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Cardiovascular Toxicology

Sule Ozbilgin, Derya Aslan Yurtlu, Beyza Küçükoztaş, Gonca Kamacı, Sezen Korkut, Bülent Serhan Yurtlu, M Ensari Güneli, Volkan Hancı, Ali Günerli
Previous studies have shown that cyclodextrin group medicines bind to various drugs. The hypothesis of our study is to determine whether sugammadex could bind to digoxin and delay the cardiovascular toxicity of that drug. Twenty-eight sedated Wistar rats were infused with digoxin at 3 mg/h (0.25 mg/ml). Five minutes after the start of infusion, animals were treated with a bolus of either 16 mg/kg (Sgdx16), 100 mg/kg (Sgdx100), or 1000 mg/kg (Sgdx1000) sugammadex. The control group infusion did not contain sugammadex...
March 16, 2018: Cardiovascular Toxicology
Su Tu, Feng Xiao, Xiaoyan Min, Huiping Chen, Xiaochun Fan, Kejiang Cao
Accumulating evidence has established that systemic inflammation is an important pathophysiologic factor of coronary heart disease (CHD). In this study, we investigated whether catechin exerts anti-inflammatory function in CHD rats. CHD model of rats was established by high-fat diet feeding and pituitrin injection. The successful building of CHD model was confirmed using blood liquid biochemical analyzer. Additionally, the effects of catechin on CHD parameters and several inflammatory signaling were investigated...
February 20, 2018: Cardiovascular Toxicology
Cansu Arslan Turan, Tuba Cimilli Ozturk, Ebru Unal Akoglu, Rohat Ak, Kemal Aygun, Ali Sahiner, Engin Sumer, Adnan Somay, Ozge Ecmel Onur
Although the mechanism of action is not well known, intravenous lipid emulsion (ILE) has been shown to be effective in the treatment of lipophilic drug intoxications. It is thought that, ILE probably separates the lipophilic drugs from target tissue by creating a lipid-rich compartment in the plasma. The second theory is that ILE provides energy to myocardium with high-dose free fatty acids activating the voltage-gated calcium channels in the myocytes. In this study, effects of ILE treatment on digoxin overdose were searched in an animal model in terms of cardiac side effects and survival...
February 3, 2018: Cardiovascular Toxicology
Wen Yin, Rui Li, Xiaorong Feng, Y James Kang
Cytochrome c oxidase (CCO) is a copper-dependent enzyme of mitochondrial respiratory chain. In pressure overload-induced cardiac hypertrophy, copper level and CCO activity are both depressed, along with disturbance in mitochondrial fusion and fission dynamics. Copper repletion leads to recovery of CCO activity and normalized mitochondrial dynamics. The present study was undertaken to define the link between CCO activity and mitochondrial dynamic changes. Primary cultures of neonatal rat cardiomyocytes were treated with phenylephrine to induce cell hypertrophy...
February 2, 2018: Cardiovascular Toxicology
Narges-Sadat Zahed, Hossein Hassanian-Moghaddam, Nasim Zamani
Using calcium salts in management of amlodipine overdose is challenging. A 25-year-old male with known history of adult polycystic kidney disease presented with hypotension, tachycardia, and intact neurological status after ingestion of 450 mg of amlodipine. Immediately, normal saline infusion and norepinephrine were initiated. Two grams of calcium gluconate was injected, followed by intravenous infusion of 1.16 mg/kg/h. The patient was put on insulin-glucose protocol to maintain euglycemia and hyperinsulinemia...
January 30, 2018: Cardiovascular Toxicology
Mehdi Goudarzi, Iman Fatemi, Amir Siahpoosh, Seyed Hashem Sezavar, Esrafil Mansouri, Saeed Mehrzadi
Ellagic acid (EA) is a phenolic constituent in certain fruits and nuts with wide range of biological activities, including potent antioxidant, antidiabetic, anti-inflammatory, anticancer and antimutagen properties. The aim of this study was to evaluate the effect of EA on sodium arsenic (SA)-induced cardio- and hematotoxicity in rats. Animals were divided into five groups. The first group was used as control. Group 2 was orally treated with sodium arsenite (SA, 10 mg/kg) for 21 days. Group 3 was orally treated with EA (30 mg/kg) for 14 days...
January 30, 2018: Cardiovascular Toxicology
Jitka Skrabalova, Ivana Karlovska, Lucie Hejnova, Jiri Novotny
There are some indications that morphine may exert myocardial protective effects under certain conditions. The aim of the present study was to investigate the effect of morphine on viability and oxidative state of H9c2 cells (rat cardiomyoblasts) influenced by oxidative stress that was elicited by exposure to tert-butyl hydroperoxide (t-BHP). Our experiments showed that pretreatment with morphine before the addition of t-BHP markedly improved cell viability. Morphine was able to increase total antioxidant capacity of H9c2 cells and to reduce the production of reactive oxygen species, protein carbonylation, and lipid peroxidation...
