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Cardiac Toxicity

Arathi Kizhedath, Simon Wilkinson, Jarka Glassey
Biopharmaceuticals, monoclonal antibody (mAb)-based therapeutics in particular, have positively impacted millions of lives. MAbs and related therapeutics are highly desirable from a biopharmaceutical perspective as they are highly target specific and well tolerated within the human system. Nevertheless, several mAbs have been discontinued or withdrawn based either on their inability to demonstrate efficacy and/or due to adverse effects. Approved monoclonal antibodies and derived therapeutics have been associated with adverse effects such as immunogenicity, cytokine release syndrome, progressive multifocal leukoencephalopathy, intravascular haemolysis, cardiac arrhythmias, abnormal liver function, gastrointestinal perforation, bronchospasm, intraocular inflammation, urticaria, nephritis, neuropathy, birth defects, fever and cough to name a few...
October 20, 2016: Archives of Toxicology
Nasser Razmaraii, Hossein Babaei, Alireza Mohajjel Nayebi, Gholamreza Assadnassab, Javad Ashrafi Helan, Yadollah Azarmi
Purpose: The aim of the present study was to determine the ability of grape seed extract (GSE) as a powerful antioxidant in preventing adverse effect of doxorubicin (DOX) on heart function. Methods: Male rats were divided into three groups: control, DOX (2 mg/kg/48h, for 12 days) and GSE (100 mg/kg/24h, for 16 days) plus DOX. Left ventricular (LV) function and hemodynamic parameters were assessed using echocardiography, electrocardiography and a Millar pressure catheter. Histopathological analysis and in vitro antitumor activity were also evaluated...
September 2016: Advanced Pharmaceutical Bulletin
Kapil Suchal, Salma Malik, Nanda Gamad, Rajiv Kumar Malhotra, Sameer N Goyal, Jagriti Bhatia, Dharamvir Singh Arya
BACKGROUND: Myocardial infarction (MI) continues to be associated with high morbidity and mortality worldwide despite the availability of current therapeutic modalities. Kaempferol (KMP), a dietary flavonoid, possesses good antioxidant, immunomodulatory and anti-apoptotic properties and has been evaluated in the present study for its role in mitigating myocardial injury following MI. PURPOSE: In this study, the ability of KMP to protect heart against isoproterenol (ISO) induced oxidative stress and myocardial infarction was evaluated...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Işıl Bavunoğlu, Musa Balta, Zeynep Türkmen
BACKGROUND: There is an increasing interest in herbal products as a self-medication method in recent years. Some plant extracts either turn into drugs over time or are consumed directly without treatment. One of these plants is Nerium oleander L., which is a potentially lethal plant, since it has cardiac glycosides. However, numerous researches of its extracts have been performed against cancer cell lines in recent literature. This contradiction leads to misinterpretation and induces the prevalence of intoxication or fatal cases...
September 2016: Balkan Medical Journal
Paolo Spallarossa, Nicola Maurea, Christian Cadeddu, Rosalinda Madonna, Donato Mele, Ines Monte, Giuseppina Novo, Pasquale Pagliaro, Alessia Pepe, Carlo G Tocchetti, Concetta Zito, Giuseppe Mercuro
Anthracyclines are the mainstay of treatment of a variety of haematological malignancies and solid tumours. Unfortunately, the clinical use of these drugs is limited by cumulative, dose-related cardiotoxicity which may ultimately lead to a severe and irreversible form of cardiomyopathy. Thus, there is an increasing need for close cooperation among cardiologists, oncologists and haemato-oncologists. As anthracyclines save lives, the logical goal of this cooperation, besides preventing or mitigating cardiotoxicity, is to promote an acceptable balance between the potential cardiac side effects and the vital benefit of anticancer treatment...
