Involvement of ROS/NLRP3 Inflammasome Signaling Pathway in Doxorubicin-Induced Cardiotoxicity.

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 in the myocardium of Dox-treating (5 mg/kg, once every other day, cumulative dosage to 15 mg/kg and sacrificed after 2 days of last Dox injection) C57BL/6 mice as shown by the up-regulation of NLRP3 and Caspase-1 p20. Dox (1 μM for 48 h) induced the apoptosis of H9c2 cells and primary cardiomyocytes concomitantly with up-regulation of NLRP3, ASC and Caspase-1 p20 expressions, as well as the increased IL-1β secretion, suggesting the activation of NLRP3 inflammasome. These effects of Dox on H9c2 cells and primary cardiomyocytes can be reversed by MCC950, a specific inhibitor of NLRP3. In view of the key role of ROS on the Dox-induced cardiotoxicity, the relationship between ROS and NLRP3 was further investigated. The ROS level was increased in myocardium, H9c2 cells and primary cardiomyocytes after treating with Dox. Decreasing ROS level by NAC can inhibit the NLRP3 inflammasome activation, secretion of IL-1β and apoptosis in Dox-treating H9c2 cells and primary cardiomyocytes. Collectively, this study reveals a crucial role of ROS/NLRP3-associated inflammasome activation in Dox-induced cardiotoxicity, and NLRP3 inflammasome may represent a new therapeutic target for Dox-induced cardiotoxicity.

journal_name

Cardiovasc Toxicol

authors

Wei S,Ma W,Li X,Jiang C,Sun T,Li Y,Zhang B,Li W

doi

10.1007/s12012-020-09576-4

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

507-519

issue

5

eissn

1530-7905

issn

1559-0259

pii

10.1007/s12012-020-09576-4

journal_volume

20

pub_type

杂志文章
  • Selenium supplementation decreases coxsackievirus heart disease during murine AIDS.

    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

    authors: Sepúlveda RT,Zhang J,Watson RR

    更新日期:2002-01-01 00:00:00

  • Oleic Acid Protects from Arsenic-Induced Cardiac Hypertrophy via AMPK/FoxO/NFATc3 Pathway.

    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

    pub_type: 杂志文章

    doi:10.1007/s12012-019-09550-9

    authors: Samanta J,Mondal A,Saha S,Chakraborty S,Sengupta A

    更新日期:2020-06-01 00:00:00

  • High-dose testosterone propionate treatment reverses the effects of endurance training on myocardial antioxidant defenses in adolescent male rats.

    abstract::This study was aimed at evaluation of changes in activities of selected antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and contents of key nonenzymatic antioxidants (glutathione, protein thiol groups, and α- and γ-tocopherols) in the left heart ventricle of youn...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1007/s12012-011-9105-3

    authors: Sadowska-Krępa E,Kłapcińska B,Jagsz S,Sobczak A,Chrapusta SJ,Chalimoniuk M,Grieb P,Poprzęcki S,Langfort J

    更新日期:2011-06-01 00:00:00

  • Acute coronary artery injury in dogs following administration of CI-1034, an endothelin A receptor antagonist.

    abstract::The objective of this study was to characterize acute coronary artery injury evoked by the endothelin A receptor (ETAR) antagonist, CI-1034. Male dogs (n = 5) were intravenously administered CI-1034 at 120 mg/kg for 4 d. Control animals (n = 3) received vehicle. Macroscopically, drug-related hemorrhage was observed in...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1385/ct:6:1:25

    authors: McDuffie JE,Yu X,Sobocinski G,Song Y,Chupka J,Albassam M

    更新日期:2006-01-01 00:00:00

  • An Overview on Arsenic Trioxide-Induced Cardiotoxicity.

    abstract::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 rece...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章,评审

    doi:10.1007/s12012-018-09504-7

    authors: Vineetha VP,Raghu KG

    更新日期:2019-04-01 00:00:00

  • Effects of Remifentanil Pretreatment on Bupivacaine Cardiotoxicity in Rats.

