Glutathione imbalance in blood of patients with Duchenne muscular dystrophy

Oxidative stress may contribute to muscle degeneration in Duchenne muscular dystrophy (DMD) and may influence the disease progression and severity. In the past few years antioxidant drugs have been proposed as potential therapeutic strategy for DMD and several clinical trials with different compounds are ongoing. Glutathione is the main nonprotein antioxidant in cells, mostly occurring in its reduced form (GSH) that can be oxidized to GSSG under oxidative stress. The GSH/GSSG ratio is critical and must be balanced, with GSH exceeding 100/1 the GSSG. Glutathione is a highly sensitive redox indicator and represents a non-invasive and reliable systemic biomarker also in monitoring clinical trials. The objective of the study is to assess the plasma levels of total, reduced, oxidized and protein-bound glutathione and the glutathione-related antioxidant enzyme activities, plasma thiols and carbonyl content in DMD patients. The results are that we analyzed GSH and GSSG levels in whole blood of 12 DMD patients. Blood GSH concentration was consistently decreased in DMD patients with respect to the controls (p < 0.001), whereas its oxidized form (GSSG) was significantly increased (p < 0.0001). Accordingly, plasma thiols and glutathione peroxidase enzyme, which requires GSH as a co-substrate for its detoxifying activity, were further decreased in patients. These results strongly support the involvement of the oxidative stress in the downstream cascade to dystrophic pathology and indicate glutathione as an efficient systemic redox biomarker. Blood GSH and GSSH should be considered and validated as surrogate non-invasive biomarkers to test the efficacy of antioxidant treatments.