Developmental toxicity and angiogenic defects of etoxazole exposed zebrafish (Danio rerio) larvae

Park, Hahyun; Lee, Jin Young; Song, Gwonhwa; Lim, Whasun

doi:10.1016/j.aquatox.2019.105324

Cited by 27 publications

(19 citation statements)

References 29 publications

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“…2013 ). Interestingly, these phenotypes similar to those observed in etoxazole treated zebrafish larva ( Park et al. 2019 ) were also described in zebrafish valveless Jekyll mutant ( Walsh and Stainier 2001 ) with the loss of function of UDP-glucose dehydrogenase (UGDH).…”

Section: Discussionsupporting

confidence: 57%

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Inhibition of hyaluronan secretion by novel coumarin compounds and chitin synthesis inhibitors

et al. 2021

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Elevated plasma levels of hyaluronic acid (HA) is a disease marker in liver pathology and other inflammatory disorders. Inhibition of HA synthesis with coumarin 4-methylumbelliferone (4MU) has a beneficial effect in animal models of fibrosis, inflammation, cancer and metabolic syndrome. 4MU is an active compound of approved choleretic drug hymecromone with low bioavailability and a broad spectrum of action. New, more specific, and efficient inhibitors of hyaluronan synthases (HAS) are required. We have tested several newly synthesized coumarin compounds and commercial chitin synthesis inhibitors to inhibit HA production in cell culture assay. Coumarin derivative compound VII (10′-methyl-6′-phenyl-3’H-spiro[piperidine-4,2′-pyrano[3,2-g]chromene]-4′,8′-dione) demonstrated inhibition of HA secretion by NIH3T3 cells with the half-maximal inhibitory concentration (IC50) = 1.69 ± 0.75 μΜ superior to 4MU (IC50 = 8.68 ± 1.6 μΜ). Inhibitors of chitin synthesis, etoxazole, buprofezin, triflumuron, reduced HA deposition with IC50 of 4.21 ± 3.82 μΜ, 1.24 ± 0.87 μΜ, and 1.48 ± 1.44 μΜ, respectively. Etoxazole reduced HA production and prevented collagen fibre formation in the CCl4 liver fibrosis model in mice similar to 4MU. Bioinformatics analysis revealed homology between chitin synthases and HAS enzymes, particularly in the pore-forming domain, containing the proposed site for etoxazole binding.

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Section: Discussionsupporting

confidence: 57%

“…Recently it was shown that etoxazole inhibits cardiovascular development in zebrafish embryos ( Park et al. 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of hyaluronan secretion by novel coumarin compounds and chitin synthesis inhibitors

et al. 2021

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“…For angiogenesis validation, we maintained zebrafish as described previously [ 13 ], and treated them with methiothepin at the indicated concentrations. The effects of methiothepin on blood vessel formation were evaluated by Fli-tagged GFP fluorescence signals.…”

Section: Methodsmentioning

confidence: 99%

Methiothepin Suppresses Human Ovarian Cancer Cell Growth by Repressing Mitochondrion-Mediated Metabolism and Inhibiting Angiogenesis In Vivo

et al. 2020

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Ovarian cancer is the fifth leading cause of cancer-related deaths in women. Despite treatment, most patients experience relapse and the 5-year survival rate of ovarian cancer is less than 50%. Serotonin has cell growth-promoting functions in a variety of carcinomas, but the effect of serotonin receptor antagonists on ovarian cancer cells is unknown. In this study, it was confirmed that methiothepin, a serotonin receptor antagonist, suppresses the viability of, and induces apoptosis in, ovarian cancer cells. Methiothepin also induces mitochondrial dysfunction, represented by depolarization of the mitochondrial membrane and increased mitochondrion-specific Ca2+ levels, and causes metabolic disruption in cancer cells such as decreased ATP production and oxidative phosphorylation. Methiothepin also interferes with vascular development in transgenic zebrafish embryos. Combination treatment with methiothepin improves the anti-cancer effect of paclitaxel, a standard chemotherapeutic agent. In conclusion, this study revealed that methiothepin is a potential novel therapeutic agent for ovarian cancer treatment.

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“…Like human embryos, zebrafish embryos possess a protruding yolk sac, but in zebrafish, it serves as a nutritional reservoir for the embryo [ 36 , 43 ]. Yolk sac edema is a common pathology in toxicity tests of zebrafish [ 32 , 150 ], and it is a sign of reduced nutrient adsorption by the embryo [ 43 ]. It may be affected by overhydration of osmoregulation and toxin accumulation in the yolk sac [ 150 ].…”

Section: Defects In Zebrafish Organs Found In Developmental Toxicimentioning

confidence: 99%

“…Yolk sac edema is a common pathology in toxicity tests of zebrafish [ 32 , 150 ], and it is a sign of reduced nutrient adsorption by the embryo [ 43 ]. It may be affected by overhydration of osmoregulation and toxin accumulation in the yolk sac [ 150 ]. Malformation in other organ systems that help allocate nutrients may be the trigger for this deficiency.…”

Section: Defects In Zebrafish Organs Found In Developmental Toxicimentioning

confidence: 99%

Zebrafish as a Successful Animal Model for Screening Toxicity of Medicinal Plants

Chahardehi

Arsad

Lim

2020

Plants

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The zebrafish (Danio rerio) is used as an embryonic and larval model to perform in vitro experiments and developmental toxicity studies. Zebrafish may be used to determine the toxicity of samples in early screening assays, often in a high-throughput manner. The zebrafish embryotoxicity model is at the leading edge of toxicology research due to the short time required for analyses, transparency of embryos, short life cycle, high fertility, and genetic data similarity. Zebrafish toxicity studies range from assessing the toxicity of bioactive compounds or crude extracts from plants to determining the optimal process. Most of the studied extracts were polar, such as ethanol, methanol, and aqueous solutions, which were used to detect the toxicity and bioactivity. This review examines the latest research using zebrafish as a study model and highlights its power as a tool for detecting toxicity of medicinal plants and its effectiveness at enhancing the understanding of new drug generation. The goal of this review was to develop a link to ethnopharmacological zebrafish studies that can be used by other researchers to conduct future research.

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Developmental toxicity and angiogenic defects of etoxazole exposed zebrafish (Danio rerio) larvae

Cited by 27 publications

References 29 publications

Inhibition of hyaluronan secretion by novel coumarin compounds and chitin synthesis inhibitors

Inhibition of hyaluronan secretion by novel coumarin compounds and chitin synthesis inhibitors

Methiothepin Suppresses Human Ovarian Cancer Cell Growth by Repressing Mitochondrion-Mediated Metabolism and Inhibiting Angiogenesis In Vivo

Zebrafish as a Successful Animal Model for Screening Toxicity of Medicinal Plants

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