Antioxidant Defense Enzymes in Multiple Sclerosis: A 5-Year Follow-up Study.

Abstract

Oxidative stress biomarkers are increased in multiple sclerosis (MS) lesions. Antioxidant defense enzymes regulate reactive oxygen species that can cause tissue injury in MS. The study of 91 subjects included 64 relapsing-remitting MS (RR-MS, 72% female, baseline age 44.6±SD 11 years; disease duration: 13.3±8.8 years; median EDSS 2.0, IQR: 1.8) and 27 healthy controls (HC) subjects at baseline and 5-year follow-up (5YFU). Serum glutathione peroxidase (GPX), glutathione S-transferase (GST), glutathione reductase (GSHR), superoxide dismutase (SOD), and paraoxonase-1 (PON1) arylesterase and paraoxonase activities were measured using kinetic enzyme assays. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and an apolipoprotein (Apo) panel with ApoA-I, ApoA-II, ApoB, ApoC-II and ApoE were obtained. Serum neurofilament (sNfL) was used to assess axonal injury. Disability was measured on the Expanded Disability Status Scale (EDSS). GSHR activity was lower in HC compared to RR-MS at baseline and 5YFU. GPX (p=0.008) and PON-1 arylesterase and paraoxonase activities (both p=0.05) increased between baseline and 5YFU in HC but did not increase in RR-MS. At baseline and 5YFU, GPX and GST were associated with TC, LDL-C, and ApoA-II; GSHR was associated with ApoA-II and ApoC-II. Antioxidant enzymes were not associated with sNfL or EDSS in RR-MS. RR-MS patients did not exhibit the changes in antioxidant enzyme activities over 5YFU found in HC; however, the differences were modest. Antioxidant enzyme activities are not associated with disability.