Metabolomics of Oxidative Stress in Recent Studies of Endogenous and Exogenously Administered Intermediate Metabolites

Abstract

Aerobic metabolism occurs in a background of oxygen radicals and reactive oxygen species (ROS) that originate from the incomplete reduction of molecular oxygen in electron transfer reactions. The essential role of aerobic metabolism, the generation and consumption of ATP and other high energy phosphates, sustains a balance of approximately 3000 essential human metabolites that serve not only as nutrients, but also as antioxidants, neurotransmitters, osmolytes, and participants in ligand-based and other cellular signaling. In hypoxia, ischemia, and oxidative stress, where pathological circumstances cause oxygen radicals to form at a rate greater than is possible for their consumption, changes in the composition of metabolite ensembles, or metabolomes, can be associated with physiological changes. Metabolomics and metabonomics are a scientific disciplines that focuse on quantifying dynamic metabolome responses, using multivariate analytical approaches derived from methods within genomics, a discipline that consolidated innovative analysis techniques for situations where the number of biomarkers (metabolites in our case) greatly exceeds the number of subjects. This review focuses on the behavior of cytosolic, mitochondrial, and redox metabolites in ameliorating or exacerbating oxidative stress. After reviewing work regarding a small number of metabolites—pyruvate, ethyl pyruvate, and fructose-1,6-bisphosphate—whose exogenous administration was found to ameliorate oxidative stress, a subsequent section reviews basic multivariate statistical methods common in metabolomics research, and their application in human and preclinical studies emphasizing oxidative stress. Particular attention is paid to new NMR spectroscopy methods in metabolomics and metabonomics. Because complex relationships connect oxidative stress to so many physiological processes, studies from different disciplines were reviewed. All, however, shared the common goal of ultimately developing “omics”-based, diagnostic tests to help influence therapies.

Metabolomic Analysis of Anti-Hypoxia and Anti-anxiety Effects of Fu Fang Jin Jing Oral Liquid

“…Under hypoxic conditions anaerobic glycolysis begins to play a dominant role for ATP production, and pyruvate is converted into lactate in the cytoplasm instead of going into the TCA cycle in mitochondria. Hypoxic stress down-regulates oxygen-dependent glycolysis of glucose and triggers mitochondrial oxidative stress [31–33]. To determine if the hypobaric hypoxia mice model was successfully set up, relative quantitative analysis of 28 identified metabolites from brain tissues of HS and F groups was applied.…”

Oxidative Stress and Inflammation Induced by Environmental and Psychological Stressors: A Biomarker Perspective

“…(27)), and broader implication in pathways identified by cross-omics analysis (13,142). Additionally, a comprehensive survey focused on the role of metabolome studies in characterising oxidative studies was previously published by Liu et al (90).…”

Recent trend in risk assessment of formaldehyde exposures from indoor air

“…In rats and mice, stress induced by immobilization or surgery decreased testosterone and increased corticosterone levels (McGrady 1984). In general, terrestrial animal tissue exposed to prolonged fasting, hypoxia and ischaemia/reperfusion responds with oxidative stress and tissue damage (Liu et al 2011; Vázquez-Medina et al 2012), which at least partly depend on the tissue antioxidant level (Vázquez-Medina et al 2012). Thus, hypoxia due to chronic obstructive pulmonary diseases in men decreased serum testosterone levels (Aasebø et al 1993) and caused atrophy of the testosterone producing Leydig cells (Gosney 1987).…”