Species differences in bile acids I. Plasma and urine bile acid composition

Rhishikesh Thakare, Jawaher Abdullah Alamoudi, Nagsen Gautam, A. David Rodrigues, Yazen Alnouti

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Maintenance of bile acid (BA) homeostasis is essential to achieve their physiologic functions and avoid their toxic effects. The marked differences in BA composition between preclinical safety models and humans may play a major role in the poor prediction of drug-induced liver injury using preclinical models. We compared the composition of plasma and urinary BAs and their metabolites between humans and several animal species. Total BA pools and their composition varied widely among different species. Highest sulfation of BAs was observed in human and chimpanzee. Glycine amidation was predominant in human, minipig, hamster and rabbit, while taurine amidation was predominant in mice, rat and dogs. BA profiles consisted primarily of tri-OH BAs in hamster, rat, dog and mice, di-OH BAs in human, rabbit and minipig, and mono-OH BA in chimpanzee. BA profiles comprised primarily hydrophilic and less toxic BAs in mice, rat, pig and hamster, while it primarily comprised hydrophobic and more toxic BAs in human, rabbit and chimpanzee. Therefore, the hydrophobicity index was lowest in minipig and mice, while it was highest in rabbit, monkey and human. Glucuronidation and glutathione conjugation were low in all species across all BAs. Total concentration of BAs in urine was up to 10× higher and more hydrophilic than plasma in most species. This was due to the presence of more tri-OH, amidated, sulfated and primary BAs, in urine compared to plasma. In general, BA profiles of chimpanzee and monkeys were most similar to human, while minipig, rat and mice were most dissimilar to human.

Original languageEnglish (US)
Pages (from-to)1323-1335
Number of pages13
JournalJournal of Applied Toxicology
Volume38
Issue number10
DOIs
StatePublished - Oct 2018

Keywords

  • Bile acids
  • Drug induced liver injury
  • Human, Preclinical species
  • LC–MS/MS
  • Plasma
  • Urine

ASJC Scopus subject areas

  • Toxicology

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