Skeletal Muscle Ultrastructural Damage And Satellite Cell Responses Following Injury In GSHlow And GSHhigh Individuals

PURPOSE: To unravel the effect of glutathione (GSH) redox status on skeletal muscle ultrastructural damage and satellite cell responses following injury in individuals with different GSH levels. METHODS: 24 young men provided a resting biopsy of the vastus lateralis muscle and were clustered into a low or high group based on their intramuscular GSH content (GSHlow vs. GSHhigh group). Participants were supplemented with N-acetylcysteine (NAC) or placebo according to a crossover, double-blind design and underwent an exercise-induced muscle injury protocol of the quadriceps muscle. Skeletal muscle ultrastructural abnormalities and fiber type-specific satellite cell responses were assessed at baseline, as well as at 2- and 8-days post-injury (D-PI). RESULTS: In the GSHlow group, the GSH/GSSG ratio decreased at 2- and 8D-PI and was lower compared to the GSHhigh group (p < 0.05), with NAC mitigating this decline (p < 0.05). In the GSHhigh group, the GSH/GSSG ratio decreased at 2D-PI only in the placebo (p < 0.05). Z-line streaming increased at 8D-PI in both groups and trials (p < 0.05). Notably, NAC increased Z-line streaming in the GSHhigh group at 8D-PI (p < 0.05). Abnormal mitochondria increased in both groups and trials at 8D-PI (p < 0.05). Interestingly, NAC treatment increased the proportion of damaged mitochondria in the GSHhigh group at 8D-PI (p < 0.05). In the GSHlow group, type I- and II-associated Pax7+ cells increased at 2- and 8D-PI in both trials, but this effect was more pronounced under NAC treatment at 8D-PI (p < 0.05). In the GSHhigh group, Pax7+ cells increased at 2- and 8D-PI only in the placebo trial in both fiber types (p < 0.05). MyoD+ cells increased in the GSHlow group at 2D-PI in both trials and at 8D-PI only in the NAC trial in type II fibers (p < 0.05). In the GSHhigh group, MyoD+ cells in type I fibers increased only at 2D-PI in placebo, while MyoD+ cells in type II fibers increased in both trials at 2D-PI and only in placebo at 8D-PI (p < 0.05). CONCLUSION: Antioxidant treatment with NAC upregulates satellite cell responses in GSHlow individuals by recalibrating GSH redox status. However, in GSHhigh individuals, NAC treatment may result in increased ultrastructural abnormalities, indicating inhibition of the skeletal muscle regenerative process. Supported by: This research work was supported by the Hellenic Foundation for Research and Innovation (HFRI) under the HFRI PhD Fellowship grant (Fellowship number: 32) and the Postgraduate Program of Study “Exercise & Health: Testing & Prescription” of the Department of Physical Education and Sports Science, University of Thessaly, Greece.