Patients with multiple sclerosis show increased oxidative stress markers and somatic telomere length shortening

Abstract

Lipid peroxidation due to oxidative stress (OS) may play an important role in the pathogenesis of chronic systemic inflammatory diseases such as multiple sclerosis (MS). Telomeres, repeated sequences that cap chromosome ends, undergo shortening with each cycle of cell division, resulting in cellular senescence. Research regarding telomere shortening has provided novel insight into the pathogenesis of various diseases. We hypothesized that OS damage leads to inflammatory reactions, which subsequently shortens the telomere length in MS. We enrolled 59 patients with MS, and age- and gender-matched 60 healthy controls. We divided MS subjects into three groups matched for age and gender according to the severity of disability: relatively benign course (BMS), secondary progressive MS, and primary progressive MS (PPMS). We analyzed the telomere length in peripheral blood mononuclear cells and the 8-iso-PGF2α concentration in urine, a reliable and stable marker of lipid peroxidation in vivo. The data showed significant higher levels of urinary 8-iso-PGF2α in MS subjects than in the controls. The lag-time, which represents the direct measurement of the resistance of low-density lipoprotein to oxidation, was shorter in the PPMS subjects than in the groups. Compared to that observed in the controls, the mean telomere length was significantly shorter in the PPMS group, whereas no significant telomere shortening was found between the controls and other subjects. Our data suggest that a decreased telomere length and enhanced lipid peroxidation reflects the severest stage of MS.

New Insights into the Role of Oxidative Stress Mechanisms in the Pathophysiology and Treatment of Multiple Sclerosis

“…The levels of thiobarbituric acid reactive substances and advanced glycation end-products can be assessed in saliva [73]. Urine may be a good material for the assessment of urinary 8-iso-PGF2 α , which is a marker of lipid peroxidation in vivo [81]. …”

“…Guan et al showed high levels of urinary 8-iso-PGF2 α (a marker of lipid peroxidation in vivo) in MS patients. The concentration of urinary 8-iso-PGF2 α was significantly higher in patients with SPMS and PPMS as compared to the control group [81]. It was also shown that a reduced level of prolyl oligopeptidase activity and activated α -2-macroglobulin level in the plasma were characteristic of PPMS and RRMS [51].…”

Decreased arylesterase activity of paraoxonase-1 (PON-1) might be a common denominator of neuroinflammatory and neurodegenerative diseases

“…Oxidative damage also appears to reflect in blood, saliva and urine (Karlík et al 2015;Guan et al 2015) and cerebrospinal fluid (CSF) of MS patients when compared with healthy controls (Mattsson et al 2007). …”

Physical Exercise Alleviates Health Defects, Symptoms, and Biomarkers in Schizophrenia Spectrum Disorder

“…Oxidative stress-mediated DNA damage is an important determinant of telomere shortening (e.g., Guan et al 2014;Nettle et al 2015). At critically shortened thresholds, genomic instability, replicative senescence, and apoptosis occur (Sampson et al 2006), with resultant chronic disorders (Friedrich et al 2000).…”