graded exercise test and during dobutamine stress echocardiography. Myocardial microstructure was studied ex vivo by 7 T diffusion tensor magnetic resonance imaging at a spatial resolution of 100×100×100 µm 3 . Results were correlated with histology and biomarker expression. Subendocardial fibrosis was accompanied by diastolic dysfunction, impaired longitudinal deformation (global peak longitudinal strain [LS]: -12.5±0.5% versus -15.6±0.5%; P<0.001) and elevated biomarker expression (ANP [atrial natriuretic peptide], Galectin-3, and ST2). Systolic function and cardiac stress response remained preserved. Diffusion tensor magnetic resonance imaging revealed a left-shift in helix angle towards lower values in isoproterenol-treated animals, which was mainly determined by subepicardial myofibers (mean helix angle: 2.2±0.8° versus 5.9±1.0°; P<0.01). Longitudinal strain and subepicardial helix angle were highly predictive for subendocardial fibrosis (sensitivity, 82%-92% and specificity, 89%-90%). The results indicate that circumscribed subendocardial damage alone can cause several hallmarks observed in cardiovascular high-risk patients. Microstructural remodeling under these conditions involves also remote regions, and corresponding changes in longitudinal strain and helix angle might serve as diagnostic markers.


Assuntos
Endocárdio/patologia , Interpretação de Imagem Assistida por Computador , Isoproterenol/efeitos adversos , Imagem Cinética por Ressonância Magnética/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Animais , Biópsia por Agulha , Modelos Animais de Doenças , Ecocardiografia/métodos , Endocárdio/diagnóstico por imagem , Endocárdio/lesões , Fibrose/diagnóstico por imagem , Fibrose/patologia , Alemanha , Humanos , Imuno-Histoquímica , Injeções Subcutâneas , Isoproterenol/administração & dosagem , Modelos Lineares , Camundongos , Camundongos Endogâmicos , Curva ROC , Distribuição Aleatória , Valores de Referência , Volume Sistólico/fisiologia , Análise de Sobrevida , Disfunção Ventricular Esquerda/patologia
10.
Anticancer Res ; 39(7): 3519-3529, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262876

RESUMO

BACKGROUND/AIM: Although adrenergic agonists have been used in dental treatments and oral surgery for general anesthesia, their cytotoxicity against human oral malignant and non-malignant cell has not been well- understood. The present study was undertaken to investigate the cytotoxicity of five adrenergic agonists against human oral squamous cell carcinoma (OSCC), glioblastoma, promyelocytic leukemia, and normal oral mesenchymal cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast) and normal epidermal keratinocytes. MATERIALS AND METHODS: Tumor-specificity (TS) was calculated by the ratio between the mean 50% cytotoxic concentration against normal cells to that of tumor cells. Internucleosomal DNA fragmentation was detected using agarose gel electrophoresis. Caspase-3 activity was measured by substrate cleavage. RESULTS: Both cytotoxicity and tumor-specificity of adrenergic agonists against OSCC cell lines was in the order of isoprenaline>dexmedetomidine> adrenaline>clonidine and phenylephrine. Isoprenaline and dexmedetomidine did not induce apoptosis markers, such as internucleosomal DNA fragmentation and caspase-3 activation, but induced a smear pattern of DNA fragmentation in OSCC cell lines. Their cytotoxicity was not reduced by pretreatment with autophagy inhibitors, or by adrenoceptors antagonists. Addition of superoxide dismutase and catalase significantly reduced the cytotoxicity of isoprenaline, but not that of dexmedetomidine. CONCLUSION: Isoprenaline and dexmedetomidine induce non-apoptotic cell death by different mechanisms.


Assuntos
Agonistas Adrenérgicos/farmacologia , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Morte Celular/efeitos dos fármacos , Neoplasias Bucais/tratamento farmacológico , Catalase/farmacologia , Células Cultivadas , Criança , Clonidina/farmacologia , Fragmentação do DNA , Dexmedetomidina/farmacologia , Epinefrina/farmacologia , Humanos , Isoproterenol/farmacologia , Fenilefrina/farmacologia , Superóxido Dismutase/farmacologia
11.
Mar Drugs ; 17(7)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31288394

