8-epi-prostaglandin-f2alpha and Multiple-Sclerosis

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.

Topics: Adult; Dinoprost; Female; Humans; Leukocytes, Mononuclear; Lipid Peroxidation; Male; Middle Aged; Multiple Sclerosis; Oxidative Stress; Telomere Shortening

The CSF level of the isoprostane 8-epi-prostaglandin (PG)-F2alpha (a reliable marker of oxidative stress in vivo) was three times higher in subjects with definite MS than in a benchmark group of subjects with other neurologic diseases. This increase was not correlated with that of PGE2 levels, measured as an index of cyclooxygenase activity, and was much lower in steroid-treated patients. The levels of 8-epi-PGF2alpha were moderately correlated with the degree of disability.

Topics: Adult; Aged; Dinoprost; Dinoprostone; Disabled Persons; F2-Isoprostanes; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Osmolar Concentration; Oxidative Stress; Prostaglandin-Endoperoxide Synthases; Reference Values