May 2016: Journal of Cardiovascular Medicine
Nicola Maurea, Carmela Coppola, Giovanna Piscopo, Francesca Galletta, Gennaro Riccio, Emanuela Esposito, Claudia De Lorenzo, Michelino De Laurentiis, Paolo Spallarossa, Giuseppe Mercuro
The progress in cancer therapy and the increase in number of long-term survivors reveal the issue of cardiovascular side-effects of anticancer drugs. Cardiotoxicity has become a significant problem, and the risks of adverse cardiac events induced by systemic drugs need to be seriously considered. Potential cardiovascular toxicities linked to anticancer agents include arrhythmias, myocardial ischemia and infarction, hypertension, thromboembolism, left ventricular dysfunction, and heart failure. It has been shown that several anticancer drugs seriously affect the cardiovascular system, such as ErbB2 inhibitors, vascular endothelial growth factor (VEGF) inhibitors, multitargeted kinase inhibitors, Abelson murine leukemia viral oncogene homolog inhibitors, and others...
May 2016: Journal of Cardiovascular Medicine
Jason J Rose, Ling Wang, Qinzi Xu, Charles F McTiernan, Sruti Shiva, Jesus Tejero, Mark T Gladwin
Carbon monoxide (CO) poisoning affects 50,000 people a year in the United States. The clinical presentation runs a spectrum, ranging from headache and dizziness to coma and death, with a mortality rate ranging from 1-3%. A significant number of patients who survive CO poisoning suffer from long term neurologic and affective sequelae. The neurologic deficits do not necessarily correlate with blood CO levels, but likely result from the pleiotropic effects of CO on cellular mitochondrial respiration, cellular energy utilization, inflammation and free radical generation, especially in the brain and heart...
October 18, 2016: American Journal of Respiratory and Critical Care Medicine
Muhammad W Saif, Melissa Smith, Antonio Maloney
5-Fluorouracil (5-FU) is the backbone of the chemotherapy regimens approved for treatment of many malignancies, especially colorectal cancer (CRC). The incidence of cardiotoxicity associated with 5-FU ranges between 1.5% to 18% and is most commonly manifested as anginal symptoms. Cardiomyopathy is very rarely reported with 5-FU and capecitabine. A 35-year-old Caucasian male with T3, N1, M0 rectal cancer after the initial neoadjuvant chemoradiation with 5FU/LV followed by surgical abdominoperineal resection (APR), began mFOLFOX6 in the adjuvant setting...
September 14, 2016: Curēus
Patrick Amoateng, Samuel Adjei, Dorcas Osei-Safo, Believe Ahedor, Seidu A Mahmood, Benoit B N'guessan, Isaac J Asiedu-Gyekye, Alexander K Nyarko
BACKGROUND: Conflicting reports about the toxicity of Synedrella nodiflora (L) Gaertn (family Asteraceae), a plant traditionally used in Ghana for the management of epilepsy, abound in literature. The present study evaluates the effect of a 90-day continuous oral administration of a hydro-ethanolic whole plant extract of Synedrella nodiflora (SNE) in male Sprague-Dawley rats. METHODS: The toxicological evaluation of the extract (100, 300 and 1000 mgkg(-1)) was focused on haematological, serum biochemical parameters and histopathological changes of some isolated organs...
September 2016: Ghana Medical Journal
Maude St-Onge, Kurt Anseeuw, Frank Lee Cantrell, Ian C Gilchrist, Philippe Hantson, Benoit Bailey, Valéry Lavergne, Sophie Gosselin, William Kerns, Martin Laliberté, Eric J Lavonas, David N Juurlink, John Muscedere, Chen-Chang Yang, Tasnim Sinuff, Michael Rieder, Bruno Mégarbane
OBJECTIVE: To provide a management approach for adults with calcium channel blocker poisoning. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: Following the Appraisal of Guidelines for Research & Evaluation II instrument, initial voting statements were constructed based on summaries outlining the evidence, risks, and benefits. DATA SYNTHESIS: We recommend 1) for asymptomatic patients, observation and consideration of decontamination following a potentially toxic calcium channel blocker ingestion (1D); 2) as first-line therapies (prioritized based on desired effect), IV calcium (1D), high-dose insulin therapy (1D-2D), and norepinephrine and/or epinephrine (1D)...