RESUMO

Cyanothece sp., a coccoid, unicellular, nitrogen-fixing and hydrogen-producing cyanobacterium, has been used in this study to biosynthesize customized gold nanoparticles under certain chemical conditions. The produced gold nanoparticles had a characteristic absorption band at 525-535 nm. Two types of gold nanoparticle, the purple and blue, were formed according to the chemical environment in which the cyanobacterium was grown. Dynamic light scattering was implemented to estimate the size of the purple and blue nanoparticles, which ranged from 80 ± 30 nm and 129 ± 40 nm in diameter, respectively. The highest scattering of laser light was recorded for the blue gold nanoparticles, which was possibly due to their larger size and higher concentration. The appearance of anodic and cathodic peaks in cyclic voltammetric scans of the blue gold nanoparticles reflected the oxidation into gold oxide, followed by the subsequent reduction into the nano metal state. The two produced forms of gold nanoparticles were used to treat isoproterenol-induced myocardial infarction in experimental rats. Both forms of nanoparticles ameliorated myocardial infarction injury, with a slight difference in their curative activity with the purple being more effective. Mechanisms that might explain the curative effect of these nanoparticles on the myocardial infarction were proposed. The morphological, physiological, and biochemical attributes of the Cyanothece sp. cyanobacterium were fundamental for the successful production of "tailored" nanoparticles, and complemented the chemical conditions for the differential biosynthesis process. The present research represents a novel approach to manipulate cyanobacterial cells towards the production of different-sized gold nanoparticles whose curative impacts vary accordingly. This is the first report on that type of manipulated gold nanoparticles biosynthesis which will hopefully open doors for further investigations and biotechnological applications.


Assuntos
Cianobactérias/química , Cyanothece/química , Ouro/química , Ouro/farmacologia , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Infarto do Miocárdio/tratamento farmacológico , Animais , Isoproterenol/química , Luz , Masculino , Miocárdio/química , Nitrogênio/química , Fixação de Nitrogênio/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
12.
Chem Biol Interact ; 308: 258-268, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31150630

RESUMO

The reactive oxygen species (ROS) induced oxidative stress is an inevitable factor for the pathogenesis of cardiovascular diseases. The edible marine algae-derived sulfated polysaccharides gained special attention as novel bioactive compounds having potential pharmacological activities. The present study evaluated in vitro and in vivo cardioprotective properties of sulfated polysaccharides from the edible brown marine algae Padina tetrastromatica (PSPS) against isoproterenol (ISO) induced cardiac damage. The cardioprotective properties of PSPS were first evaluated in H9c2 cardiac myoblasts and the results were confirmed by in vivo studies conducted in male Sprague-Dawley rats. The biochemical parameters, histopathological analysis, mRNA expressions, and ELISA studies indicated that PSPS significantly decreased (p < 0.05) the cardiac damage induced by ISO by reducing lipid peroxidation and improving antioxidant status, both in vitro and in vivo, via modulating PI3k/Akt/Nrf2 signaling pathway. The histopathological evidence further reinforced our findings and highlighted the promising cardioprotective activities offered by PSPS.


Assuntos
Isoproterenol/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Feófitas/metabolismo , Polissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Linhagem Celular , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Polissacarídeos/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Sulfatos/química
13.
Oxid Med Cell Longev ; 2019: 7847142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205590

RESUMO

Curcumin has anti-inflammatory, antioxidative, anticarcinogenic, and cardiovascular protective effects. Our study is aimed at evaluating the effects of pretreatment with curcumin nanoparticles (CCNP) compared to conventional curcumin (CC) on isoproterenol (ISO) induced myocardial infarction (MI) in rats. Fifty-six Wistar-Bratislava white rats were randomly divided into eight groups of seven rats each. Curcumin and curcumin nanoparticles were given by gavage in three different doses (100 mg/kg body weight (bw), 150 mg/kg bw, and 200 mg/kg bw) for 15 days. The MI was induced on day 13 using 100 mg/kg bw ISO administered twice, with the second dose 24 h after the initial dose. The blood samples were taken 24 h after the last dose of ISO. The antioxidant, anti-inflammatory, and cardioprotective effects were evaluated in all groups. All doses of CC and CCNP offered a cardioprotective effect by preventing creatine kinase-MB leakage from cardiomyocytes, with the best result for CCNP. All the oxidative stress parameters were significantly improved after CCNP compared to CC pretreatment. CCNP was more efficient than CC in limiting the increase in inflammatory cytokine levels (such as TNF-α, IL-6, IL-1α, IL-1ß, MCP-1, and RANTES) after MI. MMP-2 and MMP-9 levels decreased more after pretreatment with CCNP than with CC. CCNP better prevented myocardial necrosis and reduced interstitial edema and neutrophil infiltration than CC, on histopathological examination. Therefore, improving the bioactivity of curcumin by nanotechnology may help limit cardiac injury after myocardial infarction.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Curcumina/farmacologia , Isoproterenol/toxicidade , Infarto do Miocárdio/tratamento farmacológico , Nanopartículas/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Agonistas Adrenérgicos beta/toxicidade , Animais , Antioxidantes/farmacologia , Feminino , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/patologia , Nanopartículas/química , Ratos , Ratos Wistar
14.
Acta Cir Bras ; 34(5): e201900505, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31166461

