The cerebrospinal fluid values of advanced oxidation protein products and total thiol content in patients with amyotrophic lateral sclerosis.

OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is recognized as a progressive neurodegenerative disorder of unknown origin. Oxidative stress (OS) is considered as one of the most challenging hypothesis in the disease pathogenesis. The aim of this study was to contribute to the understanding of what extent there is involvement of OS in ALS. PATIENTS AND METHODS: We assessed Advanced Oxidation Protein Products (AOPP) and total thiol (-SH) groups in cerebrospinal fluid (CSF) of 24 ALS patients (13 of them presented with spinal form while 11 patients had bulbar form) and 20 controls (CG). RESULTS: The obtained AOPP levels in ALS patients were higher than those in CG (p <0.001), while -SH groups showed lower values compared to CG (p<0.001). The AOPP values were higher in ALS patients with bulbar compared with ALS patients with common spinal manifestation (p<0.001). There were no differences in -SH group's levels among these different clinical forms (p>0.05). The negative correlation between AOPP and the levels of -SH groups was confirmed (p <0.01). Significant mild correlations between tested parameters and functional rating scale as well as disease progression index were recorded for both of tested parameters in spinal form of ALS (p<0.01). CONCLUSION: The data presented here clearly support the fact that OS is involved in patophysiology of ALS, where oxidation of -SH groups represents an important aspect of protein oxidation. The CSF AOPP level and -SH groups may serve as potential useful biomarker for functional disorder and progression of the disease in the spinal form of ALS.

Relation between plasmatic and cerebrospinal fluid oxidative stress biomarkers and intrathecal Ig synthesis in Multiple Sclerosis patients.

The aim of this study was to evaluate if cerebrospinal fluid (CSF) oxidative stress biomarkers were related to plasmatic levels and to intrathecal Ig synthesis in 51 patients with Multiple Sclerosis (MS) or clinically isolated syndrome (CIS). Plasmatic and CSF ferric reducing ability (FRA) showed a significant positive correlation (ρ 0.28, p=0.04), while advanced oxidation protein products (AOPPs) did not. A negative correlation was found between IgG synthesis index and CSF FRA levels. No difference in CSF AOPPs or FRA was observed between patients with and without intrathecal IgM synthesis. Our results indicate that plasmatic and CSF FRA are strictly linked, while CSF oxidative stress biomarkers are not related to intrathecal Ig synthesis.

The patients with clinically isolated syndrome and relapsing remitting multiple sclerosis show different levels of advanced protein oxidation products and total thiol content in plasma and CSF.

Advanced oxidation protein products (AOPP) and total thiol (SH) groups levels in plasma and CSF were studied in a cohort of 50 clinically isolated syndrome (CIS) and 57 relapsing remittent multiple sclerosis (RRMS) patients related to 20 control group (CG) patients' values. The obtained results were compared regarding patients demographic, biochemical, clinical (EDSS) and MRI features (total T2 weighted lesions number and Gd enhancement lesion volume). Plasma and CSF AOPP levels in CIS and RRMS patients were higher than those in CG, while SH groups showed lower values compared to CG (p<0.05). Both parameters were higher in CIS than in RRMS patients (p<0.05). Related to EDSS median range, all patients were divided into those with slight or mild and those with severe clinical presentation. AOPP and SH group changes were more pronounced in both, CIS and RRMS patients with higher, compared to those with lower EDSS (p<0.05). AOPP, SH group levels and EDSS positive correlations were observed in both study groups (p<0.01). Both parameters showed the same approach regarding the median range of total T2 weighted lesions and Gd enhancement lesion volume mean values (p<0.05), but no correlation was found between AOPP and SH levels and these patients radiological characteristics (p>0.01). The data support the fact that oxidative stress is always involved in CIS and RRMS pathophysiology, but not always as a disease determinant dependent on its intensity, which might be important for new therapeutic strategies based on antioxidant approach in those patients.

May serum levels of advanced oxidized protein products serve as a prognostic marker of disease duration in patients with idiopathic Parkinson's disease?

Protein and amine halogenation is a type of oxidative stress induced by phagocytic overstimulation, and its role in Parkinson's disease (PD) has not been discerned. We have detected that advanced oxidized protein products, markers of protein halogenation, are reliably enhanced in serum of patients with PD (n=60) relative to control subjects (n=45, p<0.012), and to a lesser extent in the cerebrospinal fluid. Amine halogenation, as evaluated through 3-chlorotyrosine, is not affected. Mieloperoxidase and hydrogen peroxide levels, halogenative factors of phagocytes, are devoid of changes. Levels of advanced oxidized protein products are progressively reduced over time, and the duration of PD is larger in the Hoehn-Yahr-stage-2/3 patients (n=34) with low serum levels (R(2)=0.0145, p<0.003). Levodopa treatment contributes to this reduction (R(2)=0.259, p<0.001). These protein products are not cytotoxic, unlike 3-chlorotyrosine, but they are known to form inflammatory mediators after conjugation with serum albumin. Our observations lead to the hypothesis that the serum level of advanced oxidized protein products is a prognostic marker of PD duration, and these oxidized proteins could participate in the development of parkinsonian neurodegeneration.