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https://www.readbyqxmd.com/read/28546047/an-impedance-based-approach-using-human-ipsc-derived-cardiomyocytes-significantly-improves-in-vitro-prediction-of-in-vivo-cardiotox-liabilities
#1
Bryan Koci, Gregory Luerman, Anika Duenbostell, Ralf Kettenhofen, Heribert Bohlen, Luke Coyle, Brian Knight, Warren Ku, Walter Volberg, Joseph R Woska, Martha P Brown
Current in vitro approaches to cardiac safety testing typically focus on mechanistic ion channel testing to predict in vivo proarrhythmic potential. Outside of the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative, structural and functional cardiotoxicity related to chronic dosing effects are of great concern as these effects can impact compound attrition. Development and implementation of an in vitro cardiotoxicity screening platform that effectively identifies these liabilities early in the discovery process should reduce costly attrition and decrease preclinical development time...
May 22, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28544933/cardiotoxic-effect-of-levofloxacin-and-ciprofloxacin-in-rats-with-without-acute-myocardial-infarction-impact-on-cardiac-rhythm-and-cardiac-expression-of-kv4-3-kv1-2-and-nav1-5-channels
#2
Ahmed M Abdelrady, Sawsan A Zaitone, Noha E Farag, Manal S Fawzy, Yasser M Moustafa
Prolongation of QT interval is possible with fluoroquinolones, yet the underlying contributing factors have not been elucidated. Two widely used fluoroquinolone drugs were at the focus of this study in rats with/without acute myocardial dysfunction (AMI) induced by isoproterenol. The effects of levofloxacin and ciprofloxacin on the cardiac mRNA expression of rat Kv4.3, Kv1.2 and Nav1.5 mRNAs were determined. Administration of the two antibiotics produced dose-dependent changes in ECG parameters that were more prominent in rats with AMI than healthy rats; this was accompanied by elevations in serum lactate dehydrogenase and creatine kinase-MB...
May 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28544783/electrocardiography-s-role-in-screening-for-cardiotoxicity-in-adult-survivors-of-childhood-cancer-survivors-treated-with-anthracyclines-time-for-a-true-prospective-study
#3
https://www.readbyqxmd.com/read/28544073/hydrophilic-interaction-and-reversed-phase-ultra-performance-liquid-chromatography-tof-ms-for-metabolomic-analysis-of-veratrum-nigrum-induced-cardiotoxicity
#4
Ziheng Wei, Xu Dong, Hanzhe Zhang, Songyan Gao, Wei Shi, Feng Yang, Xin Dong
The acute cardiotoxicity induced by Veratrum nigrum (VN) is explored by analysing heart tissue metabolic profiles in mouse models and applying reversed-phase liquid chromatography mass spectrometry (RPLC-MS) and hydrophilic interaction liquid chromatography mass spectrometry (HILIC-MS) that are based on ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). An animal model of acute heart injury was established in mice via intra-gastric administration of VN. Then, electrocardiogram, echocardiograph monitoring of cardiac function and pathological examination were performed on mice both in the control and VN groups, and it was successfully verified that acute heart injury was caused...
May 22, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28543396/functional-and-structural-assessment-of-the-effect-of-human-umbilical-cord-blood-mesenchymal-stem-cells-in-doxorubicin-induced-cardiotoxicity
#5
Somia H Abd Allah, Samia Hussein, Mai M Hasan, Raghda H A Deraz, Wafaa F Hussein, Laila M E Sabik
Cardiomyopathy induced by doxorubicin (DOX) was recognized at an early stage and also several years after drug administration. Mesenchymal stem cells (MSCs) have many properties that make them suitable for preventive and/ or regenerative therapies. In this study, we evaluated the effect of MSCs in the functional and the structural improvement of DOX-induced cardiomyopathy in rats. Ninety adult male albino rats were randomly divided into three equal groups of thirty rats each: Group I (control): rats received normal saline...
