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Monocrotaline

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https://www.readbyqxmd.com/read/28431936/galectin-3-mediates-the-pulmonary-arterial-hypertension-induced-right-ventricular-remodeling-through-interacting-with-nadph-oxidase-4
#1
Jingni He, Xiaohui Li, Hui Luo, Tangzhiming Li, Lin Zhao, Qiangqiang Qi, Yuwei Liu, Zaixin Yu
Pulmonary arterial hypertension (PAH) is a progressive disorder that affects both pulmonary vasculature and the heart. The response of the right ventricle (RV) to the increased afterload is an important determinant of the PAH final outcome. Galectin-3 (Gal-3), a novel biomarker in left cardiac remodeling, takes part in multiple pathophysiological processes including the inflammation, fibrosis, immunity, and oxidative stress. The levels of Gal-3 are elevated in PAH patients, although the exact mechanisms underlie the PAH-induced right ventricular structural changes remain unclear...
March 27, 2017: Journal of the American Society of Hypertension: JASH
https://www.readbyqxmd.com/read/28417056/therapeutic-effect-of-prostaglandin-e1-in-monocrotaline-induced-pulmonary-arterial-hypertension-rats
#2
Jae Chul Lee
Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in pulmonary arterial pressure and excessive thickening and remodeling of distal small pulmonary arteries. During disease progression, PAH include increase in mean pulmonary arterial pressure, right ventricular (RV) enlargement, increased pulmonary vascular resistance, and smooth muscle hypertrophy in pulmonary arterioles. Several anti-PAH therapies targeting various pathways involved in PAH progression have been approved by the Food and Drug Adminstration...
March 2017: Anatomy & Cell Biology
https://www.readbyqxmd.com/read/28410199/chronic-intratracheal-application-of-the-soluble-guanylyl-cyclase-stimulator-bay-41-8543-ameliorates-experimental-pulmonary-hypertension
#3
Matthieu Amirjanians, Bakytbek Egemnazarov, Akylbek Sydykov, Baktybek Kojonazarov, Ralf Brandes, Himal Luitel, Kabita Pradhan, Johannes-Peter Stasch, Gorden Redlich, Norbert Weissmann, Friedrich Grimminger, Werner Seeger, Hossein Ghofrani, Ralph Schermuly
Dysfunction of the NO/sGC/cGMP signaling pathway has been implicated in the pathogenesis of pulmonary hypertension (PH). Therefore, agents stimulating cGMP synthesis via sGC are important therapeutic options for treatment of PH patients. An unwanted effect of this novel class of drugs is their systemic hypotensive effect. We tested the hypothesis that aerosolized intra-tracheal delivery of the sGC stimulator BAY41-8543 could diminish its systemic vasodilating effect.Pharmacodynamics and -kinetics of BAY41-8543 after single intra-tracheal delivery was tested in healthy rats...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400261/involvement-of-astrocytic-cyp1a1-isoform-in-the-metabolism-and-toxicity-of-the-alkaloid-pyrrolizidine-monocrotaline
#4
Ravena P Nascimento, Joana L Oliveira, José Leilton C Carvalho, William A Santos, Thyago Rubens C Pires, Maria José M Batatinha, Ramon S El-Bachá, Victor Diógenes A Silva, Silvia L Costa
Monocrotaline (MCT) and its pyrrole derivative, dehydromonocrotaline (DHMC), interact with molecular targets in cells of the central nervous system. DHMC presents higher toxicity than MCT indicating that its metabolism of MCT is a critical step of this alkaloid toxicity. This study sought to elucidate the metabolism and the toxicity of MCT in C6 astrocyte cell line and primary cultures of rat astrocytes by investigating metabolic enzymatic mechanisms of the cytochrome P450 (CYP) system and conjugation with glutathione...
