Zebrafish as a Vertebrate Model System to Evaluate Effects of Environmental Toxicants on Cardiac Development and Function

Sarmah, Swapnalee

doi:10.3390/ijms17122123

Cited by 121 publications

(73 citation statements)

References 89 publications

(129 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given these encouraging data, we investigated additional toxicity parameters on zebra sh embryos by monitoring the effects of increasing concentrations of JVG045 and corresponding percentages of DMSO on heartbeat. The normal zebra sh embryonic heartbeat rate is 140-180 beats per minute (bpm); this parameter is an established criterion for the evaluation of substance toxicity (39). Our analyses showed that heartbeat rates did not differ from data reported in the literature across all concentrations (DMSO average 142.0 bpm ± 11.17 SD; JVG045 average 138.4 bpm ± 12.95).…”

Section: Resultsmentioning

confidence: 53%

Rhenium N-heterocyclic Carbene Complexes Block Growth of Aggressive Cancers by Inhibiting FGFR- and SRC-Mediated Signalling

Domenichini

Casari

Simpson

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Platinum-based anticancer drugs have been at the frontline of cancer therapy for the last 40 years, and are used in more than half of all treatments for different cancer types. However, they are not universally effective, and patients often suffer severe side effects because of their lack of cellular selectivity. There is therefore a compelling need to investigate the anticancer activity of alternative metal complexes. Here we describe the potential anticancer activity of rhenium-based complexes with preclinical efficacy in different types of solid malignancies.Methods: Kinase profile assay of rhenium complexes. Toxicology studies using zebrafish. Analysis of the growth of pancreatic cancer cell line-derived xenografts generated in zebrafish and in mice upon exposure to rhenium compounds.Results: We describe rhenium complexes which block cancer proliferation in vitro by inhibiting the signalling cascade induced by FGFR and Src. Initially, we tested the toxicity of rhenium complexes in vivo using a zebrafish model and identified one compound that displays anticancer activity with low toxicity even in the high micromolar range. Notably, the rhenium complex has anticancer activity in very aggressive cancers such as pancreatic ductal adenocarcinoma and neuroblastoma. We demonstrate the potential efficacy of this complex via a significant reduction in cancer growth in mouse xenografts.Conclusions: Our findings provide a basis for the development of rhenium-based chemotherapy agents with enhanced selectivity and limited side effects compared to standard platinum-based drugs.

show abstract

Section: Resultsmentioning

confidence: 53%

Rhenium N-heterocyclic Carbene Complexes Block Growth of Aggressive Cancers by Inhibiting FGFR- and SRC-Mediated Signalling

Domenichini

Casari

Simpson

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Cardiotoxicity was also evaluated in vivo using a wild-type zebrafish (AB) strain and a cmlc2 EGFP transgenic zebrafish The zebrafish provides an extremely useful in vivo model in which to study the effects of drugs or toxic substances on vertebrate development, and particularly on cardiac development [16,17]. A previous report found that the overall predictive success rate of zebrafish for cardiotoxicity was 100% [18].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Cardiotoxicity of Evodiamine <em>In Vitro</em> and<em> In Vivo</em>

Yang

et al. 2017

Preprint

View full text Add to dashboard Cite

Evodiamine is a bioactive alkaloid that is specified as a biomarker for the quality assessment of Evodia rutaecarpa and for traditional Chinese medicines containing this plant. We previously reported that quantitative structure-activity modeling indicated that evodiamine may cause cardiotoxicity. However, previous investigations have indicated that evodiamine has beneficial effects in patients with cardiovascular diseases and there are no previous in vitro or in vivo reports of evodiamine-induced cardiotoxicity. The present study investigated the effects of evodiamine on primary cultured neonatal rat cardiomyocytes in vitro, and on zebrafish in vivo. Cell viability was reduced in vitro, where evodiamine had a 24-h 50% inhibitory concentration of 28.44 µg/mL. Cells exposed to evodiamine also showed increased lactate dehydrogenase release and maleic dialdehyde levels, and reduced superoxide dismutase activity. In vivo, evodiamine had a 10% lethal concentration of 354 ng/mL and induced cardiac malfunction, as evidenced by changes in heart rate and circulation, and pericardial malformations. This study indicated that evodiamine Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted:

