Macrolides induce severe cardiotoxicity and developmental toxicity in zebrafish embryos

Yan, Zhaoyang; Huang, Xiaoyong; Xie, Yun; Song, Meirong; Zhu, Kui; Ding, Shuangyang

doi:10.1016/j.scitotenv.2018.07.432

Cited by 68 publications

(34 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In some cases, "modified structure of chorda" [69], "body shape" [69], "notochord anomalies", "tail anomalies", and "kinks (wavy, curled, bend)" were employed to describe spinal cord malformations without further distinction [83]. No further publications could be found, directly discussing the different curvatures observed in zebrafish embryos, although-according to the present study-spinal curvature is a group of endpoints quite frequently observed (Table 2); with the literature providing the further examples [55,[84][85][86][87][88][89][90].…”

Section: Sublethal Morphological Alterations In Zebrafish Embryos Witmentioning

confidence: 85%

Adverse effects in the fish embryo acute toxicity (FET) test: a catalogue of unspecific morphological changes versus more specific effects in zebrafish (Danio rerio) embryos

et al. 2020

View full text Add to dashboard Cite

Background The Fish Embryo Acute Toxicity (FET) test with the zebrafish (Danio rerio) embryo, the OECD test guideline (TG) 236, has been designed as an alternative for acute fish toxicity testing such as the OECD Acute Fish Toxicity Test (TG 203). To provide equivalent sensitivity to the acute fish test, the original FET test was designed to use only four morphological core endpoints: coagulation of the embryo, lack of somite formation, lack of heart beat, and non-detachment of the tail. These endpoints were selected due to (1) their association with mortality, directly or indirectly, (2) improve the practicality for screening by well-trained technical staff, and (3) the endpoints being relatively simple morphological alterations. Results With the growing need to understand the developmental toxicity of compounds found in the environment, the FET protocol has repeatedly been extended to a multitude of additional morphological endpoints that also allow the monitoring of teratogenicity. As the extensive use of the FET test has generated a multitude of observations in the scientific literature, a harmonisation of the terminology used for the description of the morphological effects seen after chemical exposure has become necessary. Conclusion For this end, the present communication provides an overview of both common and selected more specific morphological effects seen in zebrafish embryos after exposure to a wide variety of chemical substances together with suggestions for a harmonised nomenclature.

show abstract

Section: Sublethal Morphological Alterations In Zebrafish Embryos Witmentioning

confidence: 85%

Adverse effects in the fish embryo acute toxicity (FET) test: a catalogue of unspecific morphological changes versus more specific effects in zebrafish (Danio rerio) embryos

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Exposure for 4 days to 0.2–0.6 mg/L of triclosan decreased body length, head, and eye size in Danio rerio embryos and activated apoptosis in central nervous system which resulted in decreased synaptic density and decrease in axon length [ 118 ]. Yan et al [ 119 ] reported that exposure of Danio rerio embryos to macrolide antibiotics (azithromycin, clarithromycin, tilmicosin, and tylosin) resulted in cardiotoxicity: increased heart rate and pericardial edema. It was accompanied by spine curvatures, increased apoptosis rate, and oxidative stress.…”

Section: Toxic Effects Of Antibacterials On Fish Organismsmentioning

confidence: 99%

Antibacterials in Aquatic Environment and Their Toxicity to Fish

2020

View full text Add to dashboard Cite

Antibacterial agents are commonly present in aquatic environment at low concentrations. Terrestrial animal farms, human medicine and aquaculture are main sources of water contamination with antibacterials. Antibiotics were proved to be directly toxic to fish causing oxidative stress, general stress response, histopathological lesions, hematological, metabolic, and reproductive disorders, as well as immunosuppressive and genotoxic effects. Environmentally realistic low concentrations of antibiotics also disturb aquatic bacterial communities causing alterations in fish symbiotic microbiota and induce emergence of antibiotic-resistant pathogenic bacteria by exerting selective pressure on spread of antibiotic-resistance genes.

