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Monocrotaline

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https://www.readbyqxmd.com/read/28926926/protective-effects-of-aloperin-on-monocroline-induced-pulmonary-hypertension-via-regulation-of-rho-a-rho-kinsase-pathway-in-rats
#1
Fan Wu, Wanxia Yao, Jiamei Yang, Min Zhang, Yanping Xu, Yinju Hao, Lin Yan, Yang Niu, Tao Sun, Jianqiang Yu, Ru Zhou
Pulmonary hypertension (PH) is fatal disease which closely involves Rho A/ Rho kinsase (ROCK) pathway. Aloperine is a main active alkaloid extracted from Sophora alopecuroides, which is a traditional Chinese herbal medicine that has been used widely. However, the effects of this alkaloid on pulmonary hypertension and its mechanisms remain unclear. Therefore, this study is designed to investigate whether aloperine has protective effects on PH induced by monocrotaline, whether these effects may be related to regulation of RhoA/ROCK pathway in rats...
September 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28924387/activation-of-nrf2-attenuates-pulmonary-vascular-remodeling-via-inhibiting-endothelial-to-mesenchymal-transition-an-insight-from-a-plant-polyphenol
#2
Yucai Chen, Tianyi Yuan, Huifang Zhang, Yu Yan, Danshu Wang, Lianhua Fang, Yang Lu, Guanhua Du
The endothelial-to-mesenchymal transition (EndMT) has been demonstrated to be involved in pulmonary vascular remodeling. It is partly attributed to oxidative and inflammatory stresses in endothelial cells. In current study, we conducted a series of experiments to clarify the effect of salvianolic acid A (SAA), a kind of polyphenol compound, in the process of EndMT in human pulmonary arterial endothelial cells and in vivo therapeutic efficacy on vascular remodeling in monocrotaline (MCT)-induced EndMT. EndMT was induced by TGFβ1 in human pulmonary arterial endothelial cells (HPAECs)...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28911605/7-n-acetylcysteine-pyrrole-conjugate-a-potent-dna-reactive-metabolite-of-pyrrolizidine-alkaloids
#3
Xiaobo He, Liang Ma, Qingsu Xia, Peter P Fu
Plants containing pyrrolizidine alkaloids (PAs) are widespread throughout the world and are the most common poisonous plants affecting livestock, wildlife, and humans. PAs require metabolic activation to form reactive dehydropyrrolizidine alkaloids (dehydro-PAs) that are capable of alkylating cellular DNA and proteins, form (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA and DHP-protein adducts, and lead to cytotoxicity, genotoxicity, and tumorigenicity. In this study, we determined that the metabolism of riddelliine and monocrotaline by human and rat liver microsomes in the presence of N-acetylcysteine both produced 7-N-acetylcysteine-DHP (7-NAC-DHP) and DHP...
October 2016: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28910144/ask1-inhibition-halts-disease-progression-in-preclinical-models-of-pulmonary-arterial-hypertension
#4
Grant R Budas, Mario Boehm, Baktybek Kojonazarov, Gayathri Viswanathan, Xia Tian, Swathi Veeroju, Tatyana Novoyatleva, Friedrich Grimminger, Ford Hinojosa-Kirschenbaum, Hossein A Ghofrani, Norbert Weissmann, Werner Seeger, John T Liles, Ralph T Schermuly
RATIONALE Progression of pulmonary arterial hypertension (PAH) is associated with pathologic remodeling of the pulmonary vasculature and the right ventricle (RV). Oxidative stress drives the remodeling process through activation of mitogenactivated protein kinases (MAPKs) which stimulate apoptosis, inflammation and fibrosis. OBJECTIVES We investigated whether pharmacological inhibition of the redoxsensitive apical MAPK Apoptosis Signal-Regulating Kinase 1 (ASK1) can halt the progression of pulmonary vascular and RV remodeling...
September 14, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28887874/small-molecule-inhibition-of-murf1-attenuates-skeletal-muscle-atrophy-and-dysfunction-in-cardiac-cachexia
#5
Thomas Scott Bowen, Volker Adams, Sarah Werner, Tina Fischer, Paulien Vinke, Maria Noel Brogger, Norman Mangner, Axel Linke, Peter Sehr, Joe Lewis, Dittmar Labeit, Alexander Gasch, Siegfried Labeit
BACKGROUND: Muscle ring finger 1 (MuRF1) is a muscle-specific ubiquitin E3 ligase activated during clinical conditions associated with skeletal muscle wasting. Yet, there remains a paucity of therapeutic interventions that directly inhibit MuRF1 function, particularly in vivo. The current study, therefore, developed a novel compound targeting the central coiled coil domain of MuRF1 to inhibit muscle wasting in cardiac cachexia. METHODS: We identified small molecules that interfere with the MuRF1-titin interaction from a 130 000 compound screen based on Alpha Technology...
