Hepatic RNA adduction derived from metabolic activation of retrorsine in vitro and in vivo

Weiwei Li, Ting Cheng, Tingting Jiang, Mengyue Zhou, Bowen Gong, Guode Zhao, Jing Li, Rong Tan, Xiaojing Yang, Kandarp Joshi, Ying Peng, Maosheng Cheng, Ting Liu, Dan Ohtan Wang, Jiang Zheng

Research output: Contribution to journalArticlepeer-review


Pyrrolizidine alkaloids (PAs) are among the most significant hepatotoxins widely distributed in plant species. Incidence of liver injuries caused by PAs has been reported worldwide, and the reactive metabolites of PAs are known to play a critical role in causing the hepatotoxicity. To better understand the toxicity-induction mechanisms, we explored the interactions of PA metabolites with cellular RNA molecules, and examined their effects on the biochemical and metabolic properties of hepatic RNAs. After exposure to retrorsine, adduction on adenosine and guanosine were detected in mouse liver microsomal incubations, cultured mouse primary hepatocytes, and mouse liver tissues. NMR analysis showed that the exocyclic amino group participated in the adduction. We found drastically altered properties and metabolism of the adducted RNA such as reverse-transcriptability, translatability, and RNase-susceptibility. In addition, endogenous modification of N6-methyladenosine (m6A) was remarkably reduced.

Original languageEnglish (US)
Article number110047
JournalChemico-Biological Interactions
StatePublished - Sep 25 2022


  • Epigenetic toxicity
  • N-methyladenosine (m6A)
  • Pyrrolizidine alkaloids
  • Retrorsine
  • RNA adduction

ASJC Scopus subject areas

  • Toxicology


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