May 25, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28542097/genome-wide-association-and-pathway-analysis-of-left-ventricular-function-after-anthracycline-exposure-in-adults
#6
Quinn S Wells, Olivia J Veatch, Joshua P Fessel, Aron Y Joon, Rebecca T Levinson, Jonathan D Mosley, Elizabeth P Held, Chase S Lindsay, Christian M Shaffer, Peter E Weeke, Andrew M Glazer, Kevin R Bersell, Sara L Van Driest, Jason H Karnes, Marcia A Blair, Lore W Lagrone, Yan R Su, Erica A Bowton, Ziding Feng, Bonnie Ky, Daniel J Lenihan, Michael J Fisch, Joshua C Denny, Dan M Roden
BACKGROUND: Anthracyclines are important chemotherapeutic agents, but their use is limited by cardiotoxicity. Candidate gene and genome-wide studies have identified putative risk loci for overt cardiotoxicity and heart failure, but there has been no comprehensive assessment of genomic variation influencing the intermediate phenotype of anthracycline-related changes in left ventricular (LV) function. The purpose of this study was to identify genetic factors influencing changes in LV function after anthracycline chemotherapy...
May 24, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28540470/effects-of-remifentanil-pretreatment-on-bupivacaine-cardiotoxicity-in-rats
#7
Özcan Pişkin, Hilal Ayoğlu
Unintentional intravascular administration of bupivacaine may cause local anesthetic systemic toxicity (LAST). Although many systems are affected in LAST, the cardiovascular effects can be life-threatening. Remifentanil is a selective, ultra-short-acting, µ-opioid receptor agonist opioid. This study assessed the effects of combined pretreatment with intravenous lipid emulsion (ILE) and remifentanil on the cardiotoxicity caused by bupivacaine in an experimental model of anesthetized rats. The rats were divided into three groups...
May 24, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28539089/simulating-real-life-exposures-to-uncover-possible-risks-to-human-health-a-proposed-consensus-for-a-novel-methodological-approach
#8
A M Tsatsakis, D Kouretas, M N Tzatzarakis, P Stivaktakis, K Tsarouhas, K S Golokhvast, V N Rakitskii, V A Tutelyan, A F Hernandez, R Rezaee, G Chung, C Fenga, A B Engin, M Neagu, A L Arsene, A O Docea, E Gofita, D Calina, I Taitzoglou, J Liesivuori, A W Hayes, S Gutnikov, C Tsitsimpikou
In real life, consumers are exposed to complex mixtures of chemicals via food, water and commercial products consumption. Since risk assessment usually focuses on individual compounds, the current regulatory approach doesn't assess the overall risk of chemicals present in a mixture. This study will evaluate the cumulative toxicity of mixtures of different classes of pesticides and mixtures of different classes of pesticides together with food additives (FAs) and common consumer product chemicals using realistic doses after long-term exposure...
June 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28537988/prevention-of-trastuzumab-and-anthracycline-induced-cardiotoxicity-using-angiotensin-converting-enzyme-inhibitors-or-%C3%AE-blockers-in-older-adults-with-breast-cancer
#9
Saranrat Wittayanukorn, Jingjing Qian, Salisa C Westrick, Nedret Billor, Brandon Johnson, Richard A Hansen
PURPOSE: Although clinical trials have provided some data on the benefit of angiotensin-converting enzyme inhibitors (ACEIs) or β-blockers (BBs) in patients with chemotherapy-induced cardiotoxicity, evidence of ACEIs/BBs on prevention of trastuzumab and/or anthracycline-induced cardiotoxicity outside trials is limited. MATERIALS AND METHODS: A cohort study of 142,990 women (66 y and above) newly diagnosed with breast cancer from 2001 to 2009 was conducted using the Surveillance, Epidemiology, and End Results-Medicare-linked database...
May 23, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28536660/sorafenib-associated-heart-failure-complicated-by-cardiogenic-shock-after-treatment-of-advanced-stage-hepatocellular-carcinoma-a-clinical-case-discussion
#10
Candace Wu, Kamal Shemisa
Background. Sorafenib, an oral tyrosine kinase inhibitor (TKI), targets multiple tyrosine kinase receptors (TKRs) involved in angiogenesis and tumor growth. Studies suggest that inhibition of TKR impacts cardiomyocyte survival. Inhibition of VEGF signaling interrupts angiogenesis and is associated with the development of hypertension and compensatory hypertrophy. Compensated hypertrophy ultimately leads to heart failure. Case Description. A 76-year-old man with a past medical history of systolic heart failure due to ischemic cardiomyopathy and stage IIIC hepatocellular carcinoma (HCC) presented with symptoms of decompensated heart failure...
