New Insights into the Role of Oxidative Stress Mechanisms in the Pathophysiology and Treatment of Multiple Sclerosis

Table 1

Biomarkers of oxidative stress. Free radicals can damage biological molecules including nucleic acids, proteins, carbohydrates, and lipids with the participation of various enzymes. As a result of these reactions new compounds are formed which may become biomarkers. Most of the available biological materials can be used to measure the level of these compounds in MS patients.

(a)

The biological material: serum
Enzyme	Reference	Lipid damage	Reference	Protein damage	Reference	RNA/DNA damage	Reference	Carbohydrate damage	Reference	Other	Reference
Xanthine oxidase	[8]	Isoprostanes	[5]	Nitrotyrosine	[5, 9]	8-Hydroxy-2′-deoxy guanosine	[10]	Fructosamine	[11]	Peroxynitrite	[12]
NADPH dependent oxidase	[13]	MDA	[5, 14, 15]	O-Tyrosine	[9]					TOS	[16, 17]
Monoamino oxidase	[18]	Fluorescent peroxidized lipid-protein covalent adducts	[19, 20]	Glycophore	[21]					OSI	[17]
Alpha-ketoglutarat dehydrogenase	[18]	CL-LOOH	[22]	AOPP	[21–27]					Thiobarbituric acid reacting substances	[11]
Glycerol phosphate dehydrogenase	[18]	Conjugated diene	[19]	Protein carbonyls	[21, 22]					α-2-Macroglobulin	[13]
Lipoxygenase	[10]			Dityrosine	[21]					Acrolein	[28]
Cyclooxygenase	[10]			N′-Formylkynurenine	[21, 29]					Schiff bases	[30]
Myeloperoxidase	[10]			Kynurenine	[29]					Lipophilic fluorescent end-CL-products	[20]
Prolyl oligopeptidase	[31]			Decreased proteins thiol groups	[21, 32]					Tert-Butyl; hydroperoxide-initiated; chemiluminescence	[26]
Nitric oxide synthase	[31]									2′,7′-Dichlorodi: hydrofluorescein: diacetate fluorescence	[33]
										NOx	[22]
										CCL11	[34]
										IL-6	[22, 26]
										IL-17	[22, 26]
										TNF-α	[22]
										IFN-γ	[22]
										IL-4	[22]
										IL-10	[22]

(b)

The biological material
	CSF	References	Erythrocyte	References	Urine	References	Saliva	References
Lipid damage	Isoprostanes; 8-iso-PGF2α; MDA	[35–37]; [38]; [35–37]	MDA	[24, 25]	8-Iso-PGF2α	[39]
Protein damage	AOPP; Total thiol groups	[21, 23]; [21, 23]	AOPP	[24, 25]			Advanced glycation; end-products	[11]
Other	Ceramides; CCL11	[40]; [34]			3-Hydroxy; propyl-mercapturic acid; (acrolein metabolic)	[28]	Thiobarbituric acid reacting substances	[11]

SOD: superoxide dismutase, NOX1: nicotinamide adenine dinucleotide phosphate-oxidase 1, MDA: malondialdehyde, CL-LOOH: lipid hydroperoxides, NOx: nitric oxide metabolites, TOS: total oxidant status, OSI: oxidative stress index, TNF-α: tumor necrosis factor, IFN-γ: interferon γ, AOPP: advanced oxidation protein products, 8-iso-PGF2α: isoprostane, CCL11: chemokine 11, and CSF: cerebrospinal fluid.