    abstract::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 effec...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1007/s12012-017-9413-3

    authors: Pişkin Ö,Ayoğlu H

    更新日期:2018-02-01 00:00:00

  • Acylated Ghrelin Protects the Hearts of Rats from Doxorubicin-Induced Fas/FasL Apoptosis by Stimulating SERCA2a Mediated by Activation of PKA and Akt.

    abstract::This study investigated if the cardioprotective effect of acylated ghrelin (AG) against doxorubicin (DOX)-induced cardiac toxicity in rats involves inhibition of Fas/FasL-mediated cell death. It also investigated if such an effect is mediated by restoring Ca+2 homeostasis from the aspect of stimulation of SERCA2a rece...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1007/s12012-019-09527-8

    authors: Shati AA,Dallak M

    更新日期:2019-12-01 00:00:00

  • MDMA Induced Cardio-toxicity and Pathological Myocardial Effects: A Systematic Review of Experimental Data and Autopsy Findings.

    abstract::3,4-Methylenedioxymethamphetamine (MDMA), more commonly known as "ecstasy," is a semi-synthetic entactogenic phenylethylamine. In recent years it has gained popularity as a recreational drug whose use has registered an upward trend especially among adolescents and young adults. Despite its unwarranted reputation of be...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1007/s12012-019-09526-9

    authors: Bonsignore A,Barranco R,Morando A,Fraternali Orcioni G,Ventura F

    更新日期:2019-12-01 00:00:00

  • Mechanistic clues in the protective effect of ellagic acid against apoptosis and decreased mitochondrial respiratory enzyme activities in myocardial infarcted rats.

    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

    authors: Mari Kannan M,Darlin Quine S

    更新日期:2012-03-01 00:00:00

  • Clopidogrel Pharmacogenetics in Iranian Patients Undergoing Percutaneous Coronary Intervention.

    abstract::Clopidogrel is used in patients with coronary syndromes and at risk of thrombotic events or receiving percutaneous coronary intervention (PCI) for reducing heart attack and stroke. Here we present genotype and phenotype study of Iranian patients undergoing PCI treated with clopidogrel during a 6-month period of follow...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1007/s12012-018-9459-x

    authors: Mahdieh N,Rabbani A,Firouzi A,Zahedmehr A,Hoseinimoghaddam M,Saedi S,Sanati H,Basiri H,Noohi F,Rabbani B,Maleki M

    更新日期:2018-10-01 00:00:00

  • Cardioprotective effect of rhizomes of Acorus gramineus against isoproterenol-induced cardiac damage in pigs.

    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

    authors: Kim JH,Chung HS,Antonisamy P,Lee SR,Bae H

    更新日期:2014-06-01 00:00:00

  • Validation of Corrected and Dispersed QT as Predictors of Adverse Outcomes in Acute Cardiotoxicities.

    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

    authors: El-Sarnagawy GN,Shaban AE,Lashin HI

    更新日期:2021-01-05 00:00:00

  • The dual-targeted HER1/HER2 tyrosine kinase inhibitor lapatinib strongly potentiates the cardiac myocyte-damaging effects of doxorubicin.

    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 p...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1007/s12012-012-9183-x

    authors: Hasinoff BB,Patel D,Wu X

    更新日期:2013-03-01 00:00:00

  • eNOS deficient mice develop progressive cardiac hypertrophy with altered cytokine and calcium handling protein expression.

    abstract::Although studies have shown that endothelial nitric oxide synthase (eNOS) homozygous knockout mice (eNOS-/-) develop left ventricular (LV) hypertrophy, well compensated at least to 24 wks, uncertainty still exists as to the cardiac functional and molecular mechanistic consequences of eNOS deficiency at later time-poin...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1007/s12012-007-0028-y

    authors: Flaherty MP,Brown M,Grupp IL,Schultz JE,Murphree SS,Jones WK

    更新日期:2007-01-01 00:00:00

  • The Correlation Between 9p21 Chromosome rs4977574 Polymorphism Genotypes and the Development of Coronary Artery Heart Disease.

