Influence of oxidant stress on clinical manifestations and quality of life in patients with generalized myasthenia gravis
Summary. The aim was to study the effect of oxidative stress indicators on the clinical manifestations of myasthenia gravis, as well as on the quality of life of patients. Materials and methods. The study included 147 patients with generalized myasthenia gravis (mean age 53.0 (37.0–65.0) years, 98 (66.7%) women and 49 (33.3%) men). 10 almost healthy individuals formed a control group to compare oxidative stress indicators. To quantify the clinical manifestations of myasthenia gravis, patients were assessed using the Qualitative Myasthenia Gravis Scale, and fatigue was assessed using the Fatigue Severity Scale. Quality of life was assessed using the Myasthenia Gravis Quality of Life-15 scale. The level of total protein, sulfhydryl groups, glutathione-dependent enzymes (glutathione peroxidase, glutathione reductase, glutathione-S-transferase), reduced and oxidized glutathione, heat shock protein with a mass of 70 kDa (HSP70) and nitrotyrosine as the main indicator of nitrosine stress were determined. For mathematical data processing, methods of parametric and nonparametric statistics were used. Results. The severe course of myasthenia gravis (according to the Qualitative Myasthenia Gravis Scale) had direct connections with nitrotyrosine and oxidized glutathione, while with other enzymes of the antioxidant system, mostly direct and strong correlations were determined (the higher the protein content, the higher the level of oxidative stress, the worse the condition of the patient with myasthenia). For the Qualitative Myasthenia Gravis Scale, the strongest association was determined with glutathione peroxidase (ρ=–0.78; p<0.001), for the Myasthenia Gravis — Activity of Daily Living Scale and the Fatigue Severity Scale — with glutathione reductase (ρ=–0.69 and ρ=–0.54 respectively; p<0.001), for the Myasthenia Gravis Quality of Life-15 scale — with sulfhydryl groups and glutathione reductase (both ρ=–0.62; p<0.001). Sulfhydryl groups had a strong direct correlation with reduced glutathione (r=0.83; p<0.001), and the reverse one with oxidized glutathione (r=–0.80; p<0.001). Strong feedback was determined between nitrotyrosine and reduced glutathione (r=–0.71; p<0.001), reduced and oxidized glutadione (r=–0.82; p<0.001). HSP70 correlates with both glutathione-dependent enzymes — glutathione peroxidase (r=0.63; p<0.001), glutathione reductase (r=0.68; p<0.001), glutathione-S-transferase (r=0.50; p<0.001), and with an indicator of nitrosine stress — nitrotyrosine (r=–0.64; p<0.001). In general, the coefficient of canonical correlation between the indicators of the clinical and neurological state of patients with myasthenia gravis and the complex of biochemical parameters associated with oxidative stress is R=0.85 (χ2=81.60; p<0.001). Conclusions. Indicators of oxidative stress affect the development of generalized myasthenia gravis and its severity, and also have an impact on the daily activity of patients, their level of fatigue, and quality of life indicators.
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