المؤلفون: Fang Wang, Su Gao, Peng-Fei Wang, Yun-Dong Xie, Jin Wang, Xiao-Ping Wang, Li-Na Quan, Xiao-Ting Wang, Ya-Heng Wang, Ji-Qing Bai

المصدر: Biomedicine & Pharmacotherapy, Vol 118, Iss, Pp-(2019)

مصطلحات موضوعية: 0301 basic medicine, Male, Carthamustinctorius, Carthamus tinctorius, Myocardial Ischemia, Apoptosis, Salvia miltiorrhiza, Blood stasis, Pharmacology, Rats, Sprague-Dawley, chemistry.chemical_compound, 0302 clinical medicine, Creatine Kinase, MB Form, Myocytes, Cardiac, bcl-2-Associated X Protein, biology, General Medicine, 030220 oncology & carcinogenesis, medicine.symptom, Protective effects, Acute myocardial ischemia, Ischemia, Inflammation, RM1-950, Superoxide dismutase, 03 medical and health sciences, Troponin T, Lactate dehydrogenase, medicine, Animals, Aspartate Aminotransferases, L-Lactate Dehydrogenase, business.industry, Interleukin-6, Superoxide Dismutase, Tumor Necrosis Factor-alpha, Myocardium, Herb pair, Isoproterenol, Transcription Factor RelA, medicine.disease, 030104 developmental biology, chemistry, Hemorheology, biology.protein, Creatine kinase, Therapeutics. Pharmacology, business, Potential, Drugs, Chinese Herbal

الوصف: Danshen (salvia miltiorrhiza) and honghua(Carthamus tinctorius) were traditional herb pair with promoting blood circulation and removing blood stasis actions, in China. Both were widely used to treat cardiovascular diseases (CVD) for hundreds years, especially shown definite advantage in the treatment of ischemic heart disease (IHD). However, the mechanism of danshen-honghua herb pair (DHHP) in the treatment of IHD was still unclear. This study was focused on examining the effects and possible mechanisms of DHHP in rats with acute myocardial ischemia induced by isoproterenol (ISO). The results suggested that DHHP significantly ameliorated the myocardial tissue abnormalities, notablely inhibited the elevation of lactate dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST), creatinekinase isoenzyme (CK-MB) and cardiac troponin T (CTn-T) in plasma, obviously decreased the plasma levels of Tumor Necrosis Factor α (TNF-α), outstandingly inhibited the reduction of superoxide dismutase (SOD), catalase (CAT) caused by ISO, significantly inhibited the high expression of Bcl-2 assaciated X protein (Bax) and nuclear transcriptionfactor-κBP65 (NF-κBP65) protein, significantly induced the low expression of B-cell lymphoma-2 (Bcl-2) protein in acute myocardial ischemia rats. DHHP can obviously ameliorate hemodynamic parameters. In summary, DHHP can significantly improve myocardial ischemia in acute myocardial ischemia model rats caused by ISO. Anti-free radicals, anti-peroxidation, inhibition of cell apoptosis and anti- inflammation maybe are the potential mechanisms of DHHP anti-myocardial ischemia in acute myocardial ischemia rats in duced by ISO.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4005c1a9a0c3ce4785908697819ec63aTest
https://pubmed.ncbi.nlm.nih.gov/31545239Test

المؤلفون: Limei Zhou, Min Li, Xuwen Li, Yongri Jin

المصدر: Biomedicine & Pharmacotherapy, Vol 130, Iss, Pp 110538-(2020)

مصطلحات موضوعية: 0301 basic medicine, Male, Magnetic Resonance Spectroscopy, Ginsenosides, Platelet Aggregation, Blood viscosity, Myocardial Infarction, Panax, Myocardial Reperfusion Injury, RM1-950, Pharmacology, High-performance liquid chromatography, Superoxide dismutase, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Lactate dehydrogenase, medicine, Animals, Myocytes, Cardiac, Myocardial infarction, Oleanolic Acid, Rats, Wistar, Chromatography, High Pressure Liquid, chemistry.chemical_classification, biology, Chemistry, Glutathione peroxidase, Hemodynamics, General Medicine, Saponins, medicine.disease, Blood Viscosity, Rats, Panacis majoris Rhizoma, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Total saponins, Myocardial ischemia-reperfusion, Therapeutics. Pharmacology, Isosorbide dinitrate, Reperfusion injury, Degradation products, Rhizome, medicine.drug