RESUMO

PURPOSE: To evaluate the cardioprotective response of the pharmacological modulation of ß-adrenergic receptors (ß-AR) in animal model of cardiac ischemia and reperfusion (CIR), in spontaneously hypertensive (SHR) and normotensive (NWR) rats. METHODS: CIR was induced by the occlusion of left anterior descendent coronary artery (10 min) and reperfusion (75 min). The SHR was treated with ß-AR antagonist atenolol (AT, 10 mg/kg, IV) 5 min before CIR, and NWR were treated with ß-AR agonist isoproterenol (ISO, 0.5 mg/kg, IV) 5 min before CIR. RESULTS: The treatment with AT increased the incidence of VA, AVB and LET in SHR, suggesting that spontaneous cardioprotection in hypertensive animals was abolished by blockade of ß-AR. In contrast, the treatment with ISO significantly reduced the incidence of ventricular arrhythmia, atrioventricular blockade and lethality in NWR (30%, 20% and 20%, respectively), suggesting that the activation of ß-AR stimulate cardioprotection in normotensive animals. Serum CK-MB were higher in SHR/CIR and NWR/CIR compared to respective SHAM group (not altered by treatment with AT or ISO). CONCLUSION: The pharmacological modulation of ß-AR could be a new cardioprotective strategy for the therapy of myocardial dysfunctions induced by CIR related to cardiac surgery and cardiovascular diseases.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Agonistas Adrenérgicos beta/farmacologia , Atenolol/farmacologia , Cardiotônicos/farmacologia , Isoproterenol/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Receptores Adrenérgicos beta/efeitos dos fármacos , Animais , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Creatina Quinase Forma MB/sangue , Testes de Função Cardíaca , Masculino , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Ratos Endogâmicos SHR , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
15.
Can J Physiol Pharmacol ; 97(7): 661-674, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31157553

RESUMO

Diabetes increases the sensitivity of myocardium to ischemic damage and impairs response of the myocardium to cardioprotective interventions. The present study aimed to elucidate the potential cardioprotective effect provided by ranolazine during myocardial infarction in nondiabetic and diabetic male rats. As AMP-activated protein kinase (AMPK) has been shown to be involved in the cellular response to ischemic injury, in this context, the present animal study evaluated the modulating role of ranolazine in the AMPK expression in isoprenaline-induced myocardial ischemic rat model. Male rats were divided into 2 experiments: experiment I and II (nondiabetic and diabetic rats) and assigned to normal control, saline control for isoprenaline, isoprenaline control, and ranolazine-treated groups. Ranolazine administration revealed effectiveness in attenuating the severity of isoprenaline-induced myocardial injury in both nondiabetic and diabetic rats as revealed by ECG signs, histopathological score, and apoptotic markers via abrogating the increments in the inflammatory and oxidative stress markers and modulating AMPK expression. Therefore, the current cardioprotective effect of ranolazine was, at least in part, mediated through inhibition of apoptosis and modulation of AMPK expression, encouraging considering the utility of ranolazine in protection from acute myocardial infarction.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Diabetes Mellitus Experimental/complicações , Isoproterenol/efeitos adversos , Infarto do Miocárdio/patologia , Ranolazina/farmacologia , Doença Aguda , Animais , Glicemia/metabolismo , Eletrocardiografia , Hemoglobina A Glicada/metabolismo , Masculino , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
16.
Eur J Pharmacol ; 858: 172485, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31238067

