AUTHOR=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 TITLE=Integration of Transcriptomic and Metabolomic Data to Compare the Hepatotoxicity of Neonatal and Adult Mice Exposed to Aristolochic Acid I JOURNAL=Frontiers in Genetics VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.840961 DOI=10.3389/fgene.2022.840961 ISSN=1664-8021 ABSTRACT=

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.