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

Xiu-Hui Ke,Jing Wang,Chun-Guo Wang,Jun-Ping Lv,Dong-Yu Ge,Yue Han,Wei-Zao Luo,Ya-Jie Yang,Hong-Shuang Liu,Rui-Juan Dong,Yi-Chen Wang,Yan Liao,Re-Yila Tu-Erxun,Bing Li

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.

Highlights

Tuberculosis is a pandemic chronic infectious disease caused by Mycobacterium tuberculosis.Each year, about 9 million people are diagnosed with tuberculosis worldwide, and about 2 million tuberculosis patients die [1]
INH and RFP (INH/RFP) was found to disrupt metabolism related to energy demand
partial least squares (PLS)-DA-mediated classification for the selection and validation of biomarkers revealed 14 metabolites that could be considered as potential biomarkers

Summary

Introduction

Tuberculosis is a pandemic chronic infectious disease caused by Mycobacterium tuberculosis.Each year, about 9 million people are diagnosed with tuberculosis worldwide, and about 2 million tuberculosis patients die [1]. Tuberculosis is a pandemic chronic infectious disease caused by Mycobacterium tuberculosis. Isoniazid (INH) and rifampicin (RFP) are the first-line antituberculosis drugs recommended by the World Health Organization. These two drugs are metabolized in the liver, and both INH and RFP (INH/RFP) cause hepatotoxicity [2]. INH/RFP causes irreversible damage, including liver failure, cell necrosis, inflammation, and steatosis [4,5,6]. These effects are considered to be mainly associated with oxidative stress [7], since INH

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