Hydrogen Sulfide Ameliorates Sepsis-Induced Brain Injury in Athletes by Upregulating HO-1 to Inhibit HMGB1 Release: Implications for Sports Medicine
Keywords:
Sepsis, Hydrogen sulfide, Heme oxygenase-1,Cognitive function, High-mobility group box 1Abstract
Objective: This study investigates the protective effects of hydrogen sulfide (H2S) on sepsis-induced brain injury, particularly in the context of athletes, focusing on the modulation of HO-1 and its potential to inhibit HMGB1 release.
Methods: Male ICR mice underwent cecal ligation and puncture (CLP) to induce sepsis. H2S was administered immediately prior to and at 1 and 12 hours post-operation. The HO-1 inhibitor, Zinc protoporphyrin IX (ZnPPIX), was injected intraperitoneally one hour before surgery. Survival rates were monitored over 7 days. Cognitive functions were assessed using the Morris water maze and Y-maze tests. Neuronal apoptosis in the hippocampus was evaluated through TUNEL assay, while protein and mRNA levels of HO-1 and HMGB1, as well as HO-1 activity, were measured in hippocampal neurons.
Results: Treatment with H2S significantly improved survival rates and cognitive outcomes in septic mice, indicating a protective effect against brain injury. Pathological damage and alterations in apoptotic markers (Bad and Bcl-2) in the hippocampus were substantially reduced. The beneficial effects of H2S were attributed to a reduction in HMGB1 levels and enhanced expression and activity of HO-1 in the hippocampus.
Conclusion: H2S treatment may offer a viable therapeutic strategy to mitigate sepsis-induced brain injury by enhancing HO-1 activity and reducing HMGB1 release. This approach holds particular promise for athletes recovering from sepsis, aiming to minimize neurological impact and expedite return to performance. Further investigation in athlete-specific models is recommended to fully understand the implications for sports medicine.