Increased levels of lipid hydroperoxides in plasma of patients with multiple sclerosis: a relationship with paraoxonase activity

Abstract

Paraoxonase, an enzyme associated with high density lipoproteins (HDL), plays an important role in the anti-oxidant and anti-inflammatory properties exerted by HDL. Increasing evidence supports a role of free radicals and oxidative stress in the inflammatory processes and in the pathogenesis of multiple sclerosis (MS). The aim of this study was to further investigate the relationship between oxidative damage and MS; therefore we compared the paraoxonase activity and levels of cholesteryl ester hydroperoxides (CE-OOH), as marker of lipid peroxidation, in plasma isolated from healthy subjects (n = 89) and from MS patients (n = 24) in the early stage disability (EDSS<3.5). Our results demonstrated for the first time that the activity of paraoxonase in the plasma of MS subjects was significantly lower with respect to controls (P <0.001). Moreover, our results showed a significant increase in the levels of CE-OOH in plasma from MS subjects (P<0.001). CE-OOH are biologically active substances derived from the oxidation of cholesteryl ester localized in the hydrophobic core of plasma lipoproteins (HDL, LDL). Therefore, our study demonstrates alterations of lipoprotein peroxidation in MS and provides further evidence that oxidative stress and impairment of the anti-oxidant system may play a role in MS.

Fumarates Promote Cytoprotection of Central Nervous System Cells against Oxidative Stress via the Nuclear Factor (Erythroid-Derived 2)-Like 2 Pathway

“…Targeting the Nrf2 pathway with small-molecule activators presents an attractive opportunity because the target is an intrinsic cellular pathway that is designed to be dynamically modulated. The need for this type of therapy in MS is clear, because current evidence indicates free radicals play a large role in MS pathogenesis (van Horssen et al, 2011), with damage to protein, lipid, and DNA in the tissues and cells proximal to lesion areas and in circulation (Vladimirova et al, 1998;Ferretti et al, 2005;van Horssen et al, 2008). It is noteworthy that these studies have shown that some antioxidant response proteins, including Nrf2, are elevated in MS lesions (van Horssen et al, 2008(van Horssen et al, , 2010; however, the degree of intrinsic antioxidant induction is apparently insufficient to ultimately prevent disease progression.…”

Nutrition in multiple sclerosis

“…It was prospective, case-control study among more than 7 million US military personnel, from which they recognized 257 patients with MS. Results showed that among whites risk for MS significantly decreased with In people with MS and animal models of MS, products such as peroxynitrite and superoxide are formed that are highly toxic to neurons (23)(24)(25). Vitamins A, C, and E, may decrease free radical induced cellular injury and this is the rationale for their use in MS (1).…”

Oxidative Stress and Neurotoxicity

“…However, there is growing awareness that disease progression in MS is associated with axonal degeneration, and accumulating data indicate that oxidative stress plays a major role in the pathogenesis of MS (281)(282)(283)(284). Increased levels of secondary products of oxidative stress and/or decreased levels of antioxidant enzymes and small molecule antioxidants are seen in blood and CSF during the active phases of MS (285)(286)(287)(288)(289).…”