show abstract

“…Thus, it is unsuitable to model pseudokinases in a zebrafish model. (6) The drug exposure method for zebrafish is mainly bathing, and caution should be taken with insoluble drugs and drug metabolism . Therapeutic antibodies are large therapeutic molecules that differ from small molecule agents in absorption, distribution, and elimination properties between the two classes of drugs in a systematic manner .…”

Section: Research Gaps Challenges Perspectives and Opportunities Tmentioning

confidence: 99%

“…(6) The drug exposure method for zebrafish is mainly bathing, and caution should be taken with insoluble drugs and drug metabolism. 465,466 Therapeutic antibodies are large therapeutic molecules that differ from small molecule agents in absorption, distribution, and elimination properties between the two classes of drugs in a systematic manner. 467 (1) Absorption: the absorption of small and large molecules differs with respect to their common extravascular routes of delivery (oral for small molecule agents versus injection for antibodies).…”

Section: Zebrafish Modelmentioning

confidence: 99%

Breakthroughs in modern cancer therapy and elusive cardiotoxicity: Critical research‐practice gaps, challenges, and insights

Zheng

Kros

2017

Medicinal Research Reviews

View full text Add to dashboard Cite

To date, five cancer treatment modalities have been defined. The three traditional modalities of cancer treatment are surgery, radiotherapy, and conventional chemotherapy, and the two modern modalities include molecularly targeted therapy (the fourth modality) and immunotherapy (the fifth modality). The cardiotoxicity associated with conventional chemotherapy and radiotherapy is well known. Similar adverse cardiac events are resurging with the fourth modality. Aside from the conventional and newer targeted agents, even the most newly developed, immune‐based therapeutic modalities of anticancer treatment (the fifth modality), e.g., immune checkpoint inhibitors and chimeric antigen receptor (CAR) T‐cell therapy, have unfortunately led to potentially lethal cardiotoxicity in patients. Cardiac complications represent unresolved and potentially life‐threatening conditions in cancer survivors, while effective clinical management remains quite challenging. As a consequence, morbidity and mortality related to cardiac complications now threaten to offset some favorable benefits of modern cancer treatments in cancer‐related survival, regardless of the oncologic prognosis. This review focuses on identifying critical research‐practice gaps, addressing real‐world challenges and pinpointing real‐time insights in general terms under the context of clinical cardiotoxicity induced by the fourth and fifth modalities of cancer treatment. The information ranges from basic science to clinical management in the field of cardio‐oncology and crosses the interface between oncology and onco‐pharmacology. The complexity of the ongoing clinical problem is addressed at different levels. A better understanding of these research‐practice gaps may advance research initiatives on the development of mechanism‐based diagnoses and treatments for the effective clinical management of cardiotoxicity.

show abstract

Zebrafish as a Vertebrate Model System to Evaluate Effects of Environmental Toxicants on Cardiac Development and Function

Cited by 121 publications

References 89 publications

Rhenium N-heterocyclic Carbene Complexes Block Growth of Aggressive Cancers by Inhibiting FGFR- and SRC-Mediated Signalling

Rhenium N-heterocyclic Carbene Complexes Block Growth of Aggressive Cancers by Inhibiting FGFR- and SRC-Mediated Signalling

Evaluation of the Cardiotoxicity of Evodiamine <em>In Vitro</em> and<em> In Vivo</em>

Breakthroughs in modern cancer therapy and elusive cardiotoxicity: Critical research‐practice gaps, challenges, and insights

Contact Info

Product

Resources

About