RESUMO

Inhibiting Ca2+/calmodulin-dependent protein kinase II (CaMKII) over activation can decrease detrimental cardiac remodeling that leads to dilated cardiomyopathy, cell death, and heart failure. We previously showed that cellular retinoic acid binding protein 1 (Crabp1) knockout mice (CKO) exhibited a more severe isoproterenol (ISO)-induced heart failure and cardiac remodeling phenotype with elevated CaMKII activity in the heart, suggesting a cardiac-protective function of Crabp1 through modulating CaMKII activity. Here we examine whether the highly selective, endogenous ligand of Crabp1, all-trans retinoic acid (RA), can attenuate ISO-induced cardiac dysfunction. We also examine if this attenuation involves Crabp1 and the inhibition of CaMKII. RA pre-treatment followed by ISO challenge effectively restores ejection fraction in wild type, but not in CKO mice. This is correlated with reduced CaMKII auto-phosphorylation at T287 and phospholamban phosphorylation at T17, a substrate of CaMKII. RA pretreatment also reduces ISO-induced apoptosis in WT heart. Cell culture experiments confirm that RA inhibits CaMKII phosphorylation, which requires Crabp1. Molecular data reveal interaction of Crabp1 with the kinase and regulatory domains of CaMKII, and that RA selectively enhances Crabp1 interaction with the regulatory domain, suggesting a potential regulatory role for holo-Crabp1 in CaMKII activation. Together, these data demonstrate that RA bound Crabp1 plays a protective role in ß-adrenergic stimulated cardiac remodeling, which is partially attributed to its dampening CaMKII activation. Targeting Crabp1 provides a potentially new therapeutic strategy for managing heart diseases.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Coração/fisiopatologia , Isoproterenol/farmacologia , Receptores do Ácido Retinoico/metabolismo , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/química , Domínio Catalítico , Ativação Enzimática/efeitos dos fármacos , Coração/efeitos dos fármacos , Camundongos , Fosforilação/efeitos dos fármacos
17.
Pharmacol Rep ; 71(4): 682-687, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31201967

RESUMO

BACKGROUND: Myocardial injury (MI) is an important heart condition and a major cause of morbidity and mortality worldwide. The current study was designed to investigate the cardioprotective effects of cerebrolysin (CLY) on the lesion severity and inflammatory factors in male rats using isoproterenol (ISO)-induced MI model. METHODS: MI in rats was induced by injecting ISO (100 mg/kg) subcutaneously (sc) on the first 2 days. Then, CLY (5 ml/kg) was injected intraperitoneally (ip) post-treatment for 7 days. On the 3rd day, creatine phosphokinase (CK-MB) and cardiac troponin I (cTnI) levels in serum and, on the 10th day, the TNF-α and IL6 levels in serum and heart tissue were measured by enzyme-linked immunosorbent assay (ELISA). Finally, the heart of each rat was dissected out and stained for histopathological examination. RESULTS: On the 3rd day, the serum CK-MB and cTnI levels in the ISO and CLY + ISO groups were significantly increased compared with that in the control and CLY + Sal groups. One week after the induction of MI, ISO administration showed a significant increase in the serum level of TNF-α in the ISO group compared with that in the control and CLY + Sal groups. Also, our findings showed only a moderate reduction in inflammatory cell infiltration and extent of edema following CLY treatment in the CLY + ISO group. Also, CLY induced vascular proliferation in the heart tissue. CONCLUSIONS: We conclude that the severity of pathological changes induced by ISO in MI (e.g. inflammation and edema) can be limited by CLY treatment.


Assuntos
Aminoácidos/farmacologia , Cardiotônicos/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Miocárdio/patologia , Animais , Biomarcadores/sangue , Sobrevivência Celular/efeitos dos fármacos , Circulação Coronária/efeitos dos fármacos , Interleucina-6/metabolismo , Isoproterenol , Masculino , Células Musculares/efeitos dos fármacos , Células Musculares/patologia , Infarto do Miocárdio/sangue , Infarto do Miocárdio/imunologia , Miocárdio/metabolismo , Ratos Wistar , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue
18.
J Pharm Pharmacol ; 71(8): 1291-1300, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31215026