October 3, 2016: Critical Care Medicine
Pavlína Hašková, Hana Jansová, Jan Bureš, Miloslav Macháček, Anna Jirkovská, Katherine J Franz, Petra Kovaříková, Tomáš Šimůnek
Catecholamines may undergo iron-promoted oxidation resulting in formation of reactive intermediates (aminochromes) capable of redox cycling and reactive oxygen species (ROS) formation. Both of them induce oxidative stress resulting in cellular damage and death. Iron chelation has been recently shown as a suitable tool of cardioprotection with considerable potential to protect cardiac cells against catecholamine-induced cardiotoxicity. However, prolonged exposure of cells to classical chelators may interfere with physiological iron homeostasis...
October 12, 2016: Toxicology
Christina K Speirs, Todd A DeWees, Sana Rehman, Alerson Molotievschi, Maria A Velez, Daniel Mullen, Sandra Fergus, Marco Trovo, Jeffrey D Bradley, Cliff G Robinson
INTRODUCTION: In the randomized trial of standard vs high dose chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (LA-NSCLC) (RTOG 0617), overall survival (OS) was worse in the high dose arm. While heart dose was suggested as a contributing factor, actionable parameters have not been established. We present an analysis of clinical and dosimetric parameters impacting OS in this patient population, focusing on heart dose. METHODS: Clinical data was collected on 416 patients with LA-NSLC treated at a single institution, with a subset of 333 available treatment plans re-contoured using RTOG normal tissue guidelines...
October 12, 2016: Journal of Thoracic Oncology
Jonathan A Edlow
Dizziness is a common chief complaint in emergency medicine. The differential diagnosis is broad and includes serious conditions, such as stroke, cardiac arrhythmia, hypovolemic states, and acute toxic and metabolic disturbances. Emergency physicians must distinguish the majority of patients who suffer from benign self-limiting conditions from those with serious illnesses that require acute treatment. Misdiagnoses are frequent and diagnostic test costs high. The traditional approach does not distinguish benign from dangerous causes and is not consistent with best current evidence...
November 2016: Emergency Medicine Clinics of North America
Xin Ming, Yuanming Feng, Chengwen Yang, Wei Wang, Ping Wang, Jun Deng
BACKGROUND: Radiation-induced heart disease (RIHD), which affects the patients' prognosis with both acute and late side effects, has been published extensively in the radiotherapy of breast cancer, lymphoma and other benign diseases. Studies on RIHD in lung cancer radiotherapy, however, are less extensive and clear even though the patients with lung cancer are delivered with higher doses to the heart during radiation treatment. METHODS: In this article, after extensive literature search and analysis, we reviewed the current evidence on RIHD in lung cancer patients after their radiation treatments and investigated the potential risk factors for RIHD as compared to other types of cancers...
October 2016: Medicine (Baltimore)
Xiao-Qiang Li, Xiao-Xiao Liu, Xue-Ying Wang, Yan-Hua Xie, Qian Yang, Xin-Xin Liu, Yuan-Yuan Ding, Wei Cao, Si-Wang Wang
The chemical property of cinnamaldehyde is unstable in vivo, although early experiments have shown its obvious therapeutic effects on viral myocarditis (VMC). To overcome this problem, we used cinnamaldehyde as a leading compound to synthesize derivatives. Five derivatives of cinnamaldehyde were synthesized: 4-methylcinnamaldehyde (1), 4-chlorocinnamaldehyde (2), 4-methoxycinnamaldehyde (3), α-bromo-4-methylcinnamaldehyde (4), and α-bromo-4-chlorocinnamaldehyde (5). Neonatal rat cardiomyocytes and HeLa cells infected by coxsackievirus B3 (CVB3) were used to evaluate their antiviral and cytotoxic effects...
