1 research outputs found
Metabolomic and Genomic Evidence for Compromised Bile Acid Homeostasis by Senecionine, a Hepatotoxic Pyrrolizidine Alkaloid
Pyrrolizidine
alkaloids (PAs) are among the most hepatotoxic natural
products that produce irreversible injury to humans via the consumption
of herbal medicine and honey, and through tea preparation. Toxicity
and death caused by PA exposure have been reported worldwide. Metabolomics
and genomics provide scientific and systematic views of a living organism
and have become powerful techniques for toxicology research. In this
study, senecionine hepatotoxicity on rats was determined via a combination
of metabolomic and genomic analyses. From the global analysis generated
from two omics data, the compromised bile acid homeostasis in vivo
was innovatively demonstrated and confirmed. Serum profiling of bile
acids was altered with significantly elevated conjugated bile acids
after senecionine exposure, which was in accordance with toxicity.
Similarly, the hepatic mRNA levels of several key genes associated
with bile acid metabolism were significantly changed. This process
included cholesterol 7-α hydroxylase, bile acid CoA-amino acid <i>N</i>-acetyltransferase, sodium taurocholate cotransporting
polypeptide, organic anion-transporting polypeptides, and multidrug-resistance-associated
protein 3. In conclusion, a cross-omics study provides a comprehensive
analysis method for studying the toxicity caused by senecionine, which
is a hepatotoxic PA. Moreover, the change in bile acid metabolism
and the respective transporters may provide a new PA toxicity mechanism