الوصف: Ethnopharmacological relevance Panacis majoris Rhizoma, which is a member of herbal medicine, is known for many years to remove blood stasis, promote blood circulation, and enrich the blood. The active ingredients of this plant are mainly attributed to saponins. Aim of the study The total saponins from Panacis majoris Rhizoma (TSPJ), and the degradation products of TSPJ (DTSPJ), were designed in this study to compare the protective effects on myocardial ischemia-reperfusion injury, and the aim of this approach is to discover more effective agents for the treatment of ischemic heart diseases. We analyzed the main constituents of TSPJ and DTSPJ, aiming to make clear which saponins played important roles in this protective effect, and also investigated the possible mechanisms. Materials and methods DTSPJ was prepared by the method of alkaline hydrolysis. High performance liquid chromatography (HPLC) were used to analyze the main chemical constituents of TSPJ and DTSPJ, which were isolated by chromatographic techniques and identified by comparison with the Nuclear Magnetic Resonance (NMR) data in reported literature. Male Wistar rats were randomized to sham-operated group, ischemia-reperfusion group, three TSPJ (50, 100 and 200 mg/kg) groups, three DTSPJ (50, 100 and 200 mg/kg) groups, and isosorbide dinitrate tablet (5.0 mg/kg) group. The rats in all groups were intragastrically administrated once per day for three successive days. The establishment of the model of myocardial ischemia-reperfusion injury was used the following method: firstly, the left coronary artery of experimental rat was ligated for 30 min and then reperfused for 120 min. Then the myocardial infarct size, hemorheological and biochemical parameters, whole blood viscosity, plasma viscosity, platelet adhesion rate, platelet aggregation and histopathology changes were assessed. Results Five C3,C28-bidesmosidic oleanane-type saponins and ginsenoside Rd were the main constituents of TSPJ, and their total content in TSPJ was 79.2 %. The main constituents of DTSPJ were five C3-monodesmosidic oleanane-type saponins and ginsenoside Rd, and their total content in DTSPJ was 72.6 %. The HPLC analysis revealed that the five C3,C28-bidesmosidic oleanane-type saponins in TSPJ were completely turned into five C3-monodesmosidic oleanane-type saponins in DTSPJ through the method of alkaline hydrolysis, but ginsenoside Rd remained unchanged. Both TSPJ and DTSPJ could significantly reduced myocardial infarct size, and improved heart function, and lowered the activities of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase isoenzymes (CK-MB), and malonyldialdehyde (MDA) content, as well as the levels of whole blood viscosity, plasma viscosity, platelet adhesion rate, and platelet aggregation; on the contrary, both the level of glutathione peroxidase (GSH-Px) and the activity of superoxide dismutase (SOD) were notablely increased. The results of histopathological examination further supported the cardioprotective effects of TSPJ and DTSPJ. Conclusion Both TSPJ and DTSPJ can guard cardiomyocytes against myocardial ischemia-reperfusion injury. The underlying mechanisms may be closely related to its enhancing anti-oxidative properties, modifying blood viscosity, and inhibiting platelet aggregation and platelet adhesion. As a whole, the protection of DTSPJ against myocardial ischemia-reperfusion injury was a little stronger than those of TSPJ. The results display the prospect of DTSPJ as a drug candidate for treating ischemic heart disease.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::18483ecd3a3dda7090da89147cbb4fbfTest
https://pubmed.ncbi.nlm.nih.gov/32731133Test

المؤلفون: Lei Su, Yue Li, Xu Li, Xintao Zhu, Guozhen Wang, Huasheng Tong

المصدر: Biomedicine & Pharmacotherapy, Vol 129, Iss, Pp 110489-(2020)

