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Cardiovascular Toxicology

Yoichi Tanikawa, Mihoko Hagiwara-Nagasawa, Ryuichi Kambayashi, Ai Goto, Koki Chiba, Kumiko Kitta, Kiyotaka Hoshiai, Hiroko Izumi-Nakaseko, Atsuhiko T Naito, Atsushi Sugiyama
Fluvoxamine is a selective serotonin-reuptake inhibitor, of which IC50 values for serotonin- and noradrenaline-uptake process were reported to be 3.8 and 620 nmol/L, respectively, also known to directly inhibit cardiac Na+ , Ca2+ , and K+ channels. We characterized microminipig as a laboratory animal by analyzing fluvoxamine-induced cardiovascular and dermatological responses under halothane anesthesia. Fluvoxamine maleate was infused in doses of 0.1, 1, and 10 mg/kg over 10 min with a pause of 20 min (n = 4)...
February 8, 2019: Cardiovascular Toxicology
S B Fournier, S Kallontzi, L Fabris, C Love, P A Stapleton
Normal pregnancy outcome is accomplished, in part, by rapid and expansive physiological adaptations to the systemic circulation, the extent of which is specific to gestational day (GD) and anatomical location. Pregnancy-related hemodynamic changes in uterine placental blood flow stimulate compensatory vascular signaling and remodeling that begins early and continues throughout gestation. Exposure of the maternal environment to engineered nanomaterials (ENM) during pregnancy has been shown to impact health of the dam, fetus, and adult offspring; however, the consequences of specific temporal (gestational age) and spatial (vascular location) considerations are largely undetermined...
February 7, 2019: Cardiovascular Toxicology
Marwin Bannehr, Lena Löhr, Julia Gelep, Wilhelm Haverkamp, Wolf-Hagen Schunck, Maik Gollasch, Alexander Wutzler
Cardiac ischemia/reperfusion injury is associated with the formation and action of lipid mediators derived from polyunsaturated fatty acids. Among them, linoleic acid (LA) is metabolized to epoxyoctadecanoic acids (EpOMEs) by cytochrome P450 (CYP) epoxygenases and further to dihydroxyoctadecanoic acids (DiHOMEs) by soluble epoxide hydrolase (sEH). We hypothesized that EpOMEs and/or DiHOMEs may affect cardiac post-ischemic recovery and addressed this question using isolated murine hearts in a Langendorff system...
February 6, 2019: Cardiovascular Toxicology
Ai Goto, Mihoko Hagiwara-Nagasawa, Ryuichi Kambayashi, Koki Chiba, Hiroko Izumi-Nakaseko, Atsuhiko T Naito, Yasunari Kanda, Atsushi Sugiyama
dl-Sotalol which can block both K+ channel and ß-adrenoceptor has been shown to prolong the J-Tpeak c of electrocardiogram in beagle dogs but tended to shorten it in microminipigs, although the drug prolonged the QT interval in both animals under physiologically maintained experimental condition. In order to estimate how the changes in the J-Tpeak c in the normal hearts would be reflected in the pathologic hearts, we compared proarrhythmic effects of dl-sotalol by using proarrhythmia models of beagle dogs and microminipigs, of which atrioventricular node had been ablated > 2 months and 8-9 weeks before, respectively (n = 4 for each species)...
February 2, 2019: Cardiovascular Toxicology
Van K Ninh, Elia C El Hajj, Alan J Mouton, Jason D Gardner
Fetal alcohol syndrome (FAS) is the most severe condition of fetal alcohol spectrum disorders (FASD) and is associated with congenital heart defects. However, more subtle defects such as ventricular wall thinning and cardiac compliance may be overlooked in FASD. Our studies focus on the role of cardiac fibroblasts in the neonatal heart, and how they are affected by prenatal alcohol exposure (PAE). We hypothesize that PAE affects fibroblast function contributing to dysregulated collagen synthesis, which leads to cardiac dysfunction...
January 25, 2019: Cardiovascular Toxicology
Mohamed M Sayed-Ahmed, Badr I Alrufaiq, Ammar Alrikabi, Mashan L Abdullah, Mohamed M Hafez, Othman A Al-Shabanah
This study has been initiated to investigate whether sunitinib (SUN) alters the expression of key genes engaged in mitochondrial transport and oxidation of long chain fatty acids (LCFA), and if so, whether these alterations should be viewed as a mechanism of SUN-induced cardiotoxicity, and to explore the molecular mechanisms whereby carnitine supplementation could attenuate SUN-induced cardiotoxicity. Adult male Wister albino rats were assigned to one of the four treatment groups: Rats in group 1 received no treatment but free access to tap water for 28 days...
