Metabolic Profiling of Amino Acids Associated with Mortality in Patients with Acute Paraquat Poisoning

Abstract

BackgroundParaquat is a major cause of fatal poisoning after ingestion in many parts of Asia and the Pacific nations. However, optimal prognostic indicators to evaluate patient mortality have not been unequivocally established. Following acute paraquat poisoning, a number of amino acids (AA), are abnormally expressed in metabolic pathways. However, the alterations in AA metabolite levels after paraquat poisoning remain unknown in humans.Material/MethodsIn the present study, 40 patients were enrolled, of whom 16 survived and 24 died. A metabolomics approach was used to assess changes in AA metabolites in plasma and its potential prognostic value following paraquat poisoning. Mass spectrometry (MS) based on metabolite identification was conducted.ResultsTwenty-five AA levels in plasma were abnormally expressed in non-survivor patients. Among them, creatinine, indolelactate, and 3-(4-hydroxyphenyl)lactate were found to be highly correlated with paraquat death prediction. It was noted that the intensity levels of these 3 AA metabolites in the non-survivor group were substantially higher than in the survivor group. Furthermore, we examined receiver operating characteristic (ROC) curves for clinical validation. ROC results showed that 3-(4-hydroxyphenyl)lactate had the highest AUC of 0.84, while indolelactate and creatinine had AUCs of 0.75 and 0.83, respectively, suggesting that they can be used to predict the clinical outcome (although this methodology is expensive to implement).ConclusionsMetabolic profiling of AA levels could be a reliable tool to identify effective indicators for the early high precision prognosis of paraquat poisoning.

Tetrahydroxy stilbene glycoside attenuates acetaminophen‐induced hepatotoxicity by UHPLC‐Q‐TOF/MS‐based metabolomics and multivariate data analysis

“…The volcano maps of differential metabolites are shown in Figure 6a. Metabolomics focuses on low molecular weight endogenous metabolites in biological samples (Wan et al, 2018) and is a promising tool for identifying novel biomarkers that could help to elucidate the protective mechanisms of TSG by investigating the changes in metabolic signatures induced by APAP exposure. As shown in Figure 6, the black plot shows there is no difference between the model and the control.…”

“…# p < .05, ## p < .01 compared with ctrl; *p < .05, **p < .01 compared with model. TSG, tetrahydroxy stilbene glycoside endogenous metabolites in biological samples (Wan et al, 2018) Pathway analysis has proven to be an invaluable tool in understanding complex relationships among genes and proteins (Goffard et al, 2009;Schmidt et al, 2018). The identify biomarkers responsible for the effect of APAP played an important role in specific metabolic pathways.…”

Microbiome Dysbiosis Shows Strong Association of Gut-Derived Altered Metabolomic Profile in Gulf War Chronic Multisymptom Illness Symptom Persistence Following Western Diet Feeding and Development of Obesity

“…Potential beneficial metabolites were also observed to be increased in the WD group. The metabolite 3-(4-hydroxyphenyl) lactate belongs to tryptophan and tyrosine metabolic pathways, which are natural antioxidants [ 40 ]. N-acetyl aspartate has been used as a biomarker for a healthy human brain and has been shown to be reduced following brain injury [ 41 ].…”

Identification of Serum-Based Metabolic Feature and Characteristic Metabolites in Paraquat Intoxicated Mouse Models

“…Gas chromatography-time-of-flight mass spectrometry (GC-TOF/MS) is one of the most widely used platforms in non-targeted metabolomics studies (Lenz and Wilson, 2007), which provides high chromatographic resolution, high mass measurement accuracy, and rapid spectrum acquisition (Ni et al, 2016). Given the poor prognosis of PQ intoxication, previous studies focused on mining potential prognosis biomarkers from patient samples by either metabolomics or other non-highthroughput approaches (Yeo et al, 2012;Wunnapuk et al, 2013;Wan et al, 2018;Chen et al, 2019a). Relatively few studies paid attention to the metabolic feature caused by PQ exposure to help us investigate the underlying mechanisms, which might contribute to develop new therapeutic targets and diagnosis biomarkers.…”