2017: Case Reports in Cardiology
https://www.readbyqxmd.com/read/28536247/circadian-networks-in-human-embryonic-stem-cell-derived-cardiomyocytes
#11
Pieterjan Dierickx, Marit W Vermunt, Mauro J Muraro, Menno P Creyghton, Pieter A Doevendans, Alexander van Oudenaarden, Niels Geijsen, Linda W Van Laake
Cell-autonomous circadian oscillations strongly influence tissue physiology and pathophysiology of peripheral organs including the heart, in which the circadian clock is known to determine cardiac metabolism and the outcome of for instance ischemic stress. Human pluripotent stem cells represent a powerful tool to study developmental processes in vitro, but the extent to which human embryonic stem (ES) cell-derived cardiomyocytes establish circadian rhythmicity in the absence of a systemic context is unknown...
May 23, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28536214/safe-administration-of-s-1-after-5-fluorouracil-induced-cardiotoxicity-in-a-patient-with-colorectal-cancer
#12
Caspar Franck, Peter Malfertheiner, Marino Venerito
Cardiotoxicity is a rare but challenging complication of 5-fluorouracil (5-FU) therapy. Compared with 5-FU, after application of S-1 lower plasma levels of the cardiotoxic metabolite alpha-fluoro-beta-alanine have been reported. Evidence for safe administration of S-1 following 5-FU cardiotoxicity is limited to a case report in an Asian patient. Herein we report the first case of S-1 application after 5-FU cardiotoxicity in a Caucasian patient.A 67-year-old man with right-sided metastatic colorectal cancer and history of 5-FU cardiotoxicity had a progressive disease after 8-month therapy with irinotecan and bevacizumab...
May 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28532082/ultrasonic-nanotherapy-of-breast-cancer-using-novel-ultrasound-responsive-alginate-shelled-perfluorohexane-nanodroplets-in-vitro-and-in-vivo-evaluation
#13
Fatemeh Baghbani, Mahdieh Chegeni, Fathollah Moztarzadeh, Jamshid Aghazadeh Mohandesi, Manijhe Mokhtari-Dizaji
Development of a new class of multifunctional ultrasound-responsive smart nanocarriers that combine therapeutic properties with diagnostic imaging has gained great attention in recent years. Here, we describe the results of ultrasonic nanotherapy of breast cancer using novel alginate-stabilized perfluorohexane nanodroplets. Doxorubicin (Dox)-loaded multifunctional nanodroplets (Dox-NDs) were synthesized via nanoemulsion process and evaluated in vitro and in vivo with focus on cytotoxicity, hemolytic activity, biodistribution, biosafety, and antitumor activity...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28531339/limtox-a-web-tool-for-applied-text-mining-of-adverse-event-and-toxicity-associations-of-compounds-drugs-and-genes
#14
Andres Cañada, Salvador Capella-Gutierrez, Obdulia Rabal, Julen Oyarzabal, Alfonso Valencia, Martin Krallinger
A considerable effort has been devoted to retrieve systematically information for genes and proteins as well as relationships between them. Despite the importance of chemical compounds and drugs as a central bio-entity in pharmacological and biological research, only a limited number of freely available chemical text-mining/search engine technologies are currently accessible. Here we present LimTox (Literature Mining for Toxicology), a web-based online biomedical search tool with special focus on adverse hepatobiliary reactions...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531278/cardiovascular-toxic-effects-of-targeted-cancer-therapy
#15
Kazuko Tajiri, Kazutaka Aonuma, Ikuo Sekine
Over the past decade, there has been a major shift in chemotherapy from non-specific cytotoxic drugs to molecular targeted drug therapies. As more molecular targeted therapies are developed, new types of cardiovascular toxicities induced by targeted therapies are a growing problem. Cardiotoxicity induced by the human epidermal growth factor receptor-2 inhibitor trastuzumab manifests as decreased left ventricular ejection fraction. In contrast to anthracycline treatment, most cardiac events occur during trastuzumab treatment, but are reversed quickly when treatment is interrupted and cardiac intervention is established...
May 20, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28531112/effects-of-polyphenols-on-oxidative-stress-mediated-injury-in-cardiomyocytes
#16
REVIEW
Rosanna Mattera, Monica Benvenuto, Maria Gabriella Giganti, Ilaria Tresoldi, Francesca Romana Pluchinotta, Sonia Bergante, Guido Tettamanti, Laura Masuelli, Vittorio Manzari, Andrea Modesti, Roberto Bei
Cardiovascular diseases are the main cause of mortality and morbidity in the world. Hypertension, ischemia/reperfusion, diabetes and anti-cancer drugs contribute to heart failure through oxidative and nitrosative stresses which cause cardiomyocytes nuclear and mitochondrial DNA damage, denaturation of intracellular proteins, lipid peroxidation and inflammation. Oxidative or nitrosative stress-mediated injury lead to cardiomyocytes apoptosis or necrosis. The reactive oxygen (ROS) and nitrogen species (RNS) concentration is dependent on their production and on the expression and activity of anti-oxidant enzymes...