مصطلحات موضوعية: 0301 basic medicine, Male, Proteomics, Programmed cell death, Necroptosis, Apoptosis, Heat stroke, RM1-950, Liver injury, Heat Stress Disorders, 03 medical and health sciences, chemistry.chemical_compound, Extracellular Vesicles, 0302 clinical medicine, Tandem Mass Spectrometry, Lactate dehydrogenase, medicine, Animals, Humans, Chromatography, High Pressure Liquid, Pharmacology, Chemistry, General Medicine, Hep G2 Cells, medicine.disease, Cell biology, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, iTRAQ, 030220 oncology & carcinogenesis, Hepatocyte, Proteome, Hepatocytes, Therapeutics. Pharmacology, Apoptosis Regulatory Proteins, Intracellular, Heat-Shock Response, Signal Transduction

الوصف: Liver injury is a common complication of severe heat stroke (HS). Extracellular vesicles (EVs) are part of a novel pathway mediating intercellular communication. Whether EVs are involved in the pathogenesis underlying HS-induced liver injury remains unknown. Here, we explored the role of hepatocyte EVs in HS-induced liver injury and their protein regulation patterns after HS induction. Isobaric tags for relative and absolute quantification technology (iTRAQ) and liquid chromatography-tandem mass spectrometry analysis identified changes in the proteomic profiles of hepatocyte-derived heat-stroked EVs, and we identified 53 up-regulated proteins. Bioinformatics analysis verified that the regulation of programmed cell death was the most significant altered pathway. To clarify the effect of HS hepatocyte-derived EVs in inducing hepatocyte-programmed death and injury, they were added to recipient hepatocytes and injected into mice. This treatment significantly induced the synthesis of apoptosis (caspase-3/8) and necroptosis-associated proteins [receptor-interacting protein 1 (RIP1), RIP3, and mixed lineage kinase domain-like protein]; moreover, it increased the numbers of apoptotic and necroptotic cells in hepatocytes and liver tissues and increased the levels of biochemical liver injury markers (alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase). Our study is the first comprehensive analysis of the hepatocyte-derived heat-stroked EV proteome confirming the induction of liver injury by Evs. We provide a novel explanation for the pathological mechanism underlying HS-induced liver injury.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::114f0bb76a5ace813e1aa3012fb94db1Test
https://pubmed.ncbi.nlm.nih.gov/32768969Test

المؤلفون: Tomal Dattaroy, Santanu Dasgupta, Vinod Nagle, Jayanta Talukdar, Bhaskar Bhadra

المصدر: Biomedicine & Pharmacotherapy, Vol 132, Iss, Pp 110886-(2020)
Biomedicine & Pharmacotherapy

مصطلحات موضوعية: 0301 basic medicine, ARDS, Exacerbation, MSCs, mesenchymal stem cells, MPO, myeloperoxidase, Review, ICAM-1, intercellular adhesion molecule-1, Xanthophylls, Cytokine storm, M-CSF, macrophage colony-stimulating factor, PDGF, platelet-derived growth factor, Pathogenesis, 0302 clinical medicine, Risk Factors, IkB, inhibitor nuclear factor-kappa B, GSH, glutathione, TGF, transforming growth factor, NT, nitrotyrosine, TNF, tumor necrosis factor, LDH, lactate dehydrogenase, Acute respiratory distress syndrome, IL-1ra, interleukin-1 receptor antagonist, General Medicine, VEGF, vascular endothelial growth factor, CCL-3, chemokine (C-C motif) ligand 3, 030220 oncology & carcinogenesis, COX-2, cyclooxygenase-2, CRP, C-reactive protein, LPS, lipopolysaccharide, Cytokines, Tumor necrosis factor alpha, dsRNA, double stranded ribonucleic acid, Antioxidant, GM-CSF, granulocyte-macrophage colony-stimulating factor, MIP, macrophage inflammatory protein, ALT, alanine transaminase, HCFs, human cardiac fibroblasts, HDAC4, histone deacetylase 4, RM1-950, Lung injury, Antiviral Agents, stat, 03 medical and health sciences, Immune system, Fibrinolytic Agents, SOD, superoxide dismutase, medicine, PGE2, prostaglandin E2, Animals, Humans, ComputingMethodologies_COMPUTERGRAPHICS, Pharmacology, MDA, malondialdehyde, NO, nitric oxide, business.industry, PPARs, peroxisome proliferator-activated receptors, SARS-CoV-2, Astaxanthin, COVID-19, MCP, monocyte chemoattractant protein, medicine.disease, G-CSF, granulocyte colony-stimulating factor, COVID-19 Drug Treatment, 030104 developmental biology, Immunology, FOXO3, forkhead box O3 gene, HGF, hepatocyte growth factor, MMPs, matrix metalloproteinases, HIF-1α, hypoxia inducible factor 1α, Therapeutics. Pharmacology, AST, aminotransferase, Anti-inflammatory, business, MAPK, mitogen-activated protein kinase, LFA-1, leukocyte function antigen 1