April 8, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28391867/ultrasensitive-immunoassay-for-monocrotaline-using-monoclonal-antibody-produced-by-n-n-carbonyldiimidazole-mediated-hapten-carrier-protein-conjugates
#5
Seiichi Sakamoto, Rika Nagamitsu, Gorawit Yusakul, Tomofumi Miyamoto, Hiroyuki Tanaka, Satoshi Morimoto
Monocrotaline (MCT) is a naturally occurring pyrrolizidine alkaloid mainly produced in plant genus Crotalaria (Fabaceae), in which various toxicities have been reported. Recently, demand of quantitative analysis for determination/detection of MCT has increased because MCT in plants can be transferred to human by food chain, leading to intoxication. In this study, monoclonal antibody (MAb) against MCT (MAb 4B8) was produced by unique one-pot conjugation between hydrolysate of MCT, retronecine (RN) and consecutive lysine residues of bovine-serum albumin (BSA) through N,N'-carbonyldiimidazole (CDI) mediated method...
June 1, 2017: Talanta
https://www.readbyqxmd.com/read/28373627/effects-of-transplanted-human-cord-blood-mononuclear-cells-on-pulmonary-hypertension-in-immunodeficient-mice-and-their-distribution
#6
Mikio Sugano, Homare Yoshida, Hirotsugu Kurobe, Hiroki Arase, Hajime Kinoshita, Takashi Kitaichi, Noriko Sugasawa, Soichiro Nakayama, Kazuhisa Maeda, Minoru Irahara, Tetsuya Kitagawa
OBJECTIVES: To investigate the effects of human umbilical cord blood-derived mononuclear cell (hUCB-MNC) transplantation on pulmonary hypertension (PH) induced by monocrotaline (MCT) in immunodeficient mice and their distribution. METHODS: MCT was administered to BALB/c Slc-nu/nu mice, and PH was induced in mice 4 weeks later. Fresh hUCB-MNCs harvested from a human donor after her delivery were injected intravenously into those PH mice. The medial thickness of pulmonary arterioles, ratio of right ventricular to septum plus left ventricular weight (RV/S+LV), and ratio of acceleration time to ejection time of pulmonary blood flow waveform (AT/ET) were determined 4 weeks after hUCB-MNC transplantation...
2017: Journal of Medical Investigation: JMI
https://www.readbyqxmd.com/read/28363184/treatment-with-platelet-derived-growth-factor-pdgf-and-rock-inhibitors-is-related-to-declined-nerve-growth-factor-ngf-signaling-in-an-experimental-model-of-rat-pulmonary-hypertension
#7
Magdalena Jasińska-Stroschein, Katarzyna Oszajca, Weronika Świtlik, Justyna Ruchwa, Daria Orszulak-Michalak
BACKGROUND: Recent studies reveal that nerve growth factor (NGF) plays a critical role in the pathobiology of pulmonary hypertension (PH). The aim of the present study is to clarify the relationship between NGF signaling and treatment with PDGF or ROCK inhibitors in an animal model of PH. METHODS: Lung tissues were obtained from animals with monocrotaline (MCT)-challenged PH which had been administered long term imatinib, fasudil or statin. Reversal of disease was indicated by decreases in right ventricle pressure (RVP) and hypertrophy...
February 1, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28359821/rapamycin-nanoparticles-localize-in-diseased-lung-vasculature-and-prevent-pulmonary-arterial-hypertension
#8
Victor Segura-Ibarra, Javier Amione-Guerra, Ana S Cruz-Solbes, Francisca E Cara, David A Iruegas-Nunez, Suhong Wu, Keith A Youker, Arvind Bhimaraj, Guillermo Torre-Amione, Mauro Ferrari, Harry Karmouty-Quintana, Ashrith Guha, Elvin Blanco
Vascular remodeling resulting from pulmonary arterial hypertension (PAH) leads to endothelial fenestrations. This feature can be exploited by nanoparticles (NP), allowing them to extravasate from circulation and accumulate in remodeled pulmonary vessels. Hyperactivation of the mTOR pathway in PAH drives pulmonary arterial smooth muscle cell proliferation. We hypothesized that rapamycin (RAP)-loaded NPs, an mTOR inhibitor, would accumulate in diseased lungs, selectively targeting vascular mTOR and preventing PAH progression...
