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Toxic effects of flufenoxuron on development and vascular formation during zebrafish embryogenesis.
Aquat Toxicol 2019; 216:105307AT

Abstract

Flufenoxuron, a chitin synthesis inhibitor that is widely used in developed countries as an insecticide, is rarely degraded in the environment. In addition to that in insects, flufenoxuron-mediated non-targeted death in organisms such as lizards and bees has been reported. However, the toxic effects of this compound on vascular development during embryogenesis, as well as the underlying mechanism, have not yet been elucidated. In the present study, we assessed abnormal development and cardiovascular damage induced by flufenoxuron in zebrafish embryos. Exposed zebrafish had malformed eyes and pathological characteristics such as heart and yolk sac edema. In accordance with developmental inhibition, cell cycle regulatory genes were dysregulated in zebrafish embryos upon exposure to flufenoxuron. We also discovered that this agent can disrupt vascular formation by interfering with angiogenesis-associated genes including the genes encoding vascular endothelial growth factor Aa (vegfaa), vegfc, fms-related tyrosine kinase 1 (flt1), and flt4 in zebrafish embryos. These anti-angiogenic effects of flufenoxuron were further verified using a well-known angiogenesis model, namely human umbilical vein endothelial cells. In conclusion, our results suggest that flufenoxuron inhibits overall development and angiogenesis during embryogenesis.

Authors+Show Affiliations

Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea. Electronic address: ghsong@korea.ac.kr.Department of Food and Nutrition, Kookmin University, Seoul, 02707, Republic of Korea. Electronic address: wlim@kookmin.ac.kr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31557631

Citation

Park, Sunwoo, et al. "Toxic Effects of Flufenoxuron On Development and Vascular Formation During Zebrafish Embryogenesis." Aquatic Toxicology (Amsterdam, Netherlands), vol. 216, 2019, p. 105307.
Park S, Lee JY, Park H, et al. Toxic effects of flufenoxuron on development and vascular formation during zebrafish embryogenesis. Aquat Toxicol. 2019;216:105307.
Park, S., Lee, J. Y., Park, H., Song, G., & Lim, W. (2019). Toxic effects of flufenoxuron on development and vascular formation during zebrafish embryogenesis. Aquatic Toxicology (Amsterdam, Netherlands), 216, p. 105307. doi:10.1016/j.aquatox.2019.105307.
Park S, et al. Toxic Effects of Flufenoxuron On Development and Vascular Formation During Zebrafish Embryogenesis. Aquat Toxicol. 2019;216:105307. PubMed PMID: 31557631.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Toxic effects of flufenoxuron on development and vascular formation during zebrafish embryogenesis. AU - Park,Sunwoo, AU - Lee,Jin-Young, AU - Park,Hahyun, AU - Song,Gwonhwa, AU - Lim,Whasun, Y1 - 2019/09/18/ PY - 2019/07/23/received PY - 2019/09/17/revised PY - 2019/09/17/accepted PY - 2019/9/27/pubmed PY - 2019/12/21/medline PY - 2019/9/27/entrez KW - Angiogenesis KW - Development KW - Embryotoxicity KW - Flufenoxuron KW - Zebrafish SP - 105307 EP - 105307 JF - Aquatic toxicology (Amsterdam, Netherlands) JO - Aquat. Toxicol. VL - 216 N2 - Flufenoxuron, a chitin synthesis inhibitor that is widely used in developed countries as an insecticide, is rarely degraded in the environment. In addition to that in insects, flufenoxuron-mediated non-targeted death in organisms such as lizards and bees has been reported. However, the toxic effects of this compound on vascular development during embryogenesis, as well as the underlying mechanism, have not yet been elucidated. In the present study, we assessed abnormal development and cardiovascular damage induced by flufenoxuron in zebrafish embryos. Exposed zebrafish had malformed eyes and pathological characteristics such as heart and yolk sac edema. In accordance with developmental inhibition, cell cycle regulatory genes were dysregulated in zebrafish embryos upon exposure to flufenoxuron. We also discovered that this agent can disrupt vascular formation by interfering with angiogenesis-associated genes including the genes encoding vascular endothelial growth factor Aa (vegfaa), vegfc, fms-related tyrosine kinase 1 (flt1), and flt4 in zebrafish embryos. These anti-angiogenic effects of flufenoxuron were further verified using a well-known angiogenesis model, namely human umbilical vein endothelial cells. In conclusion, our results suggest that flufenoxuron inhibits overall development and angiogenesis during embryogenesis. SN - 1879-1514 UR - https://www.unboundmedicine.com/medline/citation/31557631/Toxic_effects_of_flufenoxuron_on_development_and_vascular_formation_during_zebrafish_embryogenesis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-445X(19)30584-3 DB - PRIME DP - Unbound Medicine ER -