The Level of Isoprostanes as a Non-invasive Marker for in vivo Lipid Peroxidation in Secondary Progressive Multiple Sclerosis

Abstract

Oxidative stress leads to lipid peroxidation and may contribute to the pathogenesis of lesions in multiple sclerosis (MS), an autoimmune disease characterized by inflammatory as well as degenerative phenomena. Isoprostanes are prostaglandin-like compounds which are formed by free radical catalysed peroxidation of arachidonic acid esterified in membrane phospholipids. They are a new class of sensitive specific markers for in vivo lipid peroxidation. In this study 26 patients (15 females and 11 males; mean age 48.2 ± 15.2 year; mean disease duration 10.0 ± 6.5 year) with secondary progressive MS (SPMS) and 12 healthy controls were enrolled. In patients with multiple sclerosis the lipid peroxidation as the level of urine isoprostanes and the level of thiobarbituric acid reactive species (TBARS) in plasma were estimated. Moreover, we estimated the total antioxidative status (TAS) in plasma. It was found that the urine isoprostanes level was over 6-fold elevated in patients with SPMS than in control (P < 0.001). In SPMS patients TBARS level was also statistically higher than in controls (P < 0.01). However, we did not observed any difference of TAS level in serum between SPMS patients and controls (P > 0.05). In patients with SPMS the lipid peroxidation and oxidative stress measured as the increased level of isoprostanes was observed. Thus, we suggest that the level of isoprostanes may be used as non-invasive marker for a determination of oxidative stress what in turn, together with clinical symptoms, may determine an specific antioxidative therapy in SPMS patients.

Original article Evaluation of oxidative and nitrosative stress in relapsing remitting multiple sclerosis: effect of corticosteroid therapy

“…The source of isoprostanes may be oxidized arachidonic acid, derived not only from neuron membranes but also from membranes of different cells including erythrocytes. Furthermore, significantly reduced serum 8-epi-PGF2α levels in response to MP therapy indicate both the sensitivity and reliability of isoprostane measurement and the antioxidant protective effects of steroid treatment on membrane phospholipids in addition to their anti-inflammatory activity [4,8,17].…”

Redox regulation of cellular stress response in multiple sclerosis

“…There is evidence that MS is characterized not only by immune mediated inflammatory reactions but also by neurodegenerative processes [33,34]. A variety of studies, supporting a role for oxidative stress in MS, indicate that endogenous antioxidants are decreased in MS, and damage to mitochondria induced by lipid peroxidation can lead to further ROS generation [35][36][37][38][39]. However, up-regulation of antioxidants in astrocytes and macrophages in active MS lesions [30] as well as in leukocytes suggests that endogenous protection from oxidative damage could limit the deleterious consequences of the oxidative stress per se [40].…”

Original article Suppression of the lipid peroxidation process in the CNS reduces neurological expression of experimentally induced autoimmune encephalomyelitis

“…Free radi cal catalyzed peroxidation of the arachidonic acid, ester ified in membrane phospholipids, transform it into pro staglandinlike, but cyclooxygenase-independent, isoprostanes. On the other hand, docosahexanoic acid (DHA) forms neuroprostanes, which are found also in the normal brain tissue, regulating its other (non-neuronal) biological effects [20].…”