RESUMO

OBJECTIVES: To investigate the potential role and mechanism of TUPS, a soluble epoxide hydrolase inhibitor, in cardiac hypertrophy. METHODS: Rat and H9C2 cell models of cardiac hypertrophy were induced by isoproterenol and angiotensin II, respectively, followed by TUPS treatment. The expression of hypertrophic markers, ANP and BNP, was determined by quantitative real-time PCR. The abundance of Beclin-1, LC3, p-AMPK and phosphorylated-mammalian target of rapamycin (p-mTOR) proteins was analysed by Western blot and immunohistocytology. Cell morphology and viability were evaluated by F-actin staining and MTS. H9C2 cells were transfected with GFP-LC3 to evaluate autophagy flux. KEY FINDINGS: TUPS significantly inhibited rat heart size, heart weight-to-body weight ratio, heart wall thickness, hypertrophic H9C2 cell swelling and viability suppression as well as the expression of ANP and BNP genes in hypertrophic models. In addition, autophagic markers Beclin-1 and LC3 were elevated in both cellular and animal models, which were suppressed by TUPS, with corresponding changes of autophagy flux. The abundance of p-AMPK was increased, while p-mTOR was decreased in hypertrophic cells, which were abolished by TUPS. Rapamycin decreased p-mTOR level, increased Beclin-1 and LC3 expression and induced cell size enlargement and cell viability inhibition in hypertrophic H9C2 cells treated with TUPS. CONCLUSIONS: TUPS inhibits cardiac hypertrophy by regulating mTOR/autophagy axis.


Assuntos
Angiotensina II/farmacologia , Autofagia/efeitos dos fármacos , Cardiomegalia/induzido quimicamente , Cardiomegalia/tratamento farmacológico , Epóxido Hidrolases/antagonistas & inibidores , Isoproterenol/farmacologia , Pirenos/farmacologia , Animais , Proteína Beclina-1/metabolismo , Cardiomegalia/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ratos , Ratos Sprague-Dawley
19.
J Ethnopharmacol ; 242: 112037, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31247239

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: The leaves of Alpinia zerumbet is used in folk medicine in Brazil to treat hypertension. However, the cardioprotective effect of this plant has not been studied yet. AIM OF THIS STUDY: To evaluate the cardioprotective effects of the hydroalcoholic extract of the leaves of Alpinia zerumbet (AZE) against isoproterenol (ISO)-induced myocardial infarction in rats. MATERIAL AND METHODS: Rats were pretreated orally with AZE (300 mg/kg) for 30 days prior to ISO-induced myocardial infarction. The rats were sacrificed and hearts were collected and homogenized for biochemical analysis. At the end of the experiment, cardiac marker enzyme levels, histological and morphometric parameters, and hemodynamic measurements were assessed. Phytochemical compounds were verified by gas chromatography-mass spectrometry (GC-MS). RESULTS: Rats administered with ISO showed a significant increase in cardiac marker enzymes, i.e., in creatine kinase-NAC (CK-NAC) and CK-MB. Triphenyltetrazolium chloride (TTC) staining exhibited an increase in infarct areas. In the animals treated with ISO induced a significant increase in heart rate. Pretreatment with AZE significantly inhibited these effects of ISO. Moreover, biochemical findings were supported by histopathological observations. The GC-MS analyses of AZE identified volatile oils, kavalactones, and phytosterols. CONCLUSIONS: Haemodynamic, biochemical alteration and histopathological results suggest a cardioprotective protective effect of oral administration of AZE in isoproterenol induced cardiotoxicity.


Assuntos
Alpinia , Cardiotônicos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Pressão Sanguínea/efeitos dos fármacos , Creatina Quinase/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Isoproterenol , Masculino , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Folhas de Planta , Ratos Wistar
20.
Biosci Biotechnol Biochem ; 83(9): 1782-1789, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31045477

RESUMO

Activation of the adipose lipolytic pathway during lipid metabolism is mediated by protein kinase A (PKA), which responds to ß-adrenergic stimulation, leading to increased lipolysis. Soy is well known as a functional food and it is able to affect lipolysis in adipocytes. However, the mechanism by which soy components contribute to the lipolytic pathway remains to be fully elucidated. Here, we show that hydrolyzed soy enhances isoproterenol-stimulated lipolysis and activation of PKA in 3T3-L1 adipocytes. We also found that the expression of ß-adrenergic receptors, which coordinate the activation of PKA, is elevated in adipocytes differentiated in the presence of soy hydrolysate. The activity of the soy hydrolysate towards ß-adrenergic receptor expression was detected in its hydrophilic fraction. Our results suggest that the soy hydrolysate enhances the PKA pathway through the upregulation of ß-adrenergic receptor expression and thereby, increase lipolysis in adipocytes.


Assuntos
Adipócitos/metabolismo , Agonistas Adrenérgicos beta/farmacologia , Isoproterenol/farmacologia , Lipólise/efeitos dos fármacos , Receptores Adrenérgicos beta/metabolismo , Soja/metabolismo , Células 3T3-L1 , Animais , Cromatografia Líquida de Alta Pressão/métodos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Hidrólise , Camundongos
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