October 17, 2016: Biomolecules & Therapeutics
Vishal R Mali, Guodong Pan, Mandar Deshpande, Rajarajan A Thandavarayan, Jiang Xu, Xiao-Ping Yang, Suresh S Palaniyandi
Aldehyde dehydrogenase (ALDH) 2 is a mitochondrial isozyme of the heart involved in the metabolism of toxic aldehydes produced from oxidative stress. We hypothesized that hyperglycemia-mediated decrease in ALDH2 activity may impair mitochondrial respiration and ultimately result in cardiac damage. A single dose (65 mg/kg; i.p.) streptozotocin injection to rats resulted in hyperglycemia with blood glucose levels of 443 ± 9 mg/dl versus 121 ± 7 mg/dl in control animals, p<0.0001, N = 7-11. After 6 months of diabetes mellitus (DM) induction, the rats were sacrificed after recording the functionality of their hearts...
2016: PloS One
Ji Hye Park, Sung Hyun Choi, Hyungtae Kim, Seung Taek Ji, Woong Bi Jang, Jae Ho Kim, Sang Hong Baek, Sang Mo Kwon
Doxorubicin (DOXO) is widely used to treat solid tumors. However, its clinical use is limited by side effects including serious cardiotoxicity due to cardiomyocyte damage. Resident cardiac progenitor cells (hCPCs) act as key regulators of homeostasis in myocardial cells. However, little is known about the function of hCPCs in DOXO-induced cardiotoxicity. In this study, we found that DOXO-mediated hCPC toxicity is closely related to calcium-related autophagy signaling and was significantly attenuated by blocking mTOR signaling in human hCPCs...
October 9, 2016: International Journal of Molecular Sciences
Neha Atale, Sharad Saxena, J Grace Nirmala, R T Narendhirakannan, Sujata Mohanty, Vibha Rani
There exists a complex and multifactorial relationship between diabetes and cardiovascular disease. Hyperglycemia is an important factor imposing damage (glucose toxicity) on cardiac cell leading to diabetic cardiomyopathy. There are substantial clinical evidences on the adverse effects of conventional therapies in the prevention/treatment of diabetic cardiovascular complications. Currently, green-synthesized nanoparticles have emerged as a safe, efficient, and inexpensive alternative for therapeutic uses. The present study discloses the silver nanoparticle biosynthesizing capability and cardioprotective potential of Syzygium cumini seeds already reported to have antidiabetic properties...
October 12, 2016: Applied Biochemistry and Biotechnology
Torben Esser, Gerburg Keilhoff, Uwe Ebmeyer
OBJECTIVE: Our asphyxia cardiac arrest (ACA) rat model is well established. The original model was designed in the 1990(th) using halothane and nitrous oxide for pre-insult anesthesia. Because of its hepato-toxicity and its potential to induce severe liver failures, halothane is no longer used in clinical anesthesia for several years. In order to minimize the health risk for our laboratory staff as well as to keep the experimental settings of our model on a clinically oriented basis we decided to replace halothane by sevoflurane...
October 7, 2016: Brain Research
Osama M Ahmed, Hanaa I Fahim, Magdy W Boules, Heba Y Ahmed
The present study aims to assess the toxic effect of latex and ethanolic leaf extract of Calotropis procera (C. procera), in comparison to abamectin, on serum biomarkers of function and histological integrity of heart and testis in male albino rats. To achieve this aim, the albino rats were separately administered 1/20 and 1/10 of LD50 of C. procera latex, ethanolic C. procera leaf extract and abamectin respectively by oral gavage for 4 and 8 weeks. C. procera latex and leaf extract as well as abamectin markedly elevated the activities of serum CK-MB, AST and LDH at the two tested periods in a dose dependent manner...
2016: SpringerPlus
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