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

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.

Protective Effects of Naringenin from Citrus sinensis (var. Valencia) Peels against CCl4-Induced Hepatic and Renal Injuries in Rats Assessed by Metabolomics, Histological and Biochemical Analyses

“…Furthermore, the liver plays a significant role in fatty acid metabolism because it absorbs a high amount of free FAs (FFAs), accessing the splanchnic bed through the portal vein [ 57 ], whereas the non-hepatic splanchnic bed absorbs only a tiny fraction of FFAs. When the liver’s FA metabolism is insufficient, FFA levels in the blood and uptake by the liver increase, resulting in lipid deposition in liver cells and cytotoxicity [ 58 ]. Under normal conditions, mitochondria may deconstruct large amounts of FAs in cells and make ATP via FA beta-oxidation production, despite the electron respiratory chain leading to extreme production of reactive oxygen species (ROS) [ 44 ].…”

Gut microbiome dysbiosis in patients with hepatitis B virus-related hepatocellular carcinoma after extended hepatectomy liver failure

“…In addition, organic acid metabolism pathways (acetyl-CoA fermentation to butanoate II and pyruvate fermentation to propanoate I), pyrimidine metabolism pathways, palmitate biosynthesis, and stearate biosynthesis were all increased. Amino acid metabolism only functions in the liver, and any disease or injury, such as hepatitis B, cirrhosis, and hepatic encephalopathy, is inevitably accompanied by amino acid balance disorders (44)(45)(46). For instance, arginine reduction is a specific biomarker for acute liver injury (47); lysine exhibits strong free radical scavenging activities, inhibits free radical-mediated damage, and protects against liver injury (48,49); and decreased alanine inhibits gluconeogenesis and leaves the glucose-dependent liver at risk of energy deprivation, ultimately leading to damage (50,51).…”

1H-NMR Metabolomics Analysis of the Effect of Rubusoside on Serum Metabolites of Golden Hamsters on a High-Fat Diet

“…Similar to the PCA score map, ND and HFD were well separated from each other, whereas HFD+PRbs and HFD+Rbs partially overlapped and were more closely related to ND ( Figure 3B). After normalizing the obtained data with the Pareto scaling method [23,24], we analyzed the data with unsupervised principal component analysis (PCA), a multivariate statistical method which reduces the number of observations through dimensionality reduction into a few comprehensive indicators while it preserves the main information of the original variables ( Figure 3A). PC 1 and 2 explain 36.2% and 19.5% of the metabolic variance of serum, respectively.…”