Glutathione alleviates acute intracerebral hemorrhage injury via reversing mitochondrial dysfunction.

Glutathione (GSH) has been studied for its neuroprotection value in several diseases, but the effect of GSH on intracerebral hemorrhage (ICH) is unclear. In this study, we examined the protective effects of GSH in an experimentally induced ICH model and investigated the relative mechanisms. Adult male C57BL/6j mice were randomized into Sham, ICH and GSH treatment groups. GSH was injected with the dose of 50, 100 or 200 mg/kg once per day for 3 days, starting immediately after operation. The results revealed a GSH-mediated improvement of neurological deficits score (NDS), motor and sensory functions impairment in a dose-dependent manner three days post ICH (p < 0.01, GSH 200 vs ICH. Sham, n = 12; ICH, n = 9; GSH 50, n = 10; GSH 100, n = 10; GSH 200, n = 11) in addition to significantly reduced mortality rate (p = 0.2632, GSH 200 vs ICH. n = 12 per group) and damage volume (p < 0.05, GSH 200 vs ICH. n = 12 per group). GSH treatment also attenuated injury measured by decreased brain edema (p < 0.05, GSH 200 vs ICH. Sham, n = 10; ICH, n = 10; GSH 200, n = 12), blood-brain barrier disruption (p < 0.05, GSH 200 vs ICH. Sham, n = 10; ICH, n = 10; GSH 200, n = 12), and histopathological damage (p < 0.05, GSH 200 vs ICH. Sham, n = 6; ICH, n = 6; GSH 200, n = 8) 72 h after ICH. In addition, GSH treatment also decreased cell apoptosis (p < 0.01, GSH 200 vs ICH. Sham, n = 6; ICH, n = 6; GSH 200, n = 8) and resulted in up-regulated protein expression of complex I (p < 0.01, GSH 200 vs ICH. Sham, n = 6; ICH, n = 6; GSH 200, n = 8), which was consistent with an overall up-regulation of complex I function in mitochondria using Oxygraph-2 K high resolution respirometry (p < 0.05, GSH 200 vs ICH. Sham, n = 4; ICH, n = 5; GSH 200, n = 6). In conclusion, GSH effectively improved the prognosis of ICH mice by attenuating neurological impairment, decreasing neural damage, and inhibiting apoptosis. The neuroprotection by GSH resulted from the up-regulation of mitochondrial oxidative respiration function. The results of our study suggest that GSH can be a potential therapeutic agent for ICH.