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 pathogenesis 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. The level of lipoperoxidation positively correlated with the state of BBB (P < 0.05). Elevated concentrations of protein’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 mediated damage to plasma proteins, what was confirmed by their positive mutual 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.
 Noseworthy, J.H. (1991) Progress in determining the causes and treatment of multiple sclerosis. Nature, 399, 40-47.
 Gonsette, R.E. (2008) Neurodegeneration in multiple sclerosis: The role of oxidatvie stress and excitotoxicity. Journal of the Neurological Sciences, 274, 48-53.
 Sayre, L.M., Perry, G. and Smith, M.A. (2008) Oxidative stress and neurotoxicity. Chemical Research in Toxicology, 21, 172-188. http://dx.doi.org/10.1021/tx700210j
 Re, R., Pellegrini, N., Protteggente, A., Pannala, A., Yang, M. and Rice-Evans, C. (1999) Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Biology & Medicine, 26, 1231-1237.
 el-Saadani, M., Esterbauer, H., el-Sayed, M., Goher, M., Nassar, A.Y. and Jurgens, G. (1989) A spectrophotometric assay for lipid peroxides in serum lipoproteins using a commercially available reagent. Journal of Lipid Research, 30, 627-630.
 Buss, H., Chan, T.P., Sluis, K.B., Domigan, N.M. and Winterbourn, C.C. (1997) Protein carbonyl measurement by a sensitive ELISA method. Free Radical Biology & Medicine, 23, 361-366.
 Uttara, B., Singh, A.V., Zamboni, P. and Mahajan, R.T. (2009) Oxidative stress and neurodegenerative diseases: A review of upstream and downstream antioxidant therapeutic options. Current Neuropharmacology, 7, 65-74.
 Besler, H.T. and Comoglu, S. (2003) Lipoprotein oxidation, plasma total antioxidant capacity and homocysteine level in patients with multiple sclerosis. Nutritional Neuroscience, 6, 189-196.
 Miller, E., Mrowicka, M., Saluk-Juszczak, J. and Majsterek, I. (2011) The level of isoprostanes as a non-invasive marker for in vivo lipid peroxidation in secondary progressive multiple sclerosis. Neurochemical Research, 36, 1012-1016.
 Frei, B., Stocker, R. and Ames, B.N. (1988) Antioxidant defences and lipid peroxidation in human blood plasma. Proceedings of the National Academy of Sciences of USA, 85, 9748-9752. http://dx.doi.org/10.1073/pnas.85.24.9748
 Miller, E., Walczak, A., Saluk, J., Ponczek, M.B. and Majsterek, I. (2012) Oxidative modification of patient’s plasma proteins and its role in pathogenesis of multiple sclerosis. Clinical Biochemistry, 45, 26-30.
 Kuracka, L. (2011) Association between degradation products of purine nucleotides in cerebrospinal fluid and levels of some lipofilic vitamins in plasma of patients with multiple sclerosis. Proceedings of the 50th Faculty Conference of Student Science Work, 6th Scientific Conference of Graduants MF CU, 14 April 2011, Bratislava, 67-70.
 Amorini, A.M., Petzold, A., Tavazzi, B., Eikelenboom, J., Keir, G., Belli, A., Giovannoni, G., Di Pietro, V., Polman, C., D’Urso, S., Vagnozzi, R., Uitdehaag, B. and Lazzarino, G. (2009) Increase of uric acid and purine compounds in biological fluids of multiple sclerosis patients. Clinical Biochemistry, 42, 1001-1006.
 Miller, E., Mrowicka, M., Malinowska, K., Mrowicki, J., Saluk-Juszczak, J. and Kedziora, J. (2009) Effects of wholebody cryotherapy on oxidative stress in multiple sclerosis patients. Journal of Thermal Biology, 35, 406-410.
 Virgili, N., Mancera, P., Wappenhans, B., Sorrosal, G., Biber, K., Pugliese, M. and Espinosa-Parrilla, J.F. (2013) KATP channel opener diazoxide prevents neurodegeneration: A new mechanism of action via antioxidative pathway activation. PLoS One, 11, 8-9.
 Sadowska-Bartosz, I., Adamczyk-Sowa, M., Galiniak, S., Mucha, S., Pierzchala, K. and Bartosz, G. (2013) Oxidative modification of serum proteins in multiple sclerosis. Neurochemisty International, 63, 507-516.