March 28, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28358421/extravasated-platelet-aggregation-in-the-livers-of-rats-with-drug%C3%A2-induced-hepatic-sinusoidal-obstruction-syndrome
#9
Miki Hirata, Hidehiro Tajima, Tomoharu Miyashita, Takashi Miyata, Shinichi Nakanuma, Isamu Makino, Hironori Hayashi, Katsunobu Oyama, Hiroyuki Takamura, Itasu Ninomiya, Sachio Fushida, Hiroki Nakata, Shoichi Iseki, Shinichi Harada, Tomohiko Wakayama, Tetsuo Ohta
Oxaliplatin-based chemotherapy plays an important role in the treatment of colorectal liver metastases. Oxaliplatin, however, causes sinusoidal obstruction syndrome (SOS), which is characterized by portal hypertension, splenomegaly, thrombocytopenia, and liver dysfunction. SOS is diagnosed histopathologically by disruption of the sinusoidal endothelium, collagen deposition, fibrosis especially around zone 3, dilatation of the sinusoidal space and congestion. This study assessed the characteristics of a rat model of SOS...
March 28, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28351900/long-noncoding-rna-mantis-facilitates-endothelial-angiogenic-function
#10
Matthias S Leisegang, Christian Fork, Ivana Josipovic, Florian Richter, Jens Preussner, Jiong Hu, Matthew J Miller, Jeremy N Epah, Patrick Hofmann, Stefan Günther, Franziska Moll, Chanil Valasarajan, Juliana Heidler, Yuliya Ponomareva, Thomas M Freiman, Lars Maegdefessel, Karl H Plate, Michel Mittelbronn, Shizuka Uchida, Carsten Künne, Konstantinos Stellos, Ralph T Schermuly, Norbert Weissmann, Kavi Devraj, Ilka Wittig, Reinier A Boon, Stefanie Dimmeler, Soni S Pullamsetti, Mario Looso, Francis J Miller, Ralf P Brandes
Background -The angiogenic function of endothelial cells is regulated by numerous mechanisms but the impact of long noncoding RNAs (lncRNAs) has hardly been studied. We set out to identify novel and functionally important endothelial lncRNAs. Methods -Epigenetically controlled lncRNAs in human umbilical vein endothelial cells (HUVEC) were searched by exon-array analysis after knockdown of the histone demethylase JARID1B. Molecular mechanisms were investigated by RNA Pulldown and Immunoprecipitation, Mass spectrometry, Micro-array, several knockdown approaches, CRIPSR-Cas9, Assay for Transposase-Accessible Chromatin-Sequencing and chromatin immunoprecipitation in HUVEC...
March 28, 2017: Circulation
https://www.readbyqxmd.com/read/28344760/severe-pulmonary-hypertension-in-aging-female-apolipoprotein-e-deficient-mice-is-rescued-by-estrogen-replacement-therapy
#11
Soban Umar, Rod Partow-Navid, Gregoire Ruffenach, Andrea Iorga, Shayan Moazeni, Mansoureh Eghbali
BACKGROUND: Apolipoprotein E (ApoE) is a multifunctional protein, and its deficiency leads to the development of atherosclerosis in mice. Patients with pulmonary hypertension (PH) have reduced expression of ApoE in lung tissue. ApoE is known to inhibit endothelial and smooth muscle cell proliferation and has anti-inflammatory and anti-platelet aggregation properties. Young ApoE-deficient mice have been shown to develop PH on high fat diet. The combined role of female sex and aging in the development of PH has not been investigated before...
