Table 3.

Classification of commonly assessed biomarkers of oxidative stress and inflammation in the studies included in the systematic review.

Biological process	Biomarker	Short description (mechanistic pathway)	Interpretation	Referencesa
Reactive oxygen and nitrogen species (RONS)
RONS (e.g., ROMs, NO)		Products and byproducts of biological processes that mediate signal transduction and induce oxidative damage.	↑Oxidative stress	[58,59]
Biomarkers of oxidative damage
Lipid peroxidation	Isoprostanes (F2-Isoprostanes)	Formed by free radical-catalyzed oxidation of arachidonic acid.	↑Oxidative stress	[60]
	Ox-LDL	Originated from oxidative modification hypothesis of atherosclerosis.	↑Oxidative stress	[60]
	Malondialdehyde (MDA)	Reactive aldehyde derived from lipid peroxidation of various polyunsaturated fatty acids that can from DNA- and protein adducts.	↑Oxidative stress	[61,62]
	TBARS	TBA-reactive substances (reactive carbonyl groups–containing compounds) measured as proxy of MDA levels.b	↑Oxidative stress	[61,62]
Oxidative damage to proteins/amino acids	Protein carbonyls	Result of oxidative cleavage of protein backbones.	↑Oxidative stress	[60]
	Nitrotyrosine	Nitration of tyrosine (free amino acid or within a peptide) induced by RNS.	↑Oxidative stress	[60]
Oxidative DNA damage	8-OH-dG	Oxidative stress induced base modification. If not repaired, 8-OH-dG can lead to GC-TA transversion (mutation).	↑Oxidative stress	[60]
Reactive metabolic products and byproducts
Metabolic byproducts	Methylglyoxal	Highly reactive dicarbonyl compound that is a by-product of glycolysis and major cell-permeant precursor of AGEs.	↑Oxidative stress	[63]
Glycoxidation - Protein or lipid become glycation	AGEs (e.g., CML)	Heterogeneous group of molecules formed in a nonenzymatic reaction between reducing sugars and amino groups (lipids, DNA, proteins) during normal metabolism.	↑Oxidative stress	[60]
Antioxidant defense mechanisms (detoxification of ROS)
Superoxide dismutases	SOD1, 2 and 3	A family of metalloenzymes that catalyze the dismutation of two molecules of superoxide anion to hydrogen peroxide and molecular oxygen, functioning as powerful antioxidant in the cells.	↓Oxidative stress	[64]
Catalase system	Catalase	Catalyzes the detoxification of hydrogen peroxide.	↓Oxidative stress	[64]
Glutathione system	GSH	The reduced form of the most important low molecular weight antioxidant synthesized in cells involved in detoxification of reactive substances.	↓Oxidative stress	[65]
	Glutathione reductase	Detoxifies GSSG, a potentially toxic product of the oxidation of GSH.	↓Oxidative stress	[65]
	Glutathione peroxidase	Catalyzes the detoxification of hydrogen peroxide to water, and lipid peroxides to their corresponding alcohols.	↓Oxidative stress	[64]
Thioredoxin system	Thioredoxin reductase	NADPH-dependent reducing enzyme in reactions involving thioredoxin.	↓Oxidative stress	[66]
Paraoxonases	PON1, 2 and 3	Reflect antioxidant activity and play a fundamental role in detoxification of many compounds (e.g., early oxidative products).	↓Oxidative stress	[67]
Heme oxygenases	Heme oxygenase-1	Antioxidant and anti-inflammatory enzyme that is usually expressed at low levels, but that can be highly upregulated in response to oxidative stress (Nrf2-regulated)	↑Oxidative stress	[68]
Antioxidant capacity	TAC	General term that depicts total antioxidant capacity which can be assessed following various approaches.	↓Oxidative stress	[69]
	FRAP	Result of a reaction of sample antioxidants with inorganic oxidants (e.g., Fe3+ or Cu2+), representing rather the reducing capacity.	↓Oxidative stress	[69]
Immune-inflammatory activation as sources of oxidative stress
Immune-system machinery for generating ROS	MPO	Enzyme stored in the granules of neutrophiles that catalyzes the formation of hypochlorous acid from hydrogen peroxide.	↑Oxidative stress	[70,71]
	AOPP	Formed mainly by chlorinated oxidants as a result from activity of myeloperoxidase.	↑Oxidative stress	[72]
	sNOX2-dp	Product of NOX2 activation, an enzyme that plays a role in ROS generation by phagocytic leukocytes.	↑Oxidative stress	[73,74]
	Lipoprotein-associated phospholipase A2	Enzyme secreted from immune cells regulated by cytokines and steroid hormones that can release isoprostanes from esterified phospholipids.	↑Oxidative stress	[75]
Biomarkers of immune-inflammatory pathways
Acute phase reactant	hsCRP	Produced mainly in the liver in response to increase of proinflammatory cytokines that represents a sensitive and nonspecific marker of systemic low-grade inflammation.	↑Inflammation	[76]
Cytokines	IL-6	Produced in response to infections, tissue injuries, hematopoiesis, and other immune reactions. Its dysregulation plays a role in on chronic inflammatory states and autoimmunity.	↑Immune activation	[77]
	TNF-α	Induces inflammation, activation of vascular endothelium, recruitment of immune cells, and tissue destruction and plays a role in chronic inflammation.	↑Immune activation	[78]
	IL-10	Anti-inflammatory function, with a central role in preventing inflammatory and autoimmune diseases.	↓Immune activation	[79]
Adipokines	Adiponectin	Plays a role in various aspects of metabolism and exerts anti-inflammatory activity (e.g., inhibiting phagocytic activity and IL-6 and TNF production).	↓Inflammation	[80]
	Leptin	Plays a role in various aspects of metabolism and exerts pro-inflammatory and immune activation properties.	↑Inflammation	[80]

Abbreviations: AOPP, advanced oxidation protein products; CML, N(6)-carboxymethyllysine; FRAP, ferric reducing ability of plasma; GSSG, glutathione (oxidized); GSH, glutathione (reduced); hsCRP, high-sensitivity C-reactive protein; IL, interleukin; MDA, malondialdehyde; MPO, myeloperoxidase; NADPH, nicotinamide adenine dinucleotide phosphate; NO, nitric oxide; NOX2, NADPH oxidase 2; ox-LDL, oxidized low-density lipoprotein; PON, paraoxonase; ROMs, reactive oxygen metabolites; RONS, reactive oxygen and nitrogen species; sNOX2-dp, soluble NOX2–derived peptide; SOD, superoxide dismutase; TAC, total antioxidant capacity; TBARS, thiobarbituric acid reactive substances; TNF-α, tumor necrosis factor- α; 8-OH-dG; 8-oxo-2′-deoxyguanosine.

^aSelected publications describing mechanistic pathways of biomarkers.

^bTBARS Assay is characterized by low sensitivity and specificity.