Proteomic insights into chronic anthracycline cardiotoxicity

Štěrba, Martin; Popelová, Olga; Lenčo, Juraj; Fučíková, Alena; Brčáková, Eva; Mazurová, Y; Jirkovský, Eduard; Šimůnek, Tomáš; Adamcová, Michaela; Mičuda, Stanislav; Stulı́k, Jiřı́; Geršl, Vladimír

doi:10.1016/j.yjmcc.2011.01.018

Cited by 58 publications

(35 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As a consequence, the ATP generation in heart mitochondria decreased (Rossato et al 2014). These results are in agreement with those obtained in rats treated with daunorubicin, which demonstrated an increase in complex IV and V protein expression and a decrease in complex I activity and expression (Stěrba et al 2011). Anthracyclines can also form complexes with iron, producing ROS via a redox cycle (Link et al 1996).…”

Section: Ros Generation Iron Accumulation and Mitochondrial Dysfuncsupporting

confidence: 91%

Pathways of cardiac toxicity: comparison between chemotherapeutic drugs doxorubicin and mitoxantrone

et al. 2016

View full text Add to dashboard Cite

Anthracyclines, e.g., doxorubicin (DOX), and anthracenediones, e.g., mitoxantrone (MTX), are drugs used in the chemotherapy of several cancer types, including solid and non-solid malignancies such as breast cancer, leukemia, lymphomas, and sarcomas. Although they are effective in tumor therapy, treatment with these two drugs may lead to side effects such as arrhythmia and heart failure. At the same clinically equivalent dose, MTX causes slightly reduced cardiotoxicity compared with DOX. These drugs interact with iron to generate reactive oxygen species (ROS), target topoisomerase 2 (Top2), and impair mitochondria. These are some of the mechanisms through which these drugs induce late cardiomyopathy. In this review, we compare the cardiotoxicities of these two chemotherapeutic drugs, DOX and MTX. As described here, even though they share similarities in their modes of toxicant action, DOX and MTX seem to differ in a key aspect. DOX is a more redox-interfering drug, while MTX induces energy imbalance. In addition, DOX toxicity can be explained by underlying mechanisms that include targeting of Top2 beta, mitochondrial impairment, and increases in ROS generation. These modes of action have not yet been demonstrated for MTX, and this knowledge gap needs to be filled.

show abstract

Section: Ros Generation Iron Accumulation and Mitochondrial Dysfuncsupporting

confidence: 91%

Pathways of cardiac toxicity: comparison between chemotherapeutic drugs doxorubicin and mitoxantrone

et al. 2016

View full text Add to dashboard Cite

show abstract

“…31) ROS-caused mitochondrial dysfunction always leads to a tremendous decrease in ATP biosynthesis and a release of CytC, 15,32) which in turn further aggravates itself. This forms a catastrophic cycle of mitochondrial functional declination, leading to ATP depletion and ROS excess, which could induce Bax translocation from cytosol to mitochondria, resulting in the activation of MAP.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV Inhibits Doxorubicin-Induced Cardiomyocyte Apoptosis Mediated by Mitochondrial Apoptotic Pathway <i>via</i> Activating the PI3K/Akt Pathway

Jia

Zuo

et al. 2014

Chem. Pharm. Bull.

View full text Add to dashboard Cite

“…The study was performed by using the previously well established animal model of chronic ANT cardiotoxicity (Š imů nek et al, 2004;Popelová et al, 2009;Š těrba et al, 2011). Adult male Chinchilla rabbits (ϳ4 months old; ϳ3.5 kg; n ϭ 46; Velaz, Koleč u Kladna, Czech Republic) were housed under a 12-h light cycle with constant temperature and humidity and free access to tap water and a standard laboratory pellet diet.…”

Section: Methodsmentioning

confidence: 99%

Chronic Anthracycline Cardiotoxicity: Molecular and Functional Analysis with Focus on Nuclear Factor Erythroid 2-Related Factor 2 and Mitochondrial Biogenesis Pathways

Jirkovský

Popelová

Kriváková-Stanková

et al. 2012

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

Anthracycline anticancer drugs (e.g., doxorubicin or daunorubicin) can induce chronic cardiotoxicity and heart failure (HF), both of which are believed to be based on oxidative injury and mitochondrial damage. In this study, molecular and functional changes induced by chronic anthracycline treatment with progression into HF in post-treatment follow-up were analyzed with special emphasis on nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor-␥ coactivator-1␣ (PGC1␣) pathways. Chronic cardiotoxicity was induced in rabbits with daunorubicin (3 mg/kg, weekly for 10 weeks), and the animals were followed for another 10 weeks. Echocardiography revealed a significant drop in left ventricular (LV) systolic function during the treatment with marked progression to LV dilation and congestive HF in the follow-up. Although daunorubicin-induced LV lipoperoxidation was found, it was only loosely associated with cardiac performance. Furthermore, although LV oxidized glutathione content was increased, the oxidized-to-reduced glutathione ratio itself remained unchanged. Neither Nrf2, the master regulator of antioxidant response, nor the majority of its target genes showed up-regulation in the study. However, down-regulation of manganese superoxide dismutase and NAD(P)H dehydrogenase [quinone] 1 were observed together with heme oxygenase 1 up-regulation. Although marked perturbations in mitochondrial functions were found, no induction of PGC1␣-controlled mitochondrial biogenesis pathway was revealed. Instead, especially in the post-treatment period, an impaired regulation of this pathway was observed along with down-regulation of the expression of mitochondrial genes. These results imply that global oxidative stress need not be a factor responsible for the development of anthracycline-induced HF, whereas suppression of mitochondrial biogenesis might be involved.

show abstract

Proteomic insights into chronic anthracycline cardiotoxicity

Cited by 58 publications

References 49 publications

Pathways of cardiac toxicity: comparison between chemotherapeutic drugs doxorubicin and mitoxantrone

Pathways of cardiac toxicity: comparison between chemotherapeutic drugs doxorubicin and mitoxantrone

Astragaloside IV Inhibits Doxorubicin-Induced Cardiomyocyte Apoptosis Mediated by Mitochondrial Apoptotic Pathway <i>via</i> Activating the PI3K/Akt Pathway

Chronic Anthracycline Cardiotoxicity: Molecular and Functional Analysis with Focus on Nuclear Factor Erythroid 2-Related Factor 2 and Mitochondrial Biogenesis Pathways

Contact Info

Product

Resources

About