No abstract

Oxidative status may play a role in chronic inflammation and neurodegeneration which are considered critical etiopathogenetic factors in Multiple Sclerosis (MS), both in the early phase of the disease and in the progressive one. The aim of this study is to explore oxidative status related to iron metabolism in peripheral blood of stable Relapsing-Remitting MS with low disability. We studied 60 Relapsing-Remitting MS patients (age 37.2 ± 9.06, EDSS median 1.0), and 40 healthy controls (age 40.3 ± 10.86). We measured total hydroperoxides (dROMs test) and Total Antioxidant Status (TAS), along with the iron metabolism biomarkers: Iron (Fe), ferritin (Ferr), transferrin (Tf), transferrin saturation (Tfsat), and ceruloplasmin (Cp) panel biomarkers [concentration (iCp) and enzymatic activity (eCp), copper (Cu), ceruloplasmin specific activity (eCp:iCp), copper to ceruloplasmin ratio (Cu:Cp), non-ceruloplasmin copper (nCp-Cu)]. We computed also the Cp:Tf ratio as an index of oxidative stress related to iron metabolism. We found lower TAS levels in MS patients than in healthy controls (CTRL) and normal reference level and higher dROMs and Cp:Tf ratio in MS than in healthy controls. Cp and Cu were higher in MS while biomarkers of iron metabolism were not different between patients and controls. Both in controls and MS, dROMs correlated with iCp (CTRL r = 0.821, p < 0.001; MS r = 0.775 p < 0.001) and eCp (CTRL r = 0.734, p < 0.001; MS r = 0.820 p < 0.001). Moreover, only in MS group iCp correlated negatively with Tfsat (r = -0.257, p = 0.047). Dividing MS patients in “untreated” group and “treated” group, we found a significant difference in Fe values [F(2, 97) = 10.136, p < 0.001]; in particular “MS untreated” showed higher mean values (mean = 114.5, SD = 39.37 μg/dL) than CTRL (mean 78.6, SD = 27.55 μg/dL p = 0.001) and “MS treated” (mean = 72.4, SD = 38.08 μg/dL; p < 0.001). Moreover, “MS untreated” showed significantly higher values of Cp:Tf (mean = 10.19, SD = 1.77∗10-2; p = 0.015), than CTRL (mean = 9.03, SD = 1.46 ∗10-2). These results suggest that chronic oxidative stress is relevant also in the remitting phase of the disease in patients with low disability and short disease duration. Therefore, treatment with antioxidants may be beneficial also in the early stage of the disease to preserve neuronal reserve.

No abstract

Two single nucleotide polymorphisms in Cu-transporter ATP7B alter protein properties and copper status in humans.

Trace metal dyshomeostasis has been linked to loss of cognitive performance. In particular, a disturbance in the regulation of copper (Cu), characterized by an increase in circulating Cu not bound to ceruloplasmin (non-Cp Cu), is thought to play a role in the development of Alzheimer disease (AD) and other neurodegenerative diseases in the aging population. Non-Cp Cu is redox active and its toxicity is thought to result from its ability to accelerate oxidative stress and advanced glycation endproduct (AGE) formation, leading to extracellular matrix damage in tissues including the brain. Cognitive loss is increasingly recognized to be a feature of type 2 diabetes and the increased AGE formation characteristic of diabetes may play a role in the development of this complication. There also is evidence for copper dyshomeostasis in type 2 diabetes, and therefore this could contribute to the cognitive deterioration associated with this disease. Demonstrating that disturbances of copper homeostasis correlate with an increased rate of cognitive decline in type 2 diabetes patients, and that they correlate with an increased rate of conversion from prediabetes to diabetes would bring almost immediate benefits in the clinical community in terms of treatment efficacy, AD prevention, and cost savings.