The enhanced hepatotoxicity of isobavachalcone in depigmented zebrafish due to calcium signaling dysregulation and lipid metabolism disorder.

Autor: Zhang, Huiwen, Zhu, Chengyue, Zhao, Jingcheng, Zheng, Ruifang, Xing, Jianguo, Li, Zhijian, Zhang, Yun, Xu, Qian
Předmět:
Zdroj: Journal of Applied Toxicology; Jun2024, Vol. 44 Issue 6, p919-932, 14p
Abstrakt: Isobavachalcone (IBC) is a flavonoid component derived from Psoraleae Fructus that can increase skin pigmentation and treat vitiligo. However, IBC has been reported to be hepatotoxic. Current studies on IBC hepatotoxicity are mostly on normal organisms but lack studies on hepatotoxicity in patients. This study established the depigmented zebrafish model by using phenylthiourea (PTU) and investigated the difference in hepatotoxicity between normal and depigmented zebrafish caused by IBC and the underlying mechanism. Morphological, histological, and ultrastructural examination and RT–qPCR verification were used to evaluate the effects of IBC on the livers of zebrafish larvae. IBC significantly decreased liver volume, altered lipid metabolism, and induced pathological and ultrastructural changes in the livers of zebrafish with depigmentation compared with normal zebrafish. The RNA‐sequencing and RT–qPCR results showed that the difference in hepatotoxicity between normal and depigmented zebrafish caused by IBC was closely related to the calcium signaling pathway, lipid decomposition and metabolism, and oxidative stress. This work delved into the mechanism of the enhanced IBC‐induced hepatotoxicity in depigmented zebrafish and provided a new insight into the hepatotoxicity of IBC. Isobavachalcone (IBC) is a flavonoid component that can increase skin pigmentation. However, IBC has been reported to be hepatotoxic. Current studies of IBC hepatotoxicity have focused on normal organisms rather than patients. This study investigated the difference in hepatotoxicity between normal and depigmented zebrafish caused by IBC. The result showed that IBC had enhanced hepatotoxicity in depigmented zebrafish compared with normal zebrafish. IBC caused disturbances in the calcium signaling pathway, disrupted lipid metabolism, and induced oxidative stress in depigmented zebrafish. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index