    abstract::Our aim is to investigate the correlation between 9p21 chromosome rs4977574 polymorphism genotypes and the development of coronary artery heart disease (CHD). Two hundred and eighty-nine patients with angiography-confirmed CHD were recruited as the CHD group, while 338 subjects without CHD symptoms were enrolled as th...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1007/s12012-016-9372-0

    authors: Tang O,Lv J,Cheng Y,Qin F

    更新日期:2017-04-01 00:00:00

  • Biokinetically-based in vitro cardiotoxicity of residual oil fly ash: hazard identification and mechanisms of injury.

    abstract::Epidemiological studies have associated air pollution particulate matter (PM) exposure with adverse cardiovascular effects. Identification of causal PM sources is critically needed to support regulatory decisions to protect public health. This research examines the in vitro cardiotoxicity of bioavailable constituents ...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1007/s12012-013-9225-z

    authors: Knuckles TL,Jaskot R,Richards JH,Miller CA,Ledbetter A,McGee J,Linak WP,Dreher KL

    更新日期:2013-12-01 00:00:00

  • Absence of mutation at the 5'-upstream promoter region of the TPM4 gene from cardiac mutant axolotl (Ambystoma mexicanum).

    abstract::Tropomyosins are a family of actin-binding proteins that show cell-specific diversity by a combination of multiple genes and alternative RNA splicing. Of the 4 different tropomyosin genes, TPM4 plays a pivotal role in myofibrillogenesis as well as cardiac contractility in amphibians. In this study, we amplified and se...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1007/s12012-011-9117-z

    authors: Denz CR,Zhang C,Jia P,Du J,Huang X,Dube S,Thomas A,Poiesz BJ,Dube DK

    更新日期:2011-09-01 00:00:00

  • Vildagliptin, an Anti-diabetic Drug of the DPP-4 Inhibitor, Induces Vasodilation via Kv Channel and SERCA Pump Activation in Aortic Smooth Muscle.

    abstract::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...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1007/s12012-018-9496-5

    authors: Seo MS,Li H,An JR,Jung ID,Jung WK,Ha KS,Han ET,Hong SH,Choi IW,Park WS

    更新日期:2019-06-01 00:00:00

  • Assessment of Safety Margin of an Antipsychotic Drug Haloperidol for Torsade de Pointes Using the Chronic Atrioventricular Block Dogs.

    abstract::Since an antipsychotic drug haloperidol has been clinically reported to induce QT interval prolongation and torsade de pointes, in this study its risk stratification for the onset of torsade de pointes was performed by using the chronic atrioventricular block canine model with a Holter electrocardiogram. Haloperidol i...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1007/s12012-016-9388-5

    authors: Izumi-Nakaseko H,Nakamura Y,Cao X,Wada T,Ando K,Sugiyama A

    更新日期:2017-07-01 00:00:00

  • Mammalian cardenolides as biomarkers in congestive heart failure.

    abstract::Congestive heart failure (CHF) afflicts over 5 million individuals in the United States, and most die within 5 yr of diagnosis. Because of the high morbidity and mortality associated with CHF, the search for biomarkers to predict, diagnose, and manage this disease has intensified. Calcium homeostasis and alterations i...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章,评审

    doi:10.1385/ct:1:2:165

    authors: Jortani SA,Valdes R Jr

    更新日期:2001-01-01 00:00:00

  • Manipulating glutathione-S-transferases may prevent the development of tolerance to nitroglycerin.

    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

    authors: Wang L,Yang Y,Dwivedi S,Xu Y,Chu ET,Li J,Fitchett K,Boor PJ

    更新日期:2006-01-01 00:00:00

  • Fresh gasoline emissions, not paved road dust, alter cardiac repolarization in ApoE-/- mice.

    abstract::Fresh vehicular emissions potentially represent a ubiquitous environmental concern for cardiovascular health. We compared electrocardiographic effects of fresh gasoline engine emissions with resuspended paved road dust in a mouse model of coronary insufficiency. Apolipoprotein E (ApoE)-/- mice on a high fat diet were ...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1385/ct:6:3:199

    authors: Campen MJ,McDonald JD,Reed MD,Seagrave J

    更新日期:2006-01-01 00:00:00

  • Distinct roles of p42/p44(ERK) and p38 MAPK in oxidant-induced AP-1 activation and cardiomyocyte hypertrophy.