2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28340591/altered-mtor-and-beclin-1-mediated-autophagic-activation-during-right-ventricular-remodeling-in-monocrotaline-induced-pulmonary-hypertension
#12
Yan Deng, Weifeng Wu, Shenglan Guo, Yuming Chen, Chang Liu, Xingcui Gao, Bin Wei
BACKGROUND: Right ventricular structure and function is a major predictor of outcomes in pulmonary hypertension (PH), yet the underlying mechanisms remain poorly understood. Growing evidence suggests the importance of autophagy in cardiac remodeling; however, its dynamics in the process of right ventricle(RV) remodeling in PH has not been fully explored. We sought to study the time course of cardiomyocyte autophagy in the RV in PH and determine whether mammalian target of rapamycin (mTOR) and Beclin-1 hypoxia-related pro-autophagic pathways are underlying mechanisms...
March 24, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28337251/pentaerythritol-tetranitrate-in-vivo-treatment-improves-oxidative-stress-and-vascular-dysfunction-by-suppression-of-endothelin-1-signaling-in-monocrotaline-induced-pulmonary-hypertension
#13
Sebastian Steven, Matthias Oelze, Moritz Brandt, Elisabeth Ullmann, Swenja Kröller-Schön, Tjebo Heeren, Lan P Tran, Steffen Daub, Mobin Dib, Dirk Stalleicken, Philip Wenzel, Thomas Münzel, Andreas Daiber
Objective. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH). The role of the nitrovasodilator pentaerythritol tetranitrate (PETN) on endothelial function and oxidative stress in PAH has not yet been defined. Methods and Results. PAH was induced by monocrotaline (MCT, i.v.) in Wistar rats. Low (30 mg/kg; MCT30), middle (40 mg/kg; MCT40), or high (60 mg/kg; MCT60) dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28332747/ultra-performance-liquid-chromatography-hyphenated-with-quadrupole-orbitrap-mass-spectrometry-for-simultaneous-determination-of-necine-core-structure-pyrrolizidine-alkaloids-in-crotalaria-sessiliflora-l-without-all-corresponding-standards
#14
Wei Zhang, Wenbei Huai, Yi Zhang, Jincan Shen, Xunyou Tang, Xiujuan Xie, Ke Wang, Huajun Fan
INTRODUCTION: Crotalaria sessiliflora L. is a Chinese traditional herb for treatment of cutaneum carcinoma and cervical carcinoma. In addition to monocrotaline, coexisting pyrrolizidine alkaloids (PAs) also require further quantification for quality control and pharmaceutical uses of the herb. OBJECTIVE: To establish a UPLC-Q-Orbitrap/MS method of simultaneous determination of coexisting PAs with same parent structure for quality control and comprehensive researches of Crotalaria sessiliflora L...
March 23, 2017: Phytochemical Analysis: PCA
https://www.readbyqxmd.com/read/28332363/optimal-dose-and-timing-of-umbilical-stem-cells-treatment-in-pulmonary-arterial-hypertensive-rats
#15
Hyeryon Lee, Kwan Chang Kim, Soo Jin Choi, Young Mi Hong
PURPOSE: Pulmonary arterial hypertension (PAH) is a fatal disease which is characterized by an increase in pulmonary arterial pressure leading to increases in right ventricular afterload. Human umbilical cord blood derived-mesenchymal stem cells (hUCB-MSCs) administered via the jugular vein have been previously shown to improve PAH by reversal treatment. However, the effect of low dosage and transfusion timing of hUCB-MSCs on PAH has not yet been clearly established. Obviously, low dosage treatment can lead to a reduction in costs...
May 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28330842/monocrotaline-induces-endothelial-injury-and-pulmonary-hypertension-by-targeting-the-extracellular-calcium-sensing-receptor
#16
Rui Xiao, Yuan Su, Tian Feng, Mengxiang Sun, Bingxun Liu, Jiwei Zhang, Yankai Lu, Jiansha Li, Tao Wang, Liping Zhu, Qinghua Hu
BACKGROUND: Monocrotaline has been widely used to establish an animal model of pulmonary hypertension. The molecular target underlying monocrotaline-induced pulmonary artery endothelial injury and pulmonary hypertension remains unknown. The extracellular calcium-sensing receptor (CaSR) and particularly its extracellular domain hold the potential structural basis for monocrotaline to bind. This study aimed to reveal whether monocrotaline induces pulmonary hypertension by targeting the CaSR...
