2.1.4. Reactive Carbonyl/Halogen/Selenium Species

Reactive carbonyl species (RCS) are metabolically generated highly reactive molecules with aldehydes and electronically excited (3L=O\*) triplet carbonyls, known for their harmful reactions to nucleic acids, proteins, and lipids [92]. In addition, RCS are considered to participate in electrophilic signaling of adaptive cell response and post-transcriptional protein modification [151]. RCS are classified into α,β-unsaturated aldehydes; keto-aldehyde and di-aldehydes. In the presence of catalase and bicarbonate, XO was found to produce the strong one-electron oxidant carbonate radical anion from oxidation with acetaldehyde. The carbonate radical was likely produced in one of the enzyme's redox centers with a peroxymonocarbonate intermediate [45]. Self-reaction of lipid peroxyl radical (LOO•) produced by the oxidation of polyunsaturated fatty acids (PUFAs) by hydroxyl radical (HO•) generates electronically excited triplet carbonyls (3L=O\*) yielding to singlet oxygen (O2 <sup>1</sup>Δg) [89] (Table 2). RCS react with amines and thiols leading to advanced glycation end products (AGEs), biomarkers of ageing and degenerative diseases [152].

MPO, a lysosomal heme-containing enzyme present in granulocytes and monocytes catalyzes the conversion of hydrogen peroxide (H2O2) and chloride anion (Cl<sup>−</sup>) to hypochlorous acid (HClO) during the respiratory burst. An adipocyte producing hormone leptin stimulates the oxidative burst [153]. MPO also oxidizes tyrosine to tyrosyl radical [154]. MPO mediates protein nitrosylation, forming 3-chlorotyrosine (3-Cl-Tyr) and dityrosine crosslinks [155,156] (Table 2).

Studies on MPO activity reported mixed results. The mean MPO activity of peripheral leukocyte was observed reduced in a mixed population of MS patients, compared to controls [157]. Significantly higher serum MPO activity was measured in opticospinal phenotype (OSMS) of RRMS at relapse and remission and in conventional phenotype of RRMS at remission, compared to controls. A positive correlation was associated between Kurtzke's EDSS and MPO activity at remission of OSMS [158] (Table 4). The mean MPO activity of peripheral leukocytes was found higher, but statistically not significant in RRMS, compared to controls [56] (Table 3). No study regarding CSF MPO activity in MS was found. Selenium is an essential micronutrient with similar chemical and physical properties to sulfur, but more easily oxidized and kinetically more labile than sulfur. Selenium is a component of proteinogenic selenocysteine, naturally occurring selenomethionine and selenoproteins, such as glutathione peroxidase (GPx), thioredoxin reductase (TRXR), and selenoprotein P [57]. Reactive selenium species (RSeS) are selenium-containing inorganic and organic compounds including selenite (O3Se<sup>−</sup>2), selenocysteine (C3H7NO2Se), and selenomethionine (C5H11NO2Se) [58] (Table 2). Selenium have both beneficial and harmful actions. At low concentration it works as an antioxidant, inhibiting lipid peroxidation and detoxifying ROS as a component of GPx and TRXR, while at high concentration it becomes a toxic pro-oxidant, generating ROS, inducing lipid oxidation and forming cross-linking in thioproteins [159] (Table 2). The serum selenium levels were measured significantly lower in MS patients, compared to controls, suggesting antioxidant capacity is impaired in MS [160] (Table 3).
