Metabolomic Study to Determine the Mechanism Underlying the Effects of Sagittaria sagittifolia Polysaccharide on Isoniazid- and Rifampicin-Induced Hepatotoxicity in Mice

Molecules. 2018 Nov 27;23(12):3087. doi: 10.3390/molecules23123087.

Abstract

In this study, a non-targeted metabolic profiling method based on ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was used to characterize the plasma metabolic profile associated with the protective effects of the Sagittaria sagittifolia polysaccharide (SSP) on isoniazid (INH)-and rifampicin (RFP)-induced hepatotoxicity in mice. Fourteen potential biomarkers were identified from the plasma of SSP-treated mice. The protective effects of SSP on hepatotoxicity caused by the combination of INH and RFP (INH/RFP) were further elucidated by investigating the related metabolic pathways. INH/RFP was found to disrupt fatty acid metabolism, the tricarboxylic acid cycle, amino acid metabolism, taurine metabolism, and the ornithine cycle. The results of the metabolomics study showed that SSP provided protective effects against INH/RFP-induced liver injury by partially regulating perturbed metabolic pathways.

Keywords: Sagittaria sagittifolia polysaccharide; isoniazid; liver injury; rifampicin; ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS).

MeSH terms

  • Animals
  • Chemical and Drug Induced Liver Injury* / metabolism
  • Chemical and Drug Induced Liver Injury* / prevention & control
  • Isoniazid / adverse effects*
  • Isoniazid / pharmacology
  • Metabolome / drug effects*
  • Metabolomics
  • Mice
  • Mice, Inbred BALB C
  • Polysaccharides / chemistry
  • Polysaccharides / pharmacology*
  • Rifampin / adverse effects*
  • Rifampin / pharmacology
  • Sagittaria / chemistry*

Substances

  • Polysaccharides
  • Isoniazid
  • Rifampin