May 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28526544/interleukin-18-gene-deletion-protects-against-sepsis-induced-cardiac-dysfunction-by-inhibiting-pp2a-activity
#17
Yoshitaka Okuhara, Shunichi Yokoe, Toshihiro Iwasaku, Akiyo Eguchi, Koichi Nishimura, Wen Li, Makiko Oboshi, Yoshiro Naito, Toshiaki Mano, Michio Asahi, Haruki Okamura, Tohru Masuyama, Shinichi Hirotani
BACKGROUND: Interleukin-18 (IL-18) neutralization protects against lipopolysaccharide (LPS)-induced injuries, including myocardial dysfunction. However, the mechanism is yet to be fully elucidated. The aim of the present study was to determine whether IL-18 gene deletion prevents sepsis-induced cardiac dysfunction and to elucidate the potential mechanisms underlying IL-18-mediated cardiotoxicity by LPS. METHODS AND RESULTS: Ten-week-old male wild-type (WT) and IL-18 knockout (IL-18 KO) mice were intraperitoneally administered LPS...
May 4, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28525371/arsenic-trioxide-and-angiotensin-ii-have-inhibitory-effects-on-herg-protein-expression-evidence-for-the-role-of-pml-sumoylation
#18
Yu Liu, Duo Li, Dan Nie, Shang-Kun Liu, Fang Qiu, Mei-Tong Liu, Yuan-Yuan Li, Jia-Xin Wang, Yan-Xin Liu, Chang-Jiang Dong, Di Wu, Wei Tian, Jia Yang, Wei Mu, Jia-Tong Li, Dan Zhao, Xiao-Feng Wang, Wen-Feng Chu, Bao-Feng Yang
The human ether-a-go-go-related gene (HERG) channel is a novel target for the treatment of drug-induced long QT syndrome, which causes lethal cardiotoxicity. This study is designed to explore the possible role of PML SUMOylation and its associated nuclear bodies (NBs) in the regulation of HERG protein expression. Both arsenic trioxide (ATO) and angiotensin II (Ang II) were able to significantly reduce HERG protein expression, while also increasing PML SUMOylation and accelerating the formation of PML-NBs. Pre-exposure of cardiomyocytes to a SUMOylation chemical inhibitor, ginkgolic acid, or the silencing of UBC9 suppressed PML SUMOylation, subsequently preventing the downregulation of HERG induced by ATO or Ang II...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525367/liposomal-co-delivered-oleanolic-acid-attenuates-doxorubicin-induced-multi-organ-toxicity-in-hepatocellular-carcinoma
#19
Muhammad Sarfraz, Attia Afzal, Shahid Masood Raza, Sajid Bashir, Asadullah Madni, Muhammad Waseem Khan, Xiang Ma, Guangya Xiang
Doxorubicin in combination with other cytotoxic drugs has clinical advantages. However, doxorubicin-induced cardiotoxicity negatively impacts clinical utility and outcomes. Cardiotoxicity can result from increased oxidative stress or from a local cytochrome P450 mediated increase in 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE). Oleanolic acid (OA) is a natural pentacyclic triterpenoid with free radical scavenging, cardioprotective, and P450-mediated cyclooxygenase-upregulating properties. We investigated co-delivery of liposomal OA and doxorubicin in a HepG2 model of hepatocellular carcinoma (HCC)...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28521615/comprehensive-evaluation-of-usnic-acid-induced-cardiotoxicity-in-rats-by-sequential-cross-omics-analysis
#20
Y Yokouchi, M Imaoka, N Niino, N Kiyosawa, K Kai
Two-week administration of (+)-usnic acid (UA) induces mitochondrial swelling of cardiomyocytes, and toxicogenomic analysis of the heart revealed upregulation of oxidative stress, amino acid limitation, and endoplasmic reticulum stress-related genes in rats. To analyze the pathogenesis, UA was orally administrated to rats for 1, 4, 7, and 14 days, and sequential histopathological, genomic, and metabolomic analyses were performed on the heart, liver, and plasma. As a result, mitochondrial swelling of cardiomyocytes was observed on day 15 preceded by genomic upregulation on days 5 and 8...
January 1, 2017: Toxicologic Pathology
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