    abstract::Cardiac hypertrophy is an adaptive response to a number of heart diseases including myocardial infarction. Although it can be compensatory at first, sustained hypertrophy is often a transition to heart failure. We have found that cardiomyocytes in culture can survive mild doses of H2O2 but develop hypertrophy involvin...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1385/ct:3:2:119

    authors: Tu VC,Bahl JJ,Chen QM

    更新日期:2003-01-01 00:00:00

  • Aryl hydrocarbon receptor null mice develop cardiac hypertrophy and increased hypoxia-inducible factor-1alpha in the absence of cardiac hypoxia.

    abstract::The aryl hydrocarbon receptor (AhR) is a member of the basic helix loop helix PAS (Per-ARNT-SIM) transcription family, which also includes hypoxiainducible factor-1alpha (HIF-1alpha) and its common dimerization partner AhR nuclear translocator (ARNT). Following ligand activation or hypoxia, AhR or HIF-1alpha, respecti...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1385/ct:2:4:263

    authors: Thackaberry EA,Gabaldon DM,Walker MK,Smith SM

    更新日期:2002-01-01 00:00:00

  • Atherosclerosis and cancer: flip sides of the neoplastic response in mammalian cells?

    abstract::Scientific and medical evidence over the past 30 years has established striking parallels between atherosclerosis and cancer--pathogenetic relationships that cross the boundaries of fiction into the realm of reason. Both diseases in humans are characterized by uncontrolled regulation of cellular growth and differentia...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章,评审

    doi:10.1385/ct:5:3:245

    authors: Ramos KS,Partridge CR

    更新日期:2005-01-01 00:00:00

  • On the Efficacy of Cardio-Pulmonary Resuscitation and Epinephrine Following Cyanide- and H2S Intoxication-Induced Cardiac Asystole.

    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

    authors: Judenherc-HaouzI A,Sonobe T,Bebarta VS,Haouzi P

    更新日期:2018-10-01 00:00:00

  • Epigenetic regulation of cardiac myofibril gene expression during heart development.

    abstract::Cardiac gene expression regulation is controlled not only by genetic factors but also by environmental, i.e., epigenetic factors. Several environmental toxic effects such as oxidative stress and ischemia can result in abnormal myofibril gene expression during heart development. Troponin, one of the regulatory myofibri...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1007/s12012-014-9278-7

    authors: Zhao W,Liu L,Pan B,Xu Y,Zhu J,Nan C,Huang X,Tian J

    更新日期:2015-07-01 00:00:00

  • Synchronization in the Heart Rate and the Vasomotion in Rat Aorta: Effect of Arsenic Trioxide.

    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

    authors: Cifuentes F,Palacios J,Nwokocha CR

    更新日期:2016-01-01 00:00:00

  • Preventive effect of total flavones of Choerospondias axillaries on ischemia/reperfusion-induced myocardial infarction-related MAPK signaling pathway.

    abstract::Choerospondias axillaris (Guangzao) is a medicinal plant used in Mongolia, and its fruit is commonly used for the treatment of cardiovascular diseases in clinic. The constituents responsible for this effect are always conceded to be the total flavonoids of C. axillaries (TFC). The present study was to evaluate the pre...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1007/s12012-013-9238-7

    authors: Li C,He J,Gao Y,Xing Y,Hou J,Tian J

    更新日期:2014-06-01 00:00:00

  • Intracellular levels of Na(+) and TTX-sensitive Na(+) channel current in diabetic rat ventricular cardiomyocytes.

    abstract::Intracellular Na(+) ([Na(+)](i)) is an important modulator of excitation-contraction coupling via regulating Ca(2+) efflux/influx, and no investigation has been so far performed in diabetic rat heart. Here, we examined whether any change of [Na(+)](i) in paced cardiomyocytes could contribute to functional alterations ...

    journal_title:Cardiovascular toxicology

    pub_type: 杂志文章

    doi:10.1007/s12012-012-9192-9

    authors: Bilginoglu A,Kandilci HB,Turan B

    更新日期:2013-06-01 00:00:00