September 8, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/28867639/animal-models-of-pulmonary-arterial-hypertension-a-systematic-review-and-meta-analysis-of-data-from-6-126-animals
#6
Katarzyna Sztuka, Magdalena Jasińska-Stroschein
Numerous animal models of pulmonary hypertension are currently available. A systematic review and meta-analysis was performed of a number of experimental studies of disease induction based on several animal models. A meta-analysis was performed of 291 publications discussing the efficacy of 611 interventions to introduce disease pulmonary hypertension in 6,126 animals. A meta-regression analysis was done to assess the effect of prolonged periods of disease induction on the outcomes. A random-effects meta-analysis was used to assess the impact of study characteristics and seek evidence of publication bias...
August 31, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28855544/prostaglandin-e1-attenuates-pulmonary-artery-remodeling-by-activating-phosphorylation-of-creb-and-the-pten-signaling-pathway
#7
Ying-Ju Lai, Hsao-Hsun Hsu, Gwo-Jyh Chang, Shu-Hui Lin, Wei-Jan Chen, Chung-Chi Huang, Jong-Hwei S Pang
The depletion of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and phosphatase and tensin homolog (PTEN) is the critical mediator of pulmonary arterial hypertension (PAH). We hypothesized that the activation of phosphorylated CREB (pCREB) and PTEN could inhibit the AKT signaling pathway to attenuate pulmonary arterial remodeling in rats with monocrotaline-induced PAH. We observed decreased PTEN and pCREB in idiopathic PAH versus control tissue. We reduced PTEN using small interfering RNA in human control pulmonary arterial smooth muscle cells (PASMCs) and observed an increase in pAKT...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28854338/effects-of-ovariectomy-in-antioxidant-defence-systems-in-right-ventricle-of-female-rats-with-pulmonary-arterial-hypertension-induced-by-monocrotaline
#8
Rafaela Siqueira, Rafael Colombo, Adriana Conzatti, Alexandre Luz De Castro, Cristina Campos Carraro, Angela Maria Vicente Tavares, Tania Gatelli Fernandes, Alex Sander Araujo, Adriane Belló-Klein
The aim of this study was to evaluate the impact of ovariectomy on oxidative stress in the right ventricle (RV) of female rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). Rats were divided into four groups (n=6/group): sham (S), sham + MCT (SM), ovariectomized (O), and ovariectomized + MCT (OM). MCT (60 mg/kg i.p) was injected 1 week after ovariectomy or sham surgery. Three weeks after,, echocardiographic analysis and RV catheterisation were performed. RV morphometric, biochemical, and protein expression analysis through western blotting were done...
August 30, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28851623/diethylcarbamazine-a-potential-treatment-drug-for-pulmonary-hypertension
#9
Edlene Lima Ribeiro, Ingrid Tavares Fragoso, Fabiana Oliveira Dos Santos Gomes, Amanda Costa Oliveira, Amanda Karoline Soares E Silva, Patrícia Martins E Silva, Bianca Torres Ciambarella, Isalira Peroba Rezende Ramos, Christina Alves Peixoto
The present study demonstrated the potential effects of diethylcarbamazine (DEC) on monocrotaline (MCT)-induced pulmonary hypertension. MCT solution (600mg/kg) was administered once per week, and 50mg/kg body weight of DEC for 28days. Three C57Bl/6 male mice groups (n=10) were studied: Control; MCT28, and MCT28/DEC. Echocardiography analysis was performed and lung tissues were collected for light microscopy (hematoxylin-eosin and Masson's trichrome staining), immunohistochemistry (αSMA, FADD, caspase 8, caspase 3, BAX, BCL2, cytochrome C and caspase 9) western blot (FADD, caspase 8, caspase 3, BAX, BCL2, cytochrome C and caspase 9) and qRt-PCR (COL-1α and αSMA)...
October 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28844483/serum-microrna-122-3p-microrna-194-5p-and-microrna-5099-are-potential-toxicological-biomarkers-for-the-hepatotoxicity-induced-by-airpotato-yam
#10
Rui Yang, Fan Yang, Zhenlin Huang, Yao Jin, Yuchen Sheng, Lili Ji
Airpotato yam (the rhizome of Dioscorea bulbifera L.) is traditionally used to treat thyroid disease and various cancers in China. However, it was found to cause hepatotoxicity during clinical practice. This study aims to identify candidate serum microRNAs (miRNAs) as diagnostic biomarkers for the liver injury induced by Airpotato yam. The results of serum alanine/aspartate aminotransferase (ALT/AST) showed the remarkable hepatotoxicity induced by ethyl acetate fraction of Airpotato yam (EF) (450mg/kg) and diosbulbin B (DB) (300mg/kg) in mice...
