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Investigation of the cardiovascular toxicity of oxidized cholesterols using the zebrafish as an animal model
Author(s) -
Kurogi Katsuhisa
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1199.8
Subject(s) - microinjection , zebrafish , toxicity , flow cytometry , cholesterol , cytotoxicity , animal model , yolk sac , medicine , endocrinology , chemistry , pharmacology , biology , immunology , biochemistry , embryo , microbiology and biotechnology , in vitro , gene
Zebrafish has been used as an animal model for the investigation of cardiovascular disorders. One of the major pathogenic factors for cardiovascular diseases, such as atherosclerosis, is oxidized cholesterols. The cytotoxicity of oxidized cholesterols for the vascular endothelial cells has been proposed to be an etiological factor for atherosclerosis. However, it is unclear which type(s) of oxidized cholesterol may exhibit more serious pathogenic effects. In the current study, the zebrafish was employed to verify the cardiovascular toxicities of oxidized cholesterols. Zebrafish larvae at 48 hours postfertilization (hpf) were exposed to cholesterol and 10 different oxidized cholesterols by the soaking method or by microinjection into yolk sac. At every 24 hours during exposure up to 7 dpf, heart beats, blood flow, and mortality were examined. To investigate further the effect on the cardiovascular system, o‐dianisidine staining was performed. 5,6α‐Epoxycholesterol and 5,6β‐epoxycholesterol, tested using both the soaking and the microinjection methods, showed the strongest cardiovascular toxicities, including lower heart beats, decreased blood flow, and higher mortality rate, among the oxidized cholesterols tested. Intriguingly, 22‐hydroxycholesterol exhibited a severe cardiovascular toxicity when tested using the soaking method, but not the microinjection method. Collectively, these results indicated that epoxycholesterols caused stronger cytotoxicity toward vascular endothelial cells than other oxidized cholesterols such as 7β‐hydroxycholesterol and 7‐ketocholesterol. Our results suggested that the zebrafish larva may serve as a convenient and useful model for investigating the pathogenicity and/or prevention of atherosclerosis caused by oxidized cholesterols.