January 29, 2018: Cardiovascular Toxicology
Kamal Gupta, Rishi Sharma, Vikas Singh, Reza Masoomi, Kottarappat N Dileepan, Jianghua He, Donald D Smith, Buddhadeb Dawn, Kenneth Grasing
Cocaine use causes significant cardiovascular morbidity from its hemodynamic effects. It is less clear whether cocaine promotes atherosclerosis. Vascular inflammation is one of the earliest steps in the pathophysiology of atherosclerosis. We hypothesized that cocaine results in an increase in inflammatory markers. Study objective was to measure the acute effects of intravenous cocaine on biomarkers of vascular inflammation. Eleven chronic cocaine users were enrolled. After a drug-free period, they received intravenous cocaine at 0...
January 25, 2018: Cardiovascular Toxicology
Anamika Vishwakarma, Thakur Uttam Singh, Soya Rungsung, Tarun Kumar, Arunvikram Kandasamy, Subhashree Parida, Madhu Cholenahalli Lingaraju, Ajay Kumar, Asok Kumar, Dinesh Kumar
The present study was undertaken to evaluate the effect of kaempferol in isoprenaline (ISP)-induced myocardial injury in rats. ISP was administered subcutaneously for two subsequent days to induce myocardial injury. Assessment of myocardial injury was done by estimation of hemodynamic functions, myocardial infarcted area, cardiac injury markers, lipid profile, oxidative stress, pro-inflammatory cytokines and histopathology of heart and liver. Rats pretreated with kaempferol showed reduction in the myocardial infarcted area and heart rate...
January 20, 2018: Cardiovascular Toxicology
Yu-Ting Chung, Che-Yi Chou, Wen-Chen Tsai, Wei-Kung Chen, Cheng-Li Lin, Wei-Sheng Chung
The purpose of this nationwide cohort study was to investigate the incidence and risk of coronary artery disease (CAD) in patients with acetaminophen (APAP) poisoning. We identified the patients with APAP poisoning and randomly selected comparison patients according to a 1:4 ratio, matching them by age, sex, and the index year using data from the National Health Insurance Research Database from 2000 to 2010. We traced both cohorts until a diagnosis of CAD, loss to follow-up, or the end of 2011. In total, 2723 patients with APAP poisoning and 10,892 comparison patients have followed...
January 4, 2018: Cardiovascular Toxicology
Liping Zhang, Qiming Feng, Teng Wang
Paraquat is a highly toxic prooxidant that triggers oxidative stress and multi-organ failure including that of the heart. To date, effective treatment of paraquat toxicity is still not established. Necroptosis, a newly discovered form of programmed cell death, was recently shown to be strongly associated with cardiovascular disease. Receptor interaction proteins 1 (RIP1), receptor interaction proteins 3 (RIP3), and mixed lineage kinase domain like (MLKL) are key proteins in the necroptosis pathway. Necrostatin-1 (Nec-1) is a specific inhibitor of necroptosis which acts by blocking the interaction between RIP1 and RIP3...
January 3, 2018: Cardiovascular Toxicology
Nur Jaharat Lubna, Takeshi Wada, Yuji Nakamura, Koki Chiba, Xin Cao, Hiroko Izumi-Nakaseko, Kentaro Ando, Atsuhiko T Naito, Yoshioki Satoh, Atsushi Sugiyama
Amitriptyline has been reported to induce long QT syndrome in addition to Brugada syndrome. We qualitatively and quantitatively analyzed the potential of amitriptyline to induce these lethal syndromes by using the halothane-anesthetized dogs (n = 6). Amitriptyline was intravenously administered in doses of 0.1, 1 and 10 mg/kg over 10 min every 20 min, which would provide approximately 1, 10 and 100 times higher plasma concentrations than a therapeutic one, respectively. The low dose hardly altered any of the cardiovascular variables...
February 2018: Cardiovascular Toxicology
Melissa Mariana, Joana Feiteiro, Elisa Cairrao
Phthalates are one of the main constituents of plastic, reaching up to 40% of the total plastic weight, and their main function is to impart flexibility/elasticity to polymers that would otherwise be rigid. Phthalates are known as endocrine disruptors, since they can interfere with hormone homeostasis. Regarding the cardiovascular system, it was already shown the effects of di-(2-ethylhexyl) phthalate (DEHP) exposure with significant changes in several calcium-handling proteins and an increase in the blood pressure of mice offspring, suggesting that DEHP leads to vasocontraction...
December 8, 2017: Cardiovascular Toxicology
Ying Xiao, Yinjie Liu, Jiaming Liu, Y James Kang
Myocardial fibrogenesis is initiated once the coordination between oxygen supply and demand is disrupted in pressure overload-induced cardiac hypertrophy. Clinical observations showed that myocardial fibrosis did not evenly occur in the hypertrophic myocardium. The present study was undertaken to specifically address differential vulnerabilities to fibrogenesis of different regions in the myocardium subjected to pressure overload-induced hypertrophy. SD rats were divided into two groups, sham-operated control and ascending artery constriction-induced cardiac hypotrophy...