January 14, 2019: Cardiovascular Toxicology
Vadavanath Prabhakaran Vineetha, Kozhiparambil Gopalan Raghu
Arsenic trioxide (ATO) is among the first-line chemotherapeutic drugs used in oncological practice. It has shown substantial efficacy in treating patients with relapsed or refractory acute promyelocytic leukaemia. The clinical use of ATO is hampered due to cardiotoxicity and hence many patients are precluded from receiving this highly effective treatment. An alternative to this would be to use any drug that can ameliorate the cardiotoxic effects and allow exploiting the full therapeutic potential of ATO, with considerable impact on cancer therapy...
January 7, 2019: Cardiovascular Toxicology
J M Moon, B J Chun, Y S Cho, S M Lee
To assess myocardial injury related to acute carbon monoxide (CO) poisoning, serial troponin I is measured in patients not presenting with troponin I elevation. This retrospective study investigated whether parameters related to white blood cell (WBC) counts (total and differential WBC counts, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio) improved predictive accuracy for troponin I elevation (> 0.04 ng/ml) in patients not presenting with evidence of myocardial injury. Serial parameters, troponin I values, and clinical courses were collected in 241 patients...
January 4, 2019: Cardiovascular Toxicology
Daryl Sudasena, Dinu Valentin Balanescu, Teodora Donisan, Saamir Hassan, Nicolas Palaskas, Peter Kim, Kaveh Karimzad, Juan Lopez-Mattei, Salman Arain, K Lance Gould, Cezar Iliescu
The use of vascular endothelial growth factor inhibitors such as sorafenib is limited by a risk of severe cardiovascular toxicity. A 28-year-old man with acute myeloid leukemia treated with prednisone, tacrolimus, and sorafenib following stem cell transplantation presented with severe bilateral lower extremity claudication. The patient was discharged against medical advice prior to finalizing a cardiovascular evaluation, but returned 1 week later with signs suggestive of septic shock. Laboratory tests revealed troponin I of 12...
December 12, 2018: Cardiovascular Toxicology
Guo-Xing Wan, Lan Cheng, Hai-Lun Qin, Yun-Zhang Zhang, Ling-Yu Wang, Yong-Gang Zhang
The wide use of anthracyclines represented by doxorubicin (DOX) has benefited cancer patients, yet the clinical application is limited due to its cardiotoxicity. Although numerous evidences have supported a role of microRNAs (miRNAs) in DOX-induced myocardial damage, the exact etiology and pathogenesis remain largely obscure. In this study, we focused on the role of miR-15b-5p in DOX-induced cardiotoxicity. We employed a public miRNA and gene microarray to screen differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) in rat cardiomyocytes, and 33 DEMs including miR-15b-5p and 237 DEGs including Bmpr1a and Gata4 were identified...
December 7, 2018: Cardiovascular Toxicology
Zahra Akbari, Mansour Esmailidehaj, Ebrahim Avarand, Mehrdad Shariati, Khalil Pourkhalili
Previous studies show that anabolic steroids impair innate cardioprotective mechanisms. Here, we investigated the effect of supraphysiological doses of nandrolone on ischemic preconditioning (IPC) as a potent cardioprotective tool against ischemia reperfusion (IR) injury in rat hearts. Male Wistar rats in two experimental settings of sedentary and exercise-trained (60 min/day swimming, 5 days/week, for 8 weeks) were either pretreated with intramuscular injections of arachis oil (Arach, n = 16) as vehicle or nandrolone decanoate (ND, n = 8), 10 mg/kg/week, for 8 weeks...
December 7, 2018: Cardiovascular Toxicology
Sarunya Laovitthayanggoon, Catherine J Henderson, Claire McCluskey, Margaret MacDonald, Rothwelle J Tate, M Helen Grant, Susan Currie
Exposure to circulating cobalt (Co2+ ) in patients with metal-on-metal orthopaedic hip implants has been linked to cardiotoxicity but the underlying mechanism(s) remain undefined. The aim of the current study was to examine the effects of Co2+ on the heart in vivo and specifically on cardiac fibroblasts in vitro. Adult male rats were treated with CoCl2 (1 mg/kg) for either 7 days or 28 days. Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure Co2+ uptake into various organs of the body...
December 6, 2018: Cardiovascular Toxicology
Mi Seon Seo, Hongliang Li, Jin Ryeol An, In Duk Jung, Won-Kyo Jung, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Il-Whan Choi, Won Sun Park
This study investigated vildagliptin-induced vasodilation and its related mechanisms using phenylephrine induced precontracted rabbit aortic rings. Vildagliptin induced vasodilation in a concentration-dependent manner. Pretreatment with the large-conductance Ca2+ -activated K+ channel blocker paxilline, ATP-sensitive K+ channel blocker glibenclamide, and inwardly rectifying K+ channel blocker Ba2+ did not affect the vasodilatory effects of vildagliptin. However, application of the voltage-dependent K+ (Kv) channel inhibitor 4-aminopyridine significantly reduced the vasodilatory effects of vildagliptin...