March 22, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28321539/secoisolariciresinol-diglucoside-attenuates-cardiac-hypertrophy-and-oxidative-stress-in-monocrotaline-induced-right-heart-dysfunction
#17
Stephanie Puukila, Rafael Oliveira Fernandes, Patrick Türck, Cristina Campos Carraro, Jéssica Hellen Poletto Bonetto, Bruna Gazzi de Lima-Seolin, Alex Sander da Rosa Araujo, Adriane Belló-Klein, Douglas Boreham, Neelam Khaper
Pulmonary arterial hypertension (PAH) occurs when remodeling of pulmonary vessels leads to increased pulmonary vascular resistance resulting in increased pulmonary arterial pressure. Increased pulmonary arterial pressure results in right ventricle hypertrophy and eventually heart failure. Oxidative stress has been implicated in the pathogenesis of PAH and may play a role in the regulation of cellular signaling involved in cardiac response to pressure overload. Secoisolariciresinol diglucoside (SDG), a component from flaxseed, has been shown to reduce cardiac oxidative stress in various pathophysiological conditions...
March 20, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28301419/effects-of-sevoflurane-on-hemodynamics-and-inducible-nitric-oxide-synthase-soluble-guanylate-cyclase-signaling-pathway-in-a-rat-model-of-pulmonary-arterial-hypertension
#18
Gang Qin, Hui Luo, Xiaoqing Yin, Lu Wang, Junjie Zhang, Yanan Cao, Zhong Zhang, Zhi Ye, E Wang
BACKGROUND: The effects of sevoflurane on right ventricular (RV) function are incompletely understood. In a rat model of experimentally induced pulmonary arterial hypertension (PAH), we studied effects of sevoflurane on RV function and the expression of inducible nitric oxide synthase/soluble guanylate cyclase (iNOS/sGC) signaling pathway. We hypothesized that sevoflurane would improve RV function in rats with PAH via a iNOS/sGC pathway. METHODS: To induce PAH, Sprague-Dawley rats were randomly assigned to treatment with monocrotaline or normal saline...
March 15, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28292027/claudin-1-regulates-pulmonary-artery-smooth-muscle-cell-proliferation-through-the-activation-of-erk1-2
#19
Xiandong Cheng, Yi Wang, Huilong Chen, Yongjian Xu, Weining Xiong, Tao Wang
Tumor necrosis factor alpha (TNF-α), a crucial inflammatory cytokine, is involved in the pathogenesis of pulmonary arterial hypertension (PAH). TNF-α can induce claudin-1 (CLDN1) expression and CLDN1 has been reported to be associated with the regulation of cellular functions including cell proliferation, migration. Thus, we aimed to explore whether CLDN1 participated in the etiology of PAH. Our study showed that CLDN1 expression was markedly increased in the lungs of rats with monocrotaline(MCT)-induced PAH, especially in the pulmonary arterial smooth muscle sections...
March 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28287603/shunt-surgery-right-heart-catheterization-and-vascular-morphometry-in-a-rat-model-for-flow-induced-pulmonary-arterial-hypertension
#20
Diederik E van der Feen, Michel Weij, Annemieke Smit-van Oosten, Lysanne M Jorna, Quint A J Hagdorn, Beatrijs Bartelds, Rolf M F Berger
In this protocol, PAH is induced by combining a 60 mg/kg monocrotalin (MCT) injection with increased pulmonary blood flow through an aorto-caval shunt (MCT+Flow). The shunt is created by inserting an 18-G needle from the abdominal aorta into the adjacent caval vein. Increased pulmonary flow has been demonstrated as an essential trigger for a severe form of PAH with distinct phases of disease progression, characterized by early medial hypertrophy followed by neointimal lesions and the progressive occlusion of the small pulmonary vessels...
February 11, 2017: Journal of Visualized Experiments: JoVE
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