Biomarkers of oxidative and nitro‐oxidative stress: conventional and novel approaches

Abstract

The concept of oxidative stress (OS) that connects altered redox biology with various diseases was introduced 30 years ago and has generated intensive research over the past two decades. Whereas it is now commonly accepted that macromolecule oxidation in response to ROS is associated with a variety of pathologies, the emergence of NO as a key regulator of redox signalling has led to the discovery of the pathophysiological significance of reactive nitrogen species (RNS). RNS can elicit various modifications of macromolecules and lead to nitrative or nitro-OS. In order to investigate oxidative and nitro-OS in human and in live animal models, circulating biomarker assays have been developed. This article provides an overview of key biomarkers used to assess lipid peroxidation and NO/NO 2 signalling, thereby stressing the necessity to analyse several OS biomarkers in relation to the overall (aerobic) metabolism and health condition of patients. In addition, the potential interest of heart rate variability as the non-invasive integrative biomarker of OS is discussed. LINKED ARTICLESThis article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc Abbreviations 4-HNE, trans-4-hydroxy-2-nonenal; ACR, acrolein; ALE, advanced lipoxidation end-products; DNP, 2,4-dinitrophenylhydrazine; FRR, free radical reaction; HRV, heart rate variability; LO, lipid alkoxyl radical; LOO, lipid peroxyl radical; LOOH, lipid hydroperoxide; LPO, lipid peroxidation; MDA, malondialdehyde; NO + , nitrosonium ion; Nrf2, Nuclear factor (erythroid-derived 2)-like 2; OMP, oxidatively modified protein; OS, oxidative stress; PUFA, polyunsaturated fatty acids; RNS, reactive nitrogen species; TBARS, thiobarbituric acid reactive substances; UPR, unfolded protein response IntroductionOxidative stress (OS), which was first introduced as a concept in redox biology and medicine in 1985 by Helmut Sies and Enrique Cadenas (Cadenas and Sies, 1985;Sies and Cadenas, 1985), has gained increasing interest over the years to become a major field of investigation in chemistry, life sciences and medicine.This concept connects oxidative chemistry with biological stress responses. However, it has the disadvantage of concealing redox chemistry, which plays a key role in cell homeostasis and signalling and in physiology, which is, for a large part, dependent on both oxidation and reduction reactions (Frein et al., 2005). This complex field of biochemistry, which plays a key role in the regulation of a variety of enzymes involved in essential signalling pathways, is now referred to as 'redox signalling' (Ullrich and Kissner, 2006) (Figure 1 et al., 2015). This reaction gives rise to peroxynitrite (ONOO À ), which is a highly reactive nitrogen species (RNS), producing nitration and nitrosation of substrates, often proteins that play important pathophysiological roles (Ullrich and Kissner, 2006;Schulz et al., 2008;Bottari, 20...

Correlation of adenosine deaminase operating under nitro-oxidative stress with tumor and vascularization in patients with advanced gallbladder carcinoma

“…This suggests that under chronic nitro-oxidative stress, sustained purine salvage pathway could enriched developing solid tumors in new vasculatures. Persistent flow of reactive oxygen and nitrogen species (ROS) supplied by the cross talk between iNOS, ADA and XO activities can act as a strong accelerator for GBC progression (Cipak et al, 2017;Espinoza et al, 2016;Waris and Ahsan, 2006).…”

“…Persistent nitro-oxidative stress gives rise to gallbladder inflammation, which could shift chronic cholecystitis into gallbladder carcinoma (Cipak et al, 2017;Espinoza et al, 2016;Waris and Ahsan, 2006). Indeed, up regulation of inducible nitric oxide synthase (iNOS)-releasing nitric oxide (NO), a precursor of reactive oxygen/nitrogen species (ROS) was associated with poor prognosis for cancers of variable origins, including gallbladder (De Oliveira et al, 2017;Thompson et al, 2015).…”

“…The ROS-dependent oxidation of polyunsaturated fatty acids scaffolding membrane lipid bilayer, releases lipid peroxides such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA). These volatile electrophiles bind to DNA and proteins generating stable toxic adducts that contribute to alteration of membrane permeability, mitochondrial dysfunction, apoptosis and cell proliferation (Cipak et al, 2017;Gasparovic et al, 2017;Zhong and Yin, 2015). Their neutralization by thiol-conjugation depletes glutathione (GSH) stores, and alters the protective antioxidant network at both cellular and systemic level (Ramsay and Dilda, 2014;Singhal et al, 2015).…”

Pharmacology of oxidative stress: translational opportunities

“…Finally, Cipak Gasparovic et al () present an overview on the classical markers of nitro‐oxidative stress, namely, protein‐bound 3‐nitrotyrosine, S‐nitrosylated proteins and lipid peroxidation products such as malondialdehyde or 4‐hydroxynonenal, and discuss their usefulness from a clinical perspective. They also critically assess these traditional markers in relation to the overall (aerobic) metabolism and health status of patients, estimated by variations in heart rate and several metabolic parameters (e.g.…”

Efecto de los arándanos sobre el estado oxidativo de la leche en madres con mastitis

“…Esta situación da lugar al llamado "estrés oxidativo" (Betteridge DJ, 2000), que se define como una situación de desequilibrio entre agentes oxidantes y antioxidantes en favor de los primeros (Sies H, 1997 (Hausladen A & Stamler JS, 1999). Esta situación puede ocurrir in vivo en distintas patologías, entre ellas las asociadas a procesos inflamatorios, neurotoxicidad, isquemias o durante la neurotransmisión que tiene lugar mediante activación de receptores NMDA (Klatt P & Lamas S, 2000;Brown GC, 2010;Muriach et al, 2010;Cipak Gasparovic A et al, 2016).…”