August 24, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28837618/therapeutic-benefits-of-intravenous-cardiosphere-derived-cell-therapy-in-rats-with-pulmonary-hypertension
#11
Ryan C Middleton, Mario Fournier, Xuan Xu, Eduardo Marbán, Michael I Lewis
Pulmonary arterial hypertension (PAH) is a progressive condition characterized by occlusive pulmonary arteriopathy, in which survival remains poor despite pharmacologic advances. The aim of this study was to evaluate the ability of cardiosphere-derived cells (CDCs), cardiac progenitor cells with potent anti-inflammatory and immunomodulatory properties, to attenuate hemodynamic and morphometric remodeling of the right ventricle (RV) and pulmonary arterioles in rats with established monocrotaline (MCT)-induced PAH...
2017: PloS One
https://www.readbyqxmd.com/read/28818515/integrative-analysis-of-hepatic-microrna-and-mrna-to-identify-potential-biological-pathways-associated-with-monocrotaline-induced-liver-injury-in-mice
#12
Zhenlin Huang, Minwei Chen, Jiaqi Zhang, Yuchen Sheng, Lili Ji
Pyrrolizidine alkaloids (PAs) are a type of natural hepatotoxic compounds. Monocrotaline (MCT), belongs to PAs, is a main compound distributed in medicinal herb Crotalaria ferruginea Grah. ex Benth. This study aims to identify the potential biological signaling pathway associated with MCT-induced liver injury by analyzing the integrative altered hepatic microRNA (miRNA) and mRNA expression profile. C57BL/6 mice were orally given with MCT (270, 330mg/kg). Serum alanine/aspartate aminotransferase (ALT/AST) activity, total bilirubin (TBil) amount and liver histological evaluation showed the liver injury induced by MCT...
October 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28798258/preserved-right-ventricular-integrity-in-a-new-telemetric-rat-model-of-severe-pulmonary-hypertension
#13
Catharina Schreiber, Magdalena S Eilenberg, Attila Kiss, Helga Bergmeister, Bruno K Podesser, Julia Mascherbauer, Diana Bonderman
Telemetric monitoring of hemodynamic parameters has become an established standard in experimental models of pulmonary arterial hypertension (PAH). To that purpose, a dedicated catheter is usually implanted through the right ventricular wall of study animals. Drawbacks of this standard technique are: obtained pressures are from the right ventricle and therefore only surrogates for pulmonary arterial pressures, and furthermore, right ventricular myocardium is always damaged to a certain degree. To overcome shortcomings of standard hemodynamic assessment, we modified an established rat model, where severe PAH is induced by left-sided pneumonectomy plus monocrotaline injection...
August 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28793822/dose-response-head-to-head-comparison-of-inodilators-dobutamine-milrinone-and-levosimendan-in-chronic-experimental-pulmonary-hypertension
#14
Marta Tavares-Silva, Mohamed Alaa, Sara Leite, José Oliveira-Pinto, Lucas Lopes, Adelino F Leite-Moreira, André P Lourenço
The choice of inodilator drug in the acute management of patients with pulmonary hypertension (PH) having right ventricular (RV) failure remains unsettled and challenging. Comprehensive experimental evaluations may provide further insight and fundamental translational research clues to support inodilator selection and clinical trial design. Our aim was to compare acute dose-response hemodynamic effects of inodilators dobutamine (DOB), milrinone (MIL), and levosimendan (LEV) in chronic experimental PH. Seven-week-old male Wistar rats were randomly injected with 60 mg·kg(-1) monocrotaline (MCT) or vehicle (Ctrl, n = 7) and underwent systemic and pulmonary artery (PA) pressure and RV pressure-volume (PV) hemodynamic evaluation under halogenate anesthesia 24 to 30 days after injection...
September 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28776262/visceral-adipose-tissue-derived-serine-protease-inhibitor-prevents-the-development-of-monocrotaline-induced-pulmonary-arterial-hypertension-in-rats
#15
Yuzaburo Sakamoto, Satoshi Kameshima, Chiharu Kakuda, Yuta Okamura, Tomoko Kodama, Muneyoshi Okada, Hideyuki Yamawaki
Visceral adipose tissue-derived serine protease inhibitor (vaspin), a recently identified adipocytokine, inhibits inflammation, migration, and apoptosis of vascular cells. We have recently demonstrated that chronic administration of vaspin to spontaneously hypertensive rats partly prevents systemic hypertension through inhibiting inflammation and remodeling of vascular wall. Pulmonary arterial (PA) hypertension (PAH) is caused by PA remodeling, contractile dysfunction, and inflammatory responses. We tested the hypothesis that vaspin could prevent development of PAH in animal model...