December 4, 2017: Cardiovascular Toxicology
Zaid H Maayah, Ghada Abdelhamid, Osama H Elshenawy, Ahmed A El-Sherbeni, Hassan N Althurwi, Erica McGinn, Doaa Dawood, Ahmad H Alammari, Ayman O S El-Kadi
Several studies have demonstrated the role of cytochrome P450 (CYP) and its associated arachidonic acid (AA) metabolites in the anthracyclines-induced cardiac toxicity. However, the ability of daunorubicin (DNR) to induce cardiotoxicity through the modulation of CYP and its associated AA metabolites has not been investigated yet. Therefore, we hypothesized that DNR-induced cardiotoxicity is mediated through the induction of cardiotoxic hydroxyeicosatetraenoic acids and/or the inhibition of cardioprotctive epoxyeicosatrienoic acids (EETs)...
December 1, 2017: Cardiovascular Toxicology
Ernest S Fung, Andrew Monnot, Michael Kovochich, Kenneth M Unice, Brooke E Tvermoes, David Galbraith, Brent L Finley, Dennis J Paustenbach
Over 300,000 hip replacements occurred in the USA in 2010, and the frequency is likely increasing annually. Blood Cobalt (Co) concentrations in patients with well-functioning cobalt-chromium (Co-Cr) hip implants are usually elevated above background concentrations relative to the general population. Excessive Co exposure, in rare cases, can result in cardiomyopathy. The purpose of this review was to identify cases of cardiomyopathy in metal-containing hip implant patients and to evaluate the possible cause of each patient's cardiomyopathy...
November 29, 2017: Cardiovascular Toxicology
Silvia Pulignani, Andrea Borghini, Cecilia Vecoli, Ilenia Foffa, Lamia Ait-Ali, Maria Grazia Andreassi
Recent experimental studies showed that ablation of the aryl hydrocarbon receptor (AhR) as well as its activation by exogenous ligands disrupt the molecular networks involved in heart formation and function, leading to congenital heart disease (CHD). However, no evidence is available about the role of AhR in humans. We assessed the prevalence of a functional AhR genetic variant (p.Arg554Lys) in CHD patients as well as its joint effects with parental exposure. A total of 128 CHD patients (76 males; age 6.2 ± 6...
November 28, 2017: Cardiovascular Toxicology
Yoshiyuki Motokawa, Yuji Nakamura, Mihoko Hagiwara-Nagasawa, Ai Goto, Koki Chiba, Nur Jaharat Lubna, Hiroko Izumi-Nakaseko, Kentaro Ando, Atsuhiko T Naito, Hiroshi Yamazaki, Atsushi Sugiyama
Anti-atrial fibrillatory, proarrhythmic and cardiodepressive profiles of dronedarone were analyzed using the halothane-anesthetized beagle dogs (n = 4) to create a standard protocol for clarifying both efficacy and adverse effects of anti-atrial fibrillatory drugs. Intravenous administration of dronedarone hydrochloride in doses of 0.3 and 3 mg/kg over 30 s attained the peak plasma concentrations of 61 and 1248 ng/mL, respectively, reflecting sub- to supra-therapeutic ones. The low dose decreased the left ventricular contraction and mean blood pressure, which were enhanced at the high dose...
November 14, 2017: Cardiovascular Toxicology
Sung Eun Shin, Hongliang Li, Jin Ryeol An, Mi Seon Seo, Sung Hun Na, Won-Kyo Jung, Amy L Firth, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Il-Whan Choi, Won Sun Park
We describe the effect of a tricyclic antidepressant drug desipramine on voltage-dependent K(+) (Kv) currents in freshly isolated rabbit coronary arterial smooth muscle cells using a conventional whole-cell patch clamp technique. Application of desipramine rapidly decreased the Kv current amplitude in a concentration-dependent manner, with an IC50 value of 5.91 ± 0.18 μM and a Hill coefficient of 0.61 ± 0.09. The steady-state inactivation curves of the Kv channels were not affected by desipramine. However, desipramine shifted the steady-state inactivation curves toward a more negative potential...
November 13, 2017: Cardiovascular Toxicology
Mai O Kadry, Rehab M Abdel-Megeed
Mesenchymal stem cells (MSCs) are multipotent stromal cells that merit the differentiation into various cell types. The present study was designed to test the hypothesis that the cardioprotective effect of MSCs transplantation and digoxin treatment is mediated via the regulation of messenger RNA gene expression of pro-inflammatory cytokines and apoptotic markers. Myocardial infarction was induced in Wistar rats via isoproterenol injection in a dose of (85 mg/kg, subcutaneously, twice at an interval of 24 h)...
November 6, 2017: Cardiovascular Toxicology
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