Trentini Alessandro, Castellazzi Massimiliano, Romani Arianna, Squerzanti Monica, Baldi Eleonora, Caniatti Maria Luisa, Pugliatti Maura, Granieri Enrico, Fainardi Enrico, Bellini Tiziana, Cervellati Carlo
Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy.
Neurology Unit, Department of Neurosciences and Rehabilitation, Azienda Ospedaliera-Universitaria, Arcispedale S. Anna, 44124 Ferrara, Italy.
J Neurol Sci. 2017 Jun 15;377:133-136. doi: 10.1016/j.jns.2017.04.021. Epub 2017 Apr 13.
Multiple sclerosis (MS) patients have increased brain iron deposition with higher oxidative stress (OxS). These two features can be caused by an inefficient removal of free iron from extracellular compartment. Ferroxidase activity (Feox) exerted by ceruloplasmin (FeoxCp) and by other molecules (FeoxII) appears to have a central role in this process. The aim of this study was to investigate serum and cerebrospinal fluid (CSF) total Feox, FeoxII and FeoxCp activities in MS patients and neurological controls. Serum and CSF Feox activity, FeoxII and FeoxCp activity was measured in 91 relapsing-remitting (RR) MS patients, 79 subjects with other inflammatory neurological disorders (OIND) and 65 with non-inflammatory neurological disorders (NIND), as controls. This study was approved by the Local Committee for Medical Ethics in Research. Serum total Feox activity was lower in MS group than in both NIND and OIND, with only the former control group differing significantly (p<0.001); FeoxII and FeoxCp activities were comparable among the groups. Serum Feox activities were not associated with disease activity as assessed by clinical examination or by Magnetic Resonance Imaging (MRI). Only total Feox activity was detectable in the CSF and was not different in MS compared to either OIND or NIND. In conclusion, a condition of low systemic Feox may increase the susceptibility of MS patients to iron(II) mediated-oxidative damage. This alteration is not reflected in CSF, suggesting that agents endowed with Feox activity might have different impact in iron homeostasis in the central nervous system compared to periphery.
多发性硬化症（MS）患者脑铁沉积增加，氧化应激（OxS）水平更高。这两个特征可能是由于细胞外间隙游离铁清除效率低下所致。铜蓝蛋白（FeoxCp）和其他分子（FeoxII）发挥的亚铁氧化酶活性（Feox）似乎在这一过程中起核心作用。本研究的目的是调查MS患者以及神经疾病对照者血清和脑脊液（CSF）中的总Feox、FeoxII和FeoxCp活性。对91例复发缓解型（RR）MS患者、79例患有其他炎性神经疾病（OIND）的受试者和65例患有非炎性神经疾病（NIND）的受试者作为对照，测量其血清和脑脊液中的Feox活性、FeoxII和FeoxCp活性。本研究获得了当地医学伦理研究委员会的批准。MS组血清总Feox活性低于NIND组和OIND组，仅前一个对照组有显著差异（p<0.001）；FeoxII和FeoxCp活性在各组之间相当。血清Feox活性与通过临床检查或磁共振成像（MRI）评估的疾病活动度无关。脑脊液中仅可检测到总Feox活性，MS组与OIND组或NIND组相比无差异。总之，全身性低Feox状态可能会增加MS患者对铁（II）介导的氧化损伤的易感性。这种改变在脑脊液中未体现，这表明具有Feox活性的物质对中枢神经系统铁稳态的影响可能与外周不同。
