Abstract：
:The anticancer drug lapatinib (Tykerb) is a dual tyrosine kinase inhibitor targeting the HER2 (ERBB2) and EGFR (ERBB1, HER1) pathways that have been shown in clinical trials to display some cardiotoxicity. Because trastuzumab also targets HER2 receptors, the lapatinib/doxorubicin combination provides a good model to probe the mechanism of the increased cardiotoxicity caused by the concurrent use of trastuzumab and doxorubicin. Using a neonatal rat cardiac myocyte model, we have investigated the ability of lapatinib alone and in combination with doxorubicin to damage myocytes. Lapatinib treatment alone only slightly induced myocyte damage. However, doxorubicin-induced myocyte damage was greatly potentiated by the addition of nanomolar lapatinib concentrations. Lapatinib alone treatment decreased phosphorylated ERK (MAPK), which may have, in part, contributed to the increased myocyte damage. As measured by flow cytometry, lapatinib-treated myocytes displayed an increased accumulation of doxorubicin. As lapatinib is a strong inhibitor of several ATP-dependent ABC-type efflux transporters, this likely occurred because lapatinib blocked doxorubicin efflux, thereby increasing intracellular doxorubicin concentrations and, thus, increasing myocyte damage. These results suggest that the clinical use of concurrent doxorubicin and lapatinib should be approached with care due to the possibility of lapatinib increasing doxorubicin cardiotoxicity.
journal_name
Cardiovasc Toxicoljournal_title
Cardiovascular toxicologyauthors
Hasinoff BB,Patel D,Wu Xdoi
10.1007/s12012-012-9183-xsubject
Has Abstractpub_date
2013-03-01 00:00:00pages
33-47issue
1eissn
1530-7905issn
1559-0259journal_volume
13pub_type
杂志文章abstract：:Arsenic toxicity is one of the major environmental problems causing various diseases, cardiovascular disorders is one of them. Several epidemiological studies have shown that arsenic causes cardiac hypertrophy but the detailed molecular mechanism is to be studied yet. This study is designed to determine the molecules ...
journal_title：Cardiovascular toxicology
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abstract：:Oxidative stress plays an important role in the pathogenesis of hypertension. Epigallocatechin-3-O-gallate (EGCG) is the main polyphenol present in green tea and is known for its potent antioxidant and anti-inflammatory properties. In the present study, we hypothesize that EGCG attenuates oxidative stress in the parav...
journal_title：Cardiovascular toxicology
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更新日期：2016-07-01 00:00:00
abstract：:We made an attempt to evaluate/compare the cardioprotective activity of two different doses (50 and 100 mg/kg body weight, given orally for 30 consecutive days) of Egyptian sweet marjoram leaf powder (MLP) and marjoram leaf aqueous extract (MLE) against isoproterenol (ISO)-induced myocardial infarcted rats (150 mg/kg ...
journal_title：Cardiovascular toxicology
pub_type： 杂志文章
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journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1007/s12012-010-9092-9
更新日期：2011-03-01 00:00:00
abstract：:Heart failure is a common complication of doxorubicin (DOX) therapy. Previous studies have shown that DOX adversely impacts cardiac energy metabolism, and the ensuing energy deficiencies antedate clinical manifestations of cardiac toxicity. Brief exposure of cultured cardiomyocytes to DOX significantly decreases creat...
journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1007/s12012-014-9283-x
更新日期：2015-04-01 00:00:00
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journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1385/ct:6:3:199
更新日期：2006-01-01 00:00:00
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journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1007/s12012-011-9105-3
更新日期：2011-06-01 00:00:00
abstract：:Arsenic trioxide (As2O3) is used clinically in the management of acute promyelocytic leukemia, and the use of electrocardiogram (ECG) in this management is important as arsenic use may cause distortion of the electrical properties with its attendant sequel. We studied the effect of As2O3 on vasomotion in rat aortic ri...
journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1007/s12012-015-9312-4
更新日期：2016-01-01 00:00:00
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journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1007/s12012-008-9012-4
更新日期：2008-03-01 00:00:00
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journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1007/s12012-014-9255-1
更新日期：2014-12-01 00:00:00
abstract：:The present study was designed to evaluate the cardioprotective potential of water extract of rhizomes of Acorus gramineus (AGR) against isoproterenol (ISO)-induced myocardial infarction. Male pigs were orally administered with 250 or 500 mg/kg of AGR or with vehicle for 9 days, with concurrent subcutaneous injections...
journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1007/s12012-014-9243-5
更新日期：2014-06-01 00:00:00
abstract：:Coxsackievirus B3 (CVB3) induces myocarditis, especially in the immunodeficient or immature. To investigate whether CVB3 induced pronounced cardiomyopathy during the severe immune dysfunction of murine acquired immunodeficiency syndrome (AIDS), female C57BL/6 mice were infected with LP-BM5 retrovirus and then coinfect...
journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1385/ct:2:1:53
更新日期：2002-01-01 00:00:00
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journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1385/ct:5:1:001
更新日期：2005-01-01 00:00:00
abstract：:Tolerance to clinically important organic nitrates such as nitroglycerin (NTG) has been experimentally related to endothelial dysfunction and vascular oxidative stress. Anti-oxidant enzymes such as the glutathione-S-transferases GSTs) could potentially play a protective role in NTG tolerance. Our previous work showed ...
journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1385/ct:6:2:131
更新日期：2006-01-01 00:00:00
abstract：:The use of anthracycline anticancer drugs is limited by a cumulative, dose-dependent cardiac toxicity. Iron chelation has long been considered as a promising strategy to limit this unfavorable side effect, either by restoring the disturbed cellular iron homeostasis or by removing redox-active iron, which may promote a...
journal_title：Cardiovascular toxicology
pub_type： 杂志文章,评审
doi：10.1007/s12012-007-0020-6
更新日期：2007-01-01 00:00:00
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journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1007/s12012-014-9293-8
更新日期：2015-07-01 00:00:00
abstract：:Cardiac toxicity has been associated with HIV infection and exposure to nucleoside reverse transcriptase inhibitors (NRTIs), but the role of the latter in the development of cardiac disease of HIV-infected patients is uncertain. To investigate the cardiotoxicity of transplacentally administered zidovudine (AZT) or AZT...
journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1385/ct:4:2:133
更新日期：2004-01-01 00:00:00
abstract：:Grape seed proanthocyanidin extract (GSPE), a polyphenolic compound with antioxidant properties, may protect against cardiac ischemia and reperfusion injury. However, its potential toxicity at higher doses is unknown. The authors tested the effects of GSPE on reactive oxygen species (ROS) generation, cell survival, la...
journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1385/ct:3:4:331
更新日期：2003-01-01 00:00:00
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journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1007/s12012-013-9238-7
更新日期：2014-06-01 00:00:00
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journal_title：Cardiovascular toxicology
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doi：10.1007/s12012-020-09587-1
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journal_title：Cardiovascular toxicology
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doi：10.1007/s12012-020-09608-z
更新日期：2021-01-01 00:00:00
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journal_title：Cardiovascular toxicology
pub_type： 杂志文章,评审
doi：10.1007/s12012-014-9282-y
更新日期：2015-04-01 00:00:00
abstract：:Doxorubicin (Dox) is widely used in cancer therapy, but the clinical application is limited by its cardiotoxicity. The underlying mechanism of Dox-induced cardiotoxicity remains unclear. Present study aimed to evaluate the role of NLRP3 inflammasome in Dox-induced cardiotoxicity. The NLRP3 inflammasome was activated i...
journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1007/s12012-020-09576-4
更新日期：2020-10-01 00:00:00
abstract：:Our previous study described the cardioprotective effects of ellagic acid in an isoproterenol-induced myocardial infarction model. In this study, we are reporting the mechanism of protective action of ellagic acid with respect to apoptosis and mitochondrial respiratory enzymes. Ellagic acid (7.5 and 15 mg/kg) was admi...
journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1007/s12012-011-9138-7
更新日期：2012-03-01 00:00:00
abstract：:Complete understanding of the etiology underlying endothelial damage in preeclampsia (PE) remains deficient. Recent studies suggest that autoantibodies against angiotensin II AT1 receptors (AT1-AA) may affect vascular endothelial integrity. However, direct evidence demonstrating association between AT1-AA from preecla...
journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1007/s12012-013-9229-8
更新日期：2014-03-01 00:00:00
abstract：:This study investigated the effect of metyrosine against ketamine-induced cardiotoxicity in rats and compared the results with the effect of metoprolol. In this study, rats were divided into groups A, B and C. In group A, we investigated the effects of a single dose of metyrosine (150 mg/kg) and metoprolol (20 mg/kg) ...
journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1007/s12012-014-9301-z
更新日期：2015-10-01 00:00:00
abstract：:Acute cardiovascular poisoning is a major cause of adverse outcomes in poisoning emergencies. The prognostic validity of corrected QT (QTc) and dispersed QT (QTd) in these outcomes is still limited. The present study aimed to determine the risk factors of mortality, adverse cardiovascular events (ACVE), and intensive ...
journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1007/s12012-020-09629-8
更新日期：2021-01-05 00:00:00
abstract：:It has been suggested that prenatal exposure to cadmium may alter the cardiovascular function during adulthood. Using the left coronary artery ligation model of acute myocardial infarction, we studied the cardiac function of female adult offspring rats exposed to cadmium (30 ppm) during gestation. The cardiac ischemic...
journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1007/s12012-011-9139-6
更新日期：2012-03-01 00:00:00
abstract：:This study was aimed at determining the efficacy of epinephrine, followed by chest compressions, in producing a return of spontaneous circulation (ROSC) during cyanide (CN)- or hydrogen sulfide (H2S)-induced toxic cardiac pulseless electrical activity (PEA) in the rat. Thirty-nine anesthetized rats were exposed to eit...
journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1007/s12012-018-9454-2
更新日期：2018-10-01 00:00:00
abstract：:Erythromycin is an antibiotic that prolongs the QT-interval and causes Torsade de Pointes (TdP) by blocking the rapid delayed rectifying potassium current (IKr) without affecting either the slow delayed rectifying potassium current (IKs) or inward rectifying potassium current (IK1). Erythromycin exerts this effect in ...
journal_title：Cardiovascular toxicology
pub_type： 杂志文章
doi：10.1007/s12012-019-09532-x
更新日期：2019-12-01 00:00:00
