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Integration of Transcriptomic and Metabolomic Data to Compare the Hepatotoxicity of Neonatal and Adult Mice Exposed to Aristolochic Acid I

Aristolochic acid (AA) is a group of structurally related compounds what have been used to treat various diseases in recent decades. Aristolochic acid I (AAI), an important ingredient, has been associated with tumorigenesis. Recently, some studies indicated that AAI could induce liver injury in mice...

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Detalles Bibliográficos
Autores principales: Fang, Zhi-e, Wang, Chunyu, Niu, Ming, Liu, Tingting, Ren, Lutong, Li, Qiang, Li, Zhiyong, Wei, Ziying, Lin, Li, Mu, Wenqing, Gao, Yuan, Xiao, Xiaohe, Bai, Zhaofang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992794/
https://www.ncbi.nlm.nih.gov/pubmed/35401701
http://dx.doi.org/10.3389/fgene.2022.840961
Descripción
Sumario:Aristolochic acid (AA) is a group of structurally related compounds what have been used to treat various diseases in recent decades. Aristolochic acid I (AAI), an important ingredient, has been associated with tumorigenesis. Recently, some studies indicated that AAI could induce liver injury in mice of different age, but comprehensive mechanisms of AAI-induced differences in liver injury in various age groups have not yet been elucidated. This study aims to evaluate the causal relationship between AAI-induced liver injury and age based on neonatal mice and adult mice. A survival experiment indicated that all neonatal mice survived. Moreover, the adult mice in the high-dose AAI group all died, whereas half of the adult mice in the low-dose AAI group died. In observation experiments, AAI induced more severe liver injury in neonatal mice than adult mice under long-term than short-term exposure. Furthermore, integrated metabolomics and transcriptomics indicated that AAI disturbing steroid hormone biosynthesis, arachidonic acid metabolism, the drug metabolism-cytochrome P450 pathway and glycerophospholipid metabolism induced neonatal mice liver injury. The important role of age in AAI-induced liver injury was illustrated in our study. This study also lays a solid foundation for scientific supervision of AA safety.