Evaluation of oxidative and nitrosative stress in relapsing remitting multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS) through demyelination and neurodegeneration. Several lines of evidence support a role for oxidative and nitrative stress (OS and NS) in patho genesis of multiple sclerosis. The mechanism of influence of OS and NS on blood-brainbarrier (BBB) has critical importance for evaluating antioxidant therapies. As far as we know, markers of oxidative and nitrative stress in MS patients have been investigated independently for their relationship with the state of the blood-brain-barrier. Blood plasma samples of 58 patients with relapse-remitting MS (RRMS) with normal (Group A, n = 48, 36.2 ± 10.5 years) and damaged BBB (Group B, n = 10, 38.2 ± 11.2 years) and of 44 healthy controls (39.2 ± 14.9 years) were analyzed. TAS (total antioxidant plasma status), lipoperoxides, protein carbonyls, 3-nitrotyrosine and uric acid were evaluated in each group. Our results confirmed decreased TAS (Group A: 1.35 ± 0.55 mmol/l, P < 0.001; Group B: 1.73 ± 0.37 mmol/l vs. 1.9 ± 0.7 mmol/l) and increased lipoperoxidation (A: 71.5 ± 42.18 nmol/ml, P < 0.01; B: 127.02 ± 74.67 nmol/ml, P < 0.001 vs. 46.6 ± 27.4 nmol/ml) in RRSM patients. Th e level of lipoperoxidation positively correlated with the state of BBB (P < 0.05). Elevated concentrations of protei n’s carbonyls (A: 0.48 ± 0.11 nmol/mg protein, P < 0.001; B: 0.43 ± 0.14 nmol/mg protein, P < 0.05 vs. 0.31 ± 0.01 nmol/ mg protein) and 3-nitrotyrosine (A: 107.3 ± 40.7 nmol/l, P < 0.001; B: 89.2 ± 15.9 nmol/l, P < 0.001 vs. 21.6 ± 3.7 nmol/l) indicated free-radical mediat ed damage to plasma proteins, what was confirmed by their positive mu tual correlation (P < 0.001). The level of uric acid was physiological and correlated negatively with protein’s carbonyls (P < 0.05) while there was no significant relationship with 3-nitotyrosine. The results suggest the role of this antioxidant in the protection of the proteins against OS what was confirmed by its positive correlation with TAS (P < 0.05). It could be concluded that ROS/RNS in MS patients affect a wide range of substances, change their properties and function. High concentration of lipoperoxides indicates a role of lipid peroxidation in deterioration of BBB. Considering the body complexity, extremely high levels of damaged proteins in blood plasma and abnormal state of BBB should lead us to assumption of changed proteins in CNS that can activate immune system and result into autoimmune response. Therefore, it is necessary to pay attention to ROS/RNS reduction in therapeutic process to reduce damage to BBB and other adverse effects.