August 3, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28757567/arginase-inhibition-reverses-monocrotaline-induced-pulmonary-hypertension
#16
Christian Jung, Katja Grün, Stefan Betge, John Pernow, Malte Kelm, Johanna Muessig, Maryna Masyuk, Friedhelm Kuethe, Bernadin Ndongson-Dongmo, Reinhard Bauer, Alexander Lauten, P Christian Schulze, Alexander Berndt, Marcus Franz
Pulmonary hypertension (PH) is a heterogeneous disorder associated with a poor prognosis. Thus, the development of novel treatment strategies is of great interest. The enzyme arginase (Arg) is emerging as important player in PH development. The aim of the current study was to determine the expression of ArgI and ArgII as well as the effects of Arg inhibition in a rat model of PH. PH was induced in 35 Sprague-Dawley rats by monocrotaline (MCT, 60 mg/kg as single-dose). There were three experimental groups: sham-treated controls (control group, n = 11), MCT-induced PH (MCT group, n = 11) and MCT-induced PH treated with the Arg inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA; MCT/NorNoha group, n = 13)...
July 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28755990/nf-%C3%AE%C2%BAb-mediated-mir-130a-modulation-in-lung-microvascular-cell-remodeling-implication-in-pulmonary-hypertension
#17
Li Li, Il-Kwon Kim, Valorie Chiasson, Piyali Chatterjee, Sudhiranjan Gupta
Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease which is associated with pulmonary arterial endothelial cells (PAEC) dysfunction and pulmonary arterial smooth muscle cells proliferation. Moreover, inflammation is contributing a critical role in EC dysfunction and remains elusive. Nuclear factor-kappa B (NF-κB) is a master transcriptional regulator in various cardiovascular pathologies; but, NF-κB's role in EC dysfunction in unknown. Our previous study using cardiac and lung specific IκBα mutant mice (3M and IKBM) showed that PAH induced right ventricular hypertrophy (RVH) was prevented in monocrotaline (MCT) treated 3M and IKBM mice, compared to the wild-type mice...
July 26, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28733311/regional-septal-hinge-point-injury-contributes-to-adverse-biventricular-interactions-in-pulmonary-hypertension
#18
Eva Amalie Nielsen, Kenichi Okumura, Mei Sun, Vibeke E Hjortdal, Andrew N Redington, Mark K Friedberg
Death and morbidity in pulmonary arterial hypertension (PAH) are often due to right ventricular (RV) failure and associated left ventricular (LV) dysfunction. We investigated regional myocardial remodeling and function as the basis for adverse ventricular-ventricular interactions in experimental chronic RV pressure overload. Two distinct animal models were studied: A rabbit model of increased RV pressure-load through progressive pulmonary artery banding A rat model of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH)...
July 2017: Physiological Reports
https://www.readbyqxmd.com/read/28711939/baicalin-attenuates-monocrotaline-induced-pulmonary-hypertension-through-bone-morphogenetic-protein-signaling-pathway
#19
Zhaohua Zhang, Luan Zhang, Chao Sun, Feng Kong, Jue Wang, Qian Xin, Wen Jiang, Kaili Li, Ou Chen, Yun Luan
Baicalin, a flavonoid compound extracted from roots of Scutellaria baicalensis Georgi (huang qin), it has been shown to effectively attenuates pulmonary hypertension (PH), however, the potential mechanism remains unexplored. In this study, we investigated the potential mechanism of baicalin on monocrotaline (MCT)-induced PH in rats. The results showed that baicalin attenuated lung damage in PH rat model through inhibiting the pulmonary arterial smooth muscle cell proliferation and induction of cells apoptosis...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28704260/%C3%AE-solanine-reverses-pulmonary-vascular-remodeling-and-vascular-angiogenesis-in-experimental-pulmonary-artery-hypertension
#20
Xiaowei Nie, Youai Dai, Jianxin Tan, Yuan Chen, Guowei Qin, Wenjun Mao, Jian Zou, Yanhua Chang, Qian Wang, Jingyu Chen
OBJECTIVE: Similar to cancer, pulmonary arterial hypertension (PAH) is characterized by vascular remodeling, which leads to obliteration of the small pulmonary arteriole, with marked proliferation of pulmonary artery smooth muscle cells (PASMC) and/or endothelial cells dysfunction. Aberrant expression of tumor suppressor genes is closely associated with susceptibility to PAH. We hypothesized that α-solanine, a glycoalkaloid found in members of the nightshade family known to have antitumor activity in different cancers, reverses experimental PAH by activating the tumor suppressor-axis inhibition protein 2 (AXIN2)...
July 12, 2017: Journal of Hypertension
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