Cardiotoxicity evaluation of anthracyclines in zebrafish (<i>Danio rerio</i>)

Han, Ying; Zhang, Jing-pu; Qian, Jianqin; Hu, Chang‐Qin

doi:10.1002/jat.3007

Cited by 66 publications

(34 citation statements)

References 49 publications

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“…The correlation between cytotoxicity in vitro, accumulation of the tested anthracyclines in the nuclei of cardiomyoblasts, and their cardiotoxicity in vivo observed in our previous work [ 4 ] leads to the hypothesis that the cytotoxic potencies and the accumulation of anthracyclines in the nuclei of cultured cardiomyoblasts may be good and simple predictors of cardiotoxicity. This is an attractive possibility, as reliable methods that can be used for early prediction of anthracycline cardiotoxicity are needed [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Subcellular localization of anthracyclines in cultured rat cardiomyoblasts as possible predictors of cardiotoxicity

et al. 2015

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SummaryIn this study, we compared the cellular uptake, intracellular localization and cytotoxicity of two groups of anthracycline derivatives in cultured H9c2(2-1) rat cardiomyoblasts. The first group consisted of doxorubicin (DOX) and two of its derivatives containing a formamidino group (–N = CH–N<) at the C-3′ position with a morpholine (DOXM) or a hexamethyleneimine (DOXH) ring. The second group consisted of daunorubicin (DRB) and its derivatives containing a morpholine (DRBM) or a hexamethyleneimine (DRBH) ring. DOXH and DRBH were taken up by cardiomyoblasts more efficiently than estimated for other tested anthracyclines. The cellular uptakes of DOXM and DRBM were reduced compared to those of the parent compounds. Applied structural modifications of DOX and DRB influenced the subcellular localization of the tested derivatives. DOX and DOXH were localized primarily in nuclei, whereas the other anthracyclines were found in the nuclei and cytoplasm. The percentages of the compounds that accumulated in the nuclei were 80.2 and 54.2 % for DOX and DOXH, respectively. The lowest nuclear accumulation values were observed for DRBM (19.9 %), DRBH (21.9 %) and DOXM (23.7 %). The ability of anthracyclines to accumulate in the nuclei correlated with their DNA binding constants (r = 0.858, P = 0.029). A correlation was found between the accumulation of the tested anthracyclines in the nuclei of cardiomyoblasts and their cardiotoxicity in vivo, which was observed in our previous study. We suggest that cytotoxicity and the anthracycline accumulation level in the nuclei of cultured cardiomyoblasts could be used for early prediction of their cardiotoxicity.

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Section: Discussionmentioning

confidence: 99%

Subcellular localization of anthracyclines in cultured rat cardiomyoblasts as possible predictors of cardiotoxicity

et al. 2015

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“…Zebrafish ( Danio rerio ) of the AB wild-type strain and TG (VEGFR2:GFP) type strain were maintained under a 14 h light/10 h dark cycle in an automatic circulating tank system and fed with artificial granular bait and fresh Artemia nauplii [ 21 ]. Adult mating pairs were placed in a breeding tank in the evening, and fertilized eggs were collected in the next morning (9 h).…”

Section: Methodsmentioning

confidence: 99%

Alkaloids with Cardiovascular Effects from the Marine-Derived Fungus Penicillium expansum Y32

Fan

Chao

et al. 2015

Marine Drugs

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Three new alkaloids (1, 4 and 8), together with nine known analogues (2, 3, 5–7, and 9–12), were isolated from the marine-derived fungus Penicillium expansum Y32. Their structures including the absolute configurations were elucidated by spectroscopic and Mosher’s and Marfey’s methods, along with quantum electronic circular dichroism (ECD) calculations. Each of the compounds was evaluated for cardiovascular effects in a live zebrafish model. All of the compounds showed a significant mitigative effect on bradycardia caused by astemizole (ASM) in the heart rate experiments. Compounds 4–6 and 8–12 exhibited potent vasculogenetic activity in vasculogenesis experiments. This is the first study to report that these types of compounds show cardiovascular effects in zebrafish. The results suggest that these compounds could be promising candidates for cardiovascular disease lead compounds.

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“…One of the widely used anticancer drugs belongs to the Anthracyclines (ANTs) class; Daunorubicin, Pirarubicin, Doxorubicin (DOX), Epirubicin, and DOX-liposome. Han et al exposed zebrafish embryos to a variety of ANTs that resulted in incomplete looping of the heart tube, pericardial edema and bradycardia in dose-dependent manner [ 25 ]. The greatest defect was produced by DOX, whereas Daunorubicin produced the minimum toxicity.…”

Section: Zebrafish Cardiotoxicity Studiesmentioning

confidence: 99%

Using Zebrafish for Investigating the Molecular Mechanisms of Drug-Induced Cardiotoxicity

Zakaria

Benslimane

Nasrallah

et al. 2018

BioMed Research International

104

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Over the last decade, the zebrafish (Danio rerio) has emerged as a model organism for cardiovascular research. Zebrafish have several advantages over mammalian models. For instance, the experimental cost of using zebrafish is comparatively low; the embryos are transparent, develop externally, and have high fecundity making them suitable for large-scale genetic screening. More recently, zebrafish embryos have been used for the screening of a variety of toxic agents, particularly for cardiotoxicity testing. Zebrafish has been shown to exhibit physiological responses that are similar to mammals after exposure to medicinal drugs including xenobiotics, hormones, cancer drugs, and also environmental pollutants, including pesticides and heavy metals. In this review, we provided a summary for recent studies that have used zebrafish to investigate the molecular mechanisms of drug-induced cardiotoxicity. More specifically, we focused on the techniques that were exploited by us and others for cardiovascular toxicity assessment and described several microscopic imaging and analysis protocols that are being used for the estimation of a variety of cardiac hemodynamic parameters.

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Cardiotoxicity evaluation of anthracyclines in zebrafish (Danio rerio)

Cited by 66 publications

References 49 publications

Subcellular localization of anthracyclines in cultured rat cardiomyoblasts as possible predictors of cardiotoxicity

Subcellular localization of anthracyclines in cultured rat cardiomyoblasts as possible predictors of cardiotoxicity

Alkaloids with Cardiovascular Effects from the Marine-Derived Fungus Penicillium expansum Y32

Using Zebrafish for Investigating the Molecular Mechanisms of Drug-Induced Cardiotoxicity

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