Oxidative Modification of Blood Serum Proteins in Multiple Sclerosis after Interferon Beta and Melatonin Treatment

Abstract

Multiple sclerosis (MS) is a disease involving oxidative stress (OS). This study was aimed at examination of the effect of melatonin supplementation on OS parameters, especially oxidative protein modifications of blood serum proteins, in MS patients. The study included 11 control subjects, 14 de novo diagnosed MS patients with the relapsing-remitting form of MS (RRMS), 36 patients with RRMS receiving interferon beta-1b (250 μg every other day), and 25 RRMS patients receiving interferon beta-1b plus melatonin (5 mg daily). The levels of N′-formylkynurenine, kynurenine, dityrosine, carbonyl groups, advanced glycation products (AGEs), advanced oxidation protein products (AOPP), and malondialdehyde were elevated in nontreated RRSM patients. N′-Formylkynurenine, kynurenine, AGEs, and carbonyl contents were decreased only in the group treated with interferon beta plus melatonin, while dityrosine and AOPP contents were decreased both in the group of patients treated with interferon beta and in the group treated with interferon beta-1b plus melatonin. These results demonstrate that melatonin ameliorates OS in MS patients supporting the view that combined administration of interferon beta-1b and melatonin can be more effective in reducing OS in MS patients than interferon beta-1b alone.

Monitoring the Redox Status in Multiple Sclerosis

“…The plasma carbonyl levels were elevated in SPMS and correlated with the EDSS and the Beck Depression Inventory [ 208 ]. The levels of carbonyl groups were elevated in serum of patients with RRMS and lowered in the group of RRMS patients treated with INF-β [ 74 ]. The levels of CSF carbonyl proteins measured were elevated in RRMS and progressive MS [ 209 , 210 ] ( Table 3 and Table 4 ).…”

“…Oxidative environments generate oxidized tyrosine orthologues such as o-tyrosine, m-tyrosine, nitrotyrosine, and dityrosine. Dityrosine was elevated in serum of RRMS patients [ 73 , 74 ]. Advanced oxidation protein products (AOPPs) are uremic toxins produced in reaction of plasma proteins with chlorinated oxidants such as chloramines and hypochlorous acid (HClO) [ 212 ].…”

“…Furthermore, the levels of AOPPs were significantly higher in patients with higher EDSS scores than lower ones [ 50 ]. The AOPPs levels were decreased in serum of RRMS patients treated with IFN-β [ 74 ] ( Table 3 and Table 4 ).…”

“…The AGEs can accumulate in tissues and body fluids, resulting in protein malfunctions, reactive chemical production, and inflammation [ 214 ]. The levels of AGEs were significantly elevated in serum of RRMS patients, but no significant change was observed after IFN-β treatment [ 74 ]. The concentrations of AGEs were significantly higher in brain samples of MS patients, compared to nondemented counterparts.…”

Monitoring the Redox Status in Multiple Sclerosis

“…The uric acid levels were significantly lower in active MS than inactive MS, and the uric acid levels were independently correlated with gender, disease activity and duration of the disease [46] (Table 3). [62,180,193] Advanced glycation end products (AGEs) ↑ ↑ [180,193] Amino acids Asymmetric dimethylarginine (ADMA) ↓ - [195] Lipid F2-isoprostane (F2-isoP) ↑ ↑ [198][199][200][201][202] Malondialdehyde [127] deoxyguanosine (8-oxodG) The plasma membrane is a network of phospholipid bilayer and integral proteins, which protects the cellular organelles from the outer environment and responsible for several cellular functions such as cell adhesion, ion transport, cell signaling and phagocytosis. The main ROS of the plasma membrane is superoxide (O2 −• ) produced by the membrane-bound enzyme nicotinamide adenine dinucleotide phosphate oxidase (NOX) which is composed of two membrane proteins, three cytosolic proteins, and a small GTP-binding protein [47,48].…”