الوصف: Graphical abstract
Highlights • CS triggered by excessive inflammatory response drives the pathogenesis of COVID-19. • ASX inhibits TNFα, IL1β, IL6 via regulation of NF-kB & JAK/STAT; prevents CS & ALI/ARDS. • ASX suppresses plasma CRP, iNOS, COX2, PGE2 & ICAM-1; prevents oxidative damages. • ASX inhibits NLRP3, HIF1α, activates Nrf2, Sirtuin pathways; exerts antioxidant effect. • ASX enhances immune responses, NK cell activity, T- & B- cell population.
Host excessive inflammatory immune response to SARS-CoV-2 infection is thought to underpin the pathogenesis of COVID-19 associated severe pneumonitis and acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Once an immunological complication like cytokine storm occurs, anti-viral based monotherapy alone is not enough. Additional anti-inflammatory treatment is recommended. It must be noted that anti-inflammatory drugs such as JAK inhibitors, IL-6 inhibitors, TNF-α inhibitors, colchicine, etc., have been either suggested or are under trials for managing cytokine storm in COVID-19 infections. Natural astaxanthin (ASX) has a clinically proven safety profile and has antioxidant, anti-inflammatory, and immunomodulatory properties. There is evidence from preclinical studies that supports its preventive actions against ALI/ARDS. Moreover, ASX has a potent PPARs activity. Therefore, it is plausible to speculate that ASX could be considered as a potential adjunctive supplement. Here, we summarize the mounting evidence where ASX is shown to exert protective effect by regulating the expression of pro-inflammatory factors IL-1β, IL-6, IL-8 and TNF-α. We present reports where ASX is shown to prevent against oxidative damage and attenuate exacerbation of the inflammatory responses by regulating signaling pathways like NF-ĸB, NLRP3 and JAK/STAT. These evidences provide a rationale for considering natural astaxanthin as a therapeutic agent against inflammatory cytokine storm and associated risks in COVID-19 infection and this suggestion requires further validation with clinical studies.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8cd7bf3aa8d9fd5d6f23a47947a5470cTest
https://pubmed.ncbi.nlm.nih.gov/33113418Test

المؤلفون: Huihui Zhou, Miaoqin Wu, Yu Shen, Luyi Zhang

المصدر: Biomedicine & Pharmacotherapy, Vol 132, Iss, Pp 110790-(2020)

مصطلحات موضوعية: 0301 basic medicine, Adult, Indocyanine Green, Male, Cell viability, Cell Survival, Ependymoglial Cells, RM1-950, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, In vivo, Lactate dehydrogenase, Rosaniline Dyes, Humans, Viability assay, Cytotoxicity, Coloring Agents, Cells, Cultured, Pharmacology, Müller cells, Toxicity, General Medicine, Trypan Blue, Middle Aged, Cell counting, Molecular biology, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Trypan blue, Intraocular dyes, Female, Therapeutics. Pharmacology, Indocyanine green

