Metabolic profiling of 19 amino acids in triptolide-induced liver injured rats by gas chromatography-triple quadrupole mass spectrometry

Abstract

The liver is an important organ for amino acid metabolism, and its damage can be reflected in the changes of amino acid level in the body. Triptolide (TP) has broad anti-inflammatory and anti-tumor activities, but its clinical application is limited due to hepatotoxicity. In this work, a simple, accurate and sensitive gas chromatography-triple quadrupole mass spectrometry (GC-QqQ-MS/MS) method was developed and validated for evaluating the serum levels of amino acids from control and TP-induced liver injured rats, and chemometric analysis was employed for amino acid metabolic profiles analysis. It was found that 11 amino acids showed significant changes after TP administration, and they were mainly involved in 5 metabolic pathways that are phenylalanine, tyrosine and tryptophan biosynthesis, alanine, aspartate and glutamate metabolism, glutamine and glutamate metabolism, phenylalanine metabolism and arginine biosynthesis. Five amino acids including tyrosine, glutamine, glutamic acid, tryptophan and alanine were identified as biomarkers of TP hepatotoxicity by further analysis. These results indicated that the novel amino acid metabolic profiling study based on the GC-QqQ-MS/MS provided not only exact concentrations of serum amino acids, but also a prospective methodology for evaluation of chemically induced liver injury.

Integrated analysis of metabolomic and gut microbiota reveals idiosyncratic drug-induced liver injury resulting from the combined administration of bavachin and icariside II

“…Indole-3-acetate, closely associated with Bifidobacterium and Bacteroides [39] , requires further investigation to understand its relationship with inflammation or liver injury. The liver's vital role in amino acid metabolism influences various diseases, including liver injury, cardiovascular disease, and diabetes [40][41][42] . Gly is an amino acid that benefits the liver by protecting liver cells and reducing damage [43][44][45] .…”

Arecoline-Induced Hepatotoxicity in Rats: Screening of Abnormal Metabolic Markers and Potential Mechanisms

“…In general, tryptophan has three metabolic pathways, namely the Kynurenine pathway, the 5-hydroxytryptamine pathway, and the indole pathway. Existing studies have confirmed that tryptophan has many biological activities, such as regulating growth, regulating immunity, and anti-oxidative stress [ 38 , 39 ]. In the liver, tryptophan is involved in the synthesis of proteins, and when a toxic injury occurs in the liver, the serum tryptophan level decreases, which in turn promotes the release of pro-inflammatory cytokines and apoptosis, exacerbating hepatic inflammatory response [ 40 ].…”

Investigation of Gynura segetum root extract (GSrE) induced hepatotoxicity based on metabolomic signatures and microbial community profiling in rats

“…Pentose and glucuronate interconversions, alanine, aspartate and glutamate metabolisms, and arginine and proline metabolisms were the common pathways in the lowdose and high-dose groups. Alanine, aspartate, and glutamate metabolisms were both time-and dose-related pathways, which have been proved to be closely related to the mechanism of drug toxicity according to Hu et al (2021a).…”