show abstract

“…Zebrafish embryos are small and relatively transparent, and multiple organs can be observed directly under the microscope. The heart is an important organ in the development of zebrafish embryos [21], and the gastrointestinal tract plays a major role in mucosal homeostasis, barrier function and immunity [22]. However, abnormal heart rate, pericardial edema, and gastrointestinal motility lead to abnormality of embryonic development or even death [23,24].…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, zebrafish embryos were transferred into AO solution (4 mg/L) in darkness for 1.5 h at room temperature [21]. Then, the embryos were gently rinsed three times with phosphate buffered saline (PBS) (Gibco, Thermo Fisher, Waltham, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

Toxicity Reduction of Euphorbia kansui Stir-Fried with Vinegar Based on Conversion of 3-O-(2′E,4′Z-Decadi-enoyl)-20-O-acetylingenol

Zhang

Zhou

et al. 2019

Molecules

View full text Add to dashboard Cite

The dried roots of Euphorbia kansui S.L.Liou ex S.B.Ho have long been used to treat edema in China. However, the severe toxicity caused by Euphorbia kansui (EK) has seriously restricted its clinical application. Although EK was processed with vinegar to reduce its toxicity, the detailed mechanisms of attenuation in toxicity of EK stir-fried with vinegar (VEK) have not been well delineated. Diterpenoids are the main toxic ingredients of EK, and changes in these after processing may be the underlying mechanism of toxicity attenuation of VEK. 3-O-(2′E,4′Z-decadienoyl)-20-O-acetylingenol (3-O-EZ) is one of the diterpenoids derived from EK, and the content of 3-O-EZ was significantly reduced after processing. This study aims to explore the underlying mechanisms of toxicity reduction of VEK based on the change of 3-O-EZ after processing with vinegar. Based on the chemical structure of 3-O-EZ and the method of processing with vinegar, simulation experiments were carried out to confirm the presence of the product both in EK and VEK and to enrich the product. Then, the difference of peak area of 3-O-EZ and its hydrolysate in EK and VEK were detected by ultra-high-performance liquid chromatography (UPLC). Furthermore, the toxicity effect of 3-O-EZ and its hydrolysate, as well as the underlying mechanism, on zebrafish embryos were investigated. The findings showed that the diterpenoids (3-O-EZ) in EK can convert into less toxic ingenol in VEK after processing with vinegar; meanwhile, the content of ingenol in VEK was higher than that of EK. More interestingly, the ingenol exhibited less toxicity (acute toxicity, developmental toxicity and organic toxicity) than that of 3-O-EZ, and 3-O-EZ could increase malondialdehyde (MDA) content and reduce glutathione (GSH) content; cause embryo oxidative damage by inhibition of the succinate dehydrogenase (SDH) and superoxide dismutase (SOD) activity; and induce inflammation and apoptosis by elevation of IL-2 and IL-8 contents and activation of the caspase-3 and caspase-9 activity. Thus, this study contributes to our understanding of the mechanism of attenuation in toxicity of VEK, and provides the possibility of safe and rational use of EK in clinics.

show abstract

Macrolides induce severe cardiotoxicity and developmental toxicity in zebrafish embryos

Cited by 68 publications

References 68 publications

Adverse effects in the fish embryo acute toxicity (FET) test: a catalogue of unspecific morphological changes versus more specific effects in zebrafish (Danio rerio) embryos

Adverse effects in the fish embryo acute toxicity (FET) test: a catalogue of unspecific morphological changes versus more specific effects in zebrafish (Danio rerio) embryos

Antibacterials in Aquatic Environment and Their Toxicity to Fish

Toxicity Reduction of Euphorbia kansui Stir-Fried with Vinegar Based on Conversion of 3-O-(2′E,4′Z-Decadi-enoyl)-20-O-acetylingenol

Contact Info

Product

Resources

About