الوصف: This study investigated the in vitro effect of various vital dyes in common clinical use on human Muller cell viability, and it compared the toxicity of these dyes using a cell culture model. Muller cells were exposed to a series of concentrations (1 %, 0.5 %, 0.25 %, and 0.125 % or 12.9 mM, 6.45 mM, 3.22 mM and 1.61 mM) of Indocyanine green (ICG) for 2, 24, 48, and 72 h. Similarly, groups of Muller cells were stained with "Heavy" brilliant blue G (HBBG), Trypan blue (TB) (0.15 %, or 1.56 mM), Membrane-blue-dual (MBD), and ICG (0.25 %, or 3.22 mM) or BBG (0.025 %, or 0.3 mM) with glucose (GS) (50 %, 66 % and 75 % or 2.78 M, 3.67 M and 4.17 M) for 30, 60, and 120 s. Cell viability was measured with the Cell Counting Kit-8 (CCK-8) and Lactate Dehydrogenase (LDH) release assays. We found that high stain concentration and long exposure time resulted in increased toxicity to Muller cells. Nevertheless, ICG seemed to be safe at the clinically relevant concentration of 0.25 % (3.22 mM) in the short time of exposure. TB was safer than both HBBG and MBD, especially HBBG. Hypertonic GS as a dilution was not safe for Muller cells, and the negative effect was more obvious in 0.025 % (0.3 mM) BBG than that in 0.25 % (3.22 mM) ICG. This is the first report to observe the cytotoxicity of commonly used stains in clinical on human Muller cells in vitro, and to provide some basis for further studies, including in vivo investigation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f0ae5a34dd40011e6c09430f0f517879Test
https://pubmed.ncbi.nlm.nih.gov/33035834Test

المؤلفون: Hong-Ru Zhang, Hua Bai, Liang Ding, Yi-Huang Gu, Yan Xiao, Wan-Ying Chen, Ze-Hao Zhong, Hao Chen, Sheng-Feng Lu

المصدر: Biomedicine & Pharmacotherapy, Vol 127, Iss, Pp 110148-(2020)

مصطلحات موضوعية: 0301 basic medicine, Male, Trimetazidine, Myocardial Infarction, Apoptosis, Myocardial Reperfusion Injury, mTORC1, RM1-950, Pharmacology, Mechanistic Target of Rapamycin Complex 1, Mitochondrial Proteins, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Reperfusion therapy, Adenosine Triphosphate, Troponin complex, Lactate dehydrogenase, Mitophagy, medicine, Animals, Autophagy-Related Protein-1 Homolog, Sirolimus, Ischemic cardiomyopathy, business.industry, Membrane Proteins, General Medicine, medicine.disease, mTORC1-ULK1-FUNDC1, Electroacupuncture preconditioning, Mitochondria, Rats, Disease Models, Animal, 030104 developmental biology, Electroacupuncture, chemistry, 030220 oncology & carcinogenesis, Myocardial ischemia-reperfusion injury, Therapeutics. Pharmacology, business, Reperfusion injury, medicine.drug

الوصف: Myocardial ischemia/reperfusion (I/R) is an important complication of reperfusion therapy for myocardial infarction, and trimetazidine is used successfully for treatment of ischemic cardiomyopathy by regulating mitochondrial function. Moreover, electroacupuncture (EA) preconditioning was demonstrated to be cardioprotective in both in vivo rodent models and in patients undergoing heart valve replacement surgery. However, the mechanisms have not been well elucidated. Mitophagy, mediated by the mTORC1-ULK1-FUNDC1 (mTOR complex 1-unc-51-like autophagy-activating kinase 1-FUN14 domain-containing 1) pathway, can regulate mitochondrial mass and cell survival effectively to restrain the development of myocardial ischemia/reperfusion injury (MIRI). In this study, we hypothesized that EA preconditioning ameliorated MIRI via mitophagy. To test this, rapamycin, an mTOR inhibitor, was used. The results showed that EA preconditioning could reduce the infarct size and risk size, and decrease the ventricular arrhythmia score and serum creatine kinase-myocardial band isoenzyme (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin T (cTnT) in MIRI rats. Moreover, it also attenuated MIRI-induced apoptosis and mitophagy accompanied by elevated mTORC1 level and decreased ULK1 and FUNDC1 levels. However, these effects of EA preconditioning were blocked by rapamycin, which aggravated MIRI, reduced adenosine triphosphate (ATP) production, and antagonized infarct size reduction. In conclusion, our results indicated that EA preconditioning protected the myocardium against I/R injury by inhibiting mitophagy mediated by the mTORC1-ULK1-FUNDC1 pathway.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a5042f7d594cf2510456fb963cafa1edTest
https://pubmed.ncbi.nlm.nih.gov/32344255Test

