Multiple sclerosis (MS) is a chronic, inflammatory, immune-mediated disease of the central nervous system.1 Various mechanisms, such as inflammation, axonal damage, oxidative injury, excitotoxicity, demyelination, and remyelination, are implicated in the pathophysiology of MS.2 Several studies have found increased levels of oxidative stress (OS) biomarkers and/or decreased levels of antioxidants in the blood and cerebrospinal fluid of MS patients.3 The mode of action of some disease-modifying therapies in MS is mediated by their antioxidant properties.4
The aim of our study was to analyse the OS parameters during MS relapse and investigate the effect of corticosteroid (CS) therapy on oxidative status. Sixty relapsing-remitting MS patients, consisting of 36 females and 24 males with an average age of 39.97 years and MS duration of 7.33 years, were enrolled in the study. The control group consisted of 60 healthy individuals matched for age and sex. Levels of pro-oxidative–antioxidative balance (PAB), nitrates and nitrites, total antioxidative status (TAS), paraoxonase, transferrin, bilirubin, and uric acid were measured in the control group and in the MS patient group before (MS1) and 1 day after CS therapy (MS2). While PAB, nitrites, and nitrates are pro-oxidants, TAS, paraoxonase, transferrin, bilirubin, and uric acid are antioxidants. All measurements were completed spectrophotometrically in peripheral blood samples.
In heparinised plasma, PAB, nitrates, and nitrites were significantly higher in patients at baseline with respect to the control group (p<0.0001). Plasma levels of TAS and paraoxonase and serum levels of transferrin, bilirubin, and uric acid showed significantly lower values in MS patients before treatment compared to controls (p<0.0001). After CS treatment, PAB, nitrites, and nitrates were still significantly higher (p<0.0001) in the MS group versus the control group, while TAS, paraoxonase, transferrin, bilirubin, and uric acid were significantly lower (p<0.005) in MS2 versus the control group. When comparing MS1 versus MS2, we found significantly lower values of PAB (p<0.0001), nitrates and nitrites (p<0.005), TAS (p<0.005), paraoxonase (p<0.05), transferrin (p<0.05), bilirubin (p<0.0001), uric acid (p<0.0001), and Expanded Disability Status Scale score (p<0.0001) in MS2. However, we found no correlation between OS parameters and Expanded Disability Status Scale score or between oxidative status and MS duration. CS treatment caused a significant decrease of pro-oxidants and antioxidants in the MS patient group, which correlated with clinical improvement. As it has potent anti-inflammatory and immunosuppressive properties,5 a beneficial effect of CS in relieving OS and lowering pro-oxidants is expected. However, at the same time, CS decreases the cellular antioxidant capacity by suppressing nuclear factor erythroid 2-related factor 2,6 which regulates the antioxidant defence system by inducing expression of antioxidant response element-dependent genes.7
Our findings show the presence of persistent OS in MS patients compared to controls, before and after CS therapy (i.e., unrelated to clinical status). However, CS treatment resulted in the decrease of pro-oxidants, which might be one of the mechanisms underlying clinical improvement. We also found decreased antioxidant activity in MS patients compared to controls and further decrease after CS therapy, unrelated to clinical improvement.
