4.7 Article

Transcriptome analysis of developing zebrafish (Danio rerio) embryo following exposure to Gaudichaudione H reveals teratogenicity and cardiovascular defects caused by abnormal iron metabolism

Journal

CHEMICO-BIOLOGICAL INTERACTIONS
Volume 361, Issue -, Pages -

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2022.109968

Keywords

Gaudichaudione H; Zebrafish; Caged xanthone; Iron metabolism; Cardiovascular toxicity; Teratogenicity

Funding

  1. PhD research startup foundation of Jiangxi University of Chinese Medicine [2021BSZR002]
  2. Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program, National Natural Science Founda-tion of China [21002085, 21362044, 21562046]
  3. Applied Basic Research Foundation of Yunnan Province [2016FB022]

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This study investigated the toxic effects of Gaudichaudione H (GH) using zebrafish embryos and larvae as an in vivo test model. The results showed that GH led to embryonic mortality, cardiotoxicity, cardiovascular defects, and other adverse effects in zebrafish embryos and larvae.
Gaudichaudione H (GH), a caged polyprenylated xanthone from Garcinia plants, showed anti-cancer and antiinflammatory effects in vitro. However, the in vivo toxicity of this compound has never been reported. The present study was aimed to address the toxic effects of Gaudichaudione H using zebrafish embryos and larvae as an in vivo test model. The zebrafish embryos were treated with GH having different concentrations (0, 0.28, 0.38 and 0.57 mu g/mL). The results revealed that GH induces significant embryonic mortality, decreased heartbeat, cardiotoxicity, cardiovascular defects, increased apoptosis and decreased hemoglobinization in zebrafish embryos and larvae. According to transcriptome analysis, 1841 genes were significantly differentially expressed (1185 down-regulated and 656 up-regulated) after GH treatment. The main functions of these genes were related to iron metabolism pathways. The toxicity of GH on zebrafish embryonic development and cardiovascular may due to large amounts of downregulated genes involved in metabolic pathways and DEGs related to 'Iron ion binding' and 'Heme binding' functions.

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