المؤلفون: Guangying Yuan, Zeliang Liu, Fang Li, Hao Wang, Qiong Lai, Boyang Yu, Junping Kou

المصدر: Biomedicine & Pharmacotherapy, Vol 124, Iss, Pp 109820-(2020)

مصطلحات موضوعية: 0301 basic medicine, Cardiac function curve, Purine, Male, Cardiotonic Agents, Molecular biology, Myocardial Infarction, Myocardial Ischemia, RM1-950, Pharmacology, Mechanism of action, 03 medical and health sciences, NT5E, chemistry.chemical_compound, Mice, 0302 clinical medicine, Lactate dehydrogenase, medicine, Animals, Metabolomics, Myocardial infarction, Metoprolol, Cardioprotection, Mice, Inbred ICR, biology, business.industry, General Medicine, medicine.disease, Disease Models, Animal, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, biology.protein, Creatine kinase, Therapeutics. Pharmacology, business, medicine.drug

الوصف: Metoprolol (Met) is widely applied in the treatment of myocardial infarction and coronary heart disease in clinic. However, the metabolic network in vivo affected by Met manipulation is still unclear and it's therapeutic molecular mechanisms were remained to be furthered elucidated except β1 adrenergic receptor. Myocardial infarction (MI) was induced by permanent CAL for 24 h in ICR mice. Myocardial infarct size, biochemical indicators such as creatine kinase (CK), lactate dehydrogenase (LDH), C-reactive Protein (CRP), tumor necrosis factor-α (TNF-α) and cardiac troponin I(cTn-I), cardiac function and myocardial pathological changes were detected to ensure the improvement of Met on MI. Subsequently, the significantly changed endogenous metabolites and the network in both serum and urine were screened and constructed through metabolomics by using HPLC-Q-TOF/MS. Finally, the potential regulatory enzymes that could be the possible new therapeutic targets of Met were selected and validated by western blotting and immunohistochemistry based on the screened differential metabolites and the enrichment analysis. Met effectively reduced the infarct size of myocardial infarction mice, improved the biochemical indicators, and ameliorated the cardiac function and pathological conditions. Our study further found that Met could regulate the pathways of glycine, serine and threonine metabolism, cysteine and methionine metabolism, purine and pyrimidine metabolism under the pathological conditions of MI. Moreover, several regulatory enzymes involved GATM, CSE and NT5E were demonstrated to be regulated by Met. This study constructed the regulatory metabolic network map of Met, elucidated the endogenous metabolic pathway regulated by Met, and validated the new potential therapeutic targets of Met in MI, which might provide a further reference for the clinical application of Met.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::347144ebb9bf70a616d802c64be07098Test
https://pubmed.ncbi.nlm.nih.gov/31972362Test

المؤلفون: Leila Zeidooni, Mohammad Rashno, Tuba Alibakhshi, Layasadat Khorsandi, Mohammad Javad Khodayar

