Application of UPLC-QTOF-MS in Analysis of Non-targeted Urine Metabolomics in Rats with Yunaconitine Poisoning

Abstract

ObjectiveTo explore the possible mechanism of Yunaconitine poisoning by studying the changes of urine metabolic profile in rats chronically poisoned by Yunaconitine via non-targeted metabolomics.MethodsA rat model of Yunaconitine poisoning was established, and a metabolomics method based on UPLC-QTOF-MS technology was used to obtain the urine metabolic profile. Principal component analysis （PCA）, orthogonal projections to latent structures-discriminant analysis （OPLS-DA）, variable importance in projection （VIP） value greater than 1, fold change （FC） value greater than 3 or less than 0.33 and P value less than 0.05 were used to screen potential biomarkers related to the toxicity of Yunaconitine. The metabolic pathway analysis was performed through the MetaboAnalyst website and pathological changes of related tissues were observed.ResultsSixteen potential biomarkers including L-isoleucine were screened, which mainly involved six metabolic pathways including the biosynthesis and degradation of valine, leucine and isoleucine, pentose and glucuronate interconversions, and propanoate metabolism, alanine, aspartate and glutamate metabolism, tyrosine metabolism. Pathological studies showed that rat toxic change in nervous system, liver and cardiac caused by Yunaconitine.ConclusionYunaconitine may cause neurotoxicity, hepatotoxicity and cardiotoxicity by affecting amino acid and glucose metabolism.

Keywords

• forensic toxicology
• metabolomics
• poisoning
• yunaconitine
• ultra performance liquid chromatography coupled with quadrupole-time of flight-mass spectrometry
• urine
• rats