December 5, 2018: Cardiovascular Toxicology
Christian Ellermann, Julian Wolfes, Dirk Puckhaber, Nils Bögeholz, Patrick Leitz, Philipp S Lange, Lars Eckardt, Gerrit Frommeyer
A post hoc analysis of the PALLAS trial suggested life-threatening interactions of digitalis and dronedarone. Thus, there is concern about an interplay between digitalis and other drugs that influence cardiac electrophysiology. We therefore investigated the interaction between digitalis and flecainide or ranolazine. Twenty-five rabbit hearts were Langendorff-perfused and treated with flecainide (2 µM, 12 hearts) or ranolazine (10 µM, 13 hearts). Infusion of flecainide prolonged mean action potential duration [APD90 , from 153 ms (interquartile range (IQR): 29...
December 4, 2018: Cardiovascular Toxicology
Habib Haybar, Saeid Shahrabi, Hadi Rezaeeyan, Reza Shirzad, Najmaldin Saki
Endothelial cells (ECs) are the innermost layer of blood vessels that play important roles in homeostasis and vascular function. However, recent evidence suggests that the onset of inflammation and the production of reactive oxygen species impair the function of ECs and are a main factor in the development of cardiovascular disease (CVD). In this study, we investigated the effects of inflammatory markers, oxidative stress, and treatment on ECs in CVD patients. This review article is based on the material obtained from PubMed up to 2018...
December 1, 2018: Cardiovascular Toxicology
Ewa Hryniewiecka, Jolanta Żegarska, Dorota Żochowska, Emilia Samborowska, Radosław Jaźwiec, Maciej Kosieradzki, Sławomir Nazarewski, Michał Dadlez, Leszek Pączek
Cardiovascular disease (CVD) remains one of the primary causes of death after kidney transplantation (KTX). Cyclosporine (CsA) metabolites may play a role in CVD. Metabolic ratio (MR) may be considered a measure of intra-individual differences of CsA metabolism. The study was aimed at analysis of associations of CVD with indices of CsA metabolism: MRs and dose-adjusted CsA concentrations (C/D and C/D/kg). The study was performed in the Department of Immunology, Transplant Medicine, and Internal Diseases of the Medical University of Warsaw and involved 102 KTX recipients...
November 23, 2018: Cardiovascular Toxicology
Gaurav Taneja, Akash Sud, Narayan Pendse, Bishnu Panigrahi, Ashish Kumar, Arun K Sharma
The endothelium is a thin innermost layer of flat cells which release various mediators including endothelin-1 (ET-1), prostanoids, von Willebrand factor (vWF) and endothelium-derived relaxing factor (EDRF; nitric oxide) to regulate vascular tone. Endothelial nitric oxide synthase (eNOS) is a key enzyme that generates nitric oxide (NO). NO maintains vascular homeostasis and cardiac functions by influencing major vascular protective properties such as anti-platelet, anti-proliferative, anti-migratory, antioxidant and anti-inflammatory action in vessels...
November 17, 2018: Cardiovascular Toxicology
Lifang Zhao, Li Zhang, Minghui Chen, Chuan Dong, Ruijin Li, Zongwei Cai
Exposure to fine particulate matter (PM2.5 ) increased the risks of cardiovascular diseases. PM2.5 -bound 1-nitropyrene (1-NP) and 9-nitroanthracene (9-NA) are released from the incomplete combustion of fossil fuels and derived from polycyclic aromatic hydrocarbons (PAHs). The toxicities of 1-NP and 9-NA are mainly reflected in their carcinogenicity and mutagenicity. However, studies of PM2.5 -bound 1-NP and 9-NA on the cardiac genotoxicity are limited so far. In this study, histopathology, DNA damage, DNA repair-related gene expression, and oxidative stress were investigated in the hearts of male Wistar rats exposed to PM2...
November 12, 2018: Cardiovascular Toxicology
Raphael Anakwue
Cardiovascular disease has maintained the unenviable position as the number one cause of death in the world. It is now clear that the traditional risk factors of cardiovascular disease are driven by primary factors like globalisation, urbanisation, industrialisation and agricultural practices. Pesticide use is an integral component of modern and improved agriculture. The abuse and misuse of these chemicals has caused significant poisoning worldwide and particularly in low- and middle-income countries where Africa belongs...
November 7, 2018: Cardiovascular Toxicology
Vida Naderi-Boldaji, Siyavash Joukar, Ali Noorafshan, Mohammad-Ali Bahreinipour
The present study was conducted to evaluate the effect of blood flow restriction (BFR) training on cardiac resistance to isoproterenol (ISO) induced heart injury in old rats and examined the hypothesis that BFR training may interfere with age-associated impairment of mitochondria by the inhibitory phosphorylation of GSK-3β at Ser9. Old male Wistar rats were divided into the following six groups: CTL (control), ISO (isoproterenol-treated), Sh + ISO (sham-operated plus ISO), BFR + ISO (blood flow restriction plus ISO), Sh-Ex + ISO (sham-operated subjected to exercise and ISO), and BFR-Ex + ISO (blood flow restriction along with exercise and ISO)...
November 7, 2018: Cardiovascular Toxicology
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