المصدر: Biomedicinepharmacotherapy = Biomedecinepharmacotherapie. 105

مصطلحات موضوعية: 0301 basic medicine, Zingerone, Male, Side effect, Pharmacology, medicine.disease_cause, Kidney, Protective Agents, Nephrotoxicity, Blood Urea Nitrogen, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Lactate dehydrogenase, Malondialdehyde, Medicine, Animals, Rats, Wistar, Serum Albumin, Cisplatin, Inflammation, Creatinine, L-Lactate Dehydrogenase, business.industry, Tumor Necrosis Factor-alpha, Body Weight, Guaiacol, Neurotoxicity, General Medicine, Organ Size, medicine.disease, Glutathione, Oxidative Stress, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, business, Oxidative stress, medicine.drug

الوصف: Cisplatin is one of the most commonly used and highly effective cancer chemotherapeutic agents. Use of cisplatin is limited due to persistence of severe side effects such as nephrotoxicity, neurotoxicity, and hearing loss. Nephrotoxicity is the most common limiting side effect of cisplatin use. Zingerone is one of the active ingredients present in ginger plant that has anti-inflammatory and antioxidant effects. In this study, Wistar rats were assigned randomly to 6 groups with 5 animals in each group. The control group; cisplatin group which received 7.5 mg/kg of cisplatin intraperitoneally (i.p.) at the 4th day; zingerone group received 50 mg/kg of zingerone orally for 7 days. Three other groups were pretreated with 10, 20, and 50 mg/kg of zingerone orally for 7 days and cisplatin administered 7.5 mg/kg i.p. at the 4th day, respectively. The animals were sacrificed 72 h after cisplatin injection and blood samples were taken to evaluate the serum factors. Right kidneys were collected for histopathological studies and left kidneys were considered to measure the oxidative stress parameters and TNF-α cytokine. Co-administration of zingerone along with cisplatin resulted a statistically significant reduction in lactate dehydrogenase (LDH) activity, creatinine and BUN levels of serum in comparison with cisplatin alone group (P 0.01). Zingerone significantly decreased the tissue levels of malondialdehyde (MDA) (P 0.05) and significantly retained the enzyme activity of catalase (CAT) (P 0.05) and glutathione peroxidase (GPX) (P 0.05) in kidney tissue compared to cisplatin. Zingerone did not permit the reduction of glutathione (GSH) levels (P 0.001) in kidney tissue and by reducing the level of tumor necrosis factor (TNF)-α (P 0.05) suppressed the inflammation produced by cisplatin. Furthermore, zingerone improved histopathological changes such as vacuolation (fat deposit), brush border loss, infiltration of leukocytes, glomerular diameters and congestion of RBCs. However, our findings suggest that zingerone has nephroprotective effects in cisplatin rat model of nephrotoxicity mostly through suppression of oxidative stress and inflammation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9c290e0ff8f04e85e4426cca5e1222dbTest
https://pubmed.ncbi.nlm.nih.gov/29857302Test

المؤلفون: Sanjiu Yu, Jihang Zhang, Chuan Liu, Jie Yu, Jie Yang, Laiping Zhang, Shizhu Bian, Chen Zhang, Shiyong Yu, Lan Huang

المصدر: Biomedicine & Pharmacotherapy, Vol 116, Iss, Pp 109003-(2019)

مصطلحات موضوعية: 0301 basic medicine, Cardiac function curve, medicine.medical_specialty, Adolescent, Systole, Trimetazidine, Physical exercise, RM1-950, Altitude Sickness, Placebo, Ventricular Function, Left, Placebos, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Double-Blind Method, Internal medicine, High altitude, Medicine, Humans, Fatigue, Pharmacology, Ejection fraction, L-Lactate Dehydrogenase, business.industry, Incidence (epidemiology), Altitude, Incidence, Myocardium, Cardiac function, Cardiorespiratory fitness, General Medicine, Clinical trial, 030104 developmental biology, Cardiorespiratory Fitness, 030220 oncology & carcinogenesis, Heart Function Tests, Cardiology, Lactates, Regression Analysis, Therapeutics. Pharmacology, business, Energy Metabolism, medicine.drug

