ABSTRACT
Metabolomics significantly impacts drug discovery and precise disease management. This study meticulously assesses the metabolite profiles of cells treated with Crocin, Dexamethasone, and mesenchymal stem cells (MSCs) under oxidative stress induced by 2-chloroethyl ethyl sulfide (CEES). Gas chromatography/mass spectrometry (GC/MS) analysis unequivocally identified substantial changes in 37 metabolites across the treated groups. Notably, pronounced alterations were observed in pathways associated with aminoacyl-tRNA biosynthesis and the metabolism of aspartate, serine, proline, and glutamate. These findings demonstrate the potent capacity of the analyzed treatments to effectively reduce inflammation, mitigate reactive oxygen species production, and enhance cell survival rates. SIGNIFICANCE.
Subject(s)
Carotenoids , Mesenchymal Stem Cells , Metabolomics , Mustard Gas , Carotenoids/pharmacology , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Metabolomics/methods , Mustard Gas/analogs & derivatives , Mustard Gas/toxicity , Mustard Gas/pharmacology , Oxidative Stress/drug effects , Animals , Humans , Metabolome/drug effects , Reactive Oxygen Species/metabolism , Epithelial Cells/drug effects , Epithelial Cells/metabolismABSTRACT
The present study aimed to evaluate serum prooxidant -antioxidant balance (PAB) in an Iranian population exposed to sulfur mustard (SM) more than 20 years ago. In this study, 42 SM-exposed subjects and 30 unexposed subjects (as controls) were recruited. Serum PAB, biochemical, and hematological parameters were measured in all subjects. Correlation of PAB with biochemical and hematological parameters was determined. The mean PAB values in the SM-exposed group (82.5 ± 34.8 HK) were significantly higher than that in the control group [47.5 ± 17.8 HK] (p < 0.001). The results demonstrated that serum PAB values were positively correlated with alkaline phosphatase activities in the SM-exposed group. Furthermore, PAB values showed a significant negative correlation with hepatic enzymes (AST, ALT), triglycerides, total bilirubin, and mean corpuscular hemoglobin concentrations. PAB values showed a borderline significant negative correlation with uric acid. The present results suggest that late oxidative stress and alterations in biochemical and hematological parameters may be a consequence of the frequent respiratory infections rather than direct toxic effects of SM.
Subject(s)
Antioxidants/metabolism , Chemical Warfare Agents/toxicity , Lung Diseases/chemically induced , Mustard Gas/toxicity , Oxidants/blood , Veterans , Aged , Case-Control Studies , Humans , Iran , Lung Diseases/blood , Lung Diseases/metabolism , Male , Middle Aged , Oxidative Stress/drug effects , Severity of Illness IndexABSTRACT
Sulfur mustard (SM) is a vesication chemical warfare agent for which there is currently no antidote. Despite years of research, there is no common consensus about the pathophysiological basis of chronic pulmonary disease caused by this chemical warfare agent. In this study, we combined chemometric techniques with nuclear magnetic resonance (NMR) spectroscopy to explore the metabolic profile of sera from SM-exposed patients. A total of 29 serum samples obtained from 17 SM-injured patients, and 12 healthy controls were analyzed by Random Forest. Increased concentrations of seven amino acids, glycerol, dimethylamine, ketone bodies, lactate, acetate, citrulline and creatine together with the decreased very low-density lipoproteins (VLDL) levels were observed in patients compared with control subjects. Our study reveals the metabolic profile of sera from SM-injured patients and indicates that NMR-based methods can distinguish these patients from healthy controls.
Subject(s)
Lung Diseases/chemically induced , Metabolome/drug effects , Metabolomics/methods , Mustard Gas/toxicity , Adult , Amino Acids/blood , Biomarkers/blood , Case-Control Studies , Chemical Warfare Agents , Female , Humans , Lipoproteins, VLDL/blood , Lung Diseases/blood , Magnetic Resonance Spectroscopy , Male , Middle Aged , Mustard Gas/pharmacologyABSTRACT
Sulfur mustard (SM) is a potent alkylating agent and its effects on cells and tissues are varied and complex. Due to limitations in the diagnostics of sulfur mustard exposed individuals (SMEIs) by noninvasive approaches, there is a great necessity to develop novel techniques and biomarkers for this condition. We present here the first nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC/MS) metabolic profiling of serum from and healthy controls to identify novel biomarkers in blood serum for better diagnostics. Of note, SMEIs were exposed to SM 30 years ago and that differences between two groups could still be found. Pathways in which differences between SMEIs and healthy controls are observed are related to lipid metabolism, ketogenesis, tricarboxylic acid (TCA) cycle and amino acid metabolism.