الوصف: Trimetazidine (TMZ) has been shown to optimize myocardial energy metabolism and is a common anti-ischemic agent. Our trial (ChiCTR-TRC-13003298) aimed to explore whether TMZ has any preventive effect on high-altitude fatigue (HAF), cardiac function and cardiorespiratory fitness upon acute high-altitude exposure and how it works on HAF. Thirty-nine healthy young subjects were enrolled in a randomized double-blinded placebo-controlled trial and were randomized to take oral TMZ (n = 20) or placebo (n = 19), 20 mg tid, 14 days prior to departure until the end of study. The 2018 Lake Louise Score questionnaire, echocardiography, assessments of physical working capacity, circulating markers of myocardial energy metabolism and fatigue were performed both before departure and arrival at highland. At follow-up, TMZ significantly reduced the incidence of HAF (p = 0.038), reversed cardiorespiratory fitness impairment, decreased left ventricular end-systolic volume (LVESV, p = 0.032) and enhanced left ventricular ejection fraction (LVEF, p = 0.015) at highland. Relative to the placebo group, the TMZ group had significantly lower LDH (p = 0.025) and lactate levels before (p

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3bd0da6663ffac6a4fd37aca5ece482eTest
https://pubmed.ncbi.nlm.nih.gov/31125823Test

المؤلفون: Yuju Pu, Juan Yu, Fei Wang, Hongmei Chen, Jinqiao Qian, Zhuoran Wang, Wang Wei, Wei Yang

المصدر: Biomedicine & Pharmacotherapy, Vol 115, Iss, Pp-(2019)

مصطلحات موضوعية: 0301 basic medicine, Cell Survival, Apoptosis, Cardioprotection, RM1-950, Pharmacology, medicine.disease_cause, Cell Line, Receptor, Cannabinoid, CB2, 03 medical and health sciences, 0302 clinical medicine, Western blot, microRNA, medicine, Animals, Myocytes, Cardiac, medicine.diagnostic_test, L-Lactate Dehydrogenase, Chemistry, Cnr2, Adenylate Kinase, General Medicine, Transfection, Hydrogen Peroxide, Rats, Gene expression profiling, Oxygen, MicroRNAs, Oxidative Stress, 030104 developmental biology, Real-time polymerase chain reaction, Gene Expression Regulation, 030220 oncology & carcinogenesis, AK1, Therapeutics. Pharmacology, Oxidative stress, Dexmedetomidine

الوصف: Background Dexmedetomidine (Dex) can confer cardioprotective effects against ischemia/reperfusion (I/R) injury. While there are no studies addressing cardioprotection of Dex via regulation of microRNAs. The purpose of this study was to examine the roles and mechanisms of microRNA in cardioprotection of dexmedetomidine. Methods Rat heart Langendorff preparation was established. We assayed expression profiling of miRNAs in perfused rat hearts and predicted Target genes using MiRanda, MiRDB, and TargetScan. Oxide stress (H2O2) was employed to simulate I/R injury. miR-665 mimic, inhibitor, and siRNA of AK1 and Cnr2 were transfected to H9C2. The real-time quantitative polymerase chain reaction was used to quantify miR-665 and Ak1 and Cnr2 mRNA. The apoptosis of the cells was examined. The expression levels of cleaved caspase-3, Bcl-2, Bax, AK1, and Cnr2 were detected by Western blot. The combination between miR-665 and the 3′-untranslated region of AK1 and Cnr2 was validated by a luciferase reporter assay. Results Dex precondition down-regulated miR-665 expression in hearts compared to I/R group. Dex reduced miR-665 expression and apoptosis increased by oxide stress. However, up-regulation of miR-665 exacerbated the changes caused by oxide stress and inhibited the effects of Dex. Down-regulation of miR-665 also reduced apoptosis, but inhibition of AK1 and Cnr2 aggravated apoptosis. The luciferase reporter assay indicated that miR-665 could down-regulate expression levels of AK1 and Cnr2. Conclusions Dex precondition confers hearts protective effect against I/R injury by down-regulating expression of miR-665 and up-regulating expression of AK1 and Cnr2.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e4cc8e3a9a775374a09831bb720112c0Test
https://pubmed.ncbi.nlm.nih.gov/31026731Test