Abstract
Enhancement of mitochondrial physiological function prevents sepsis-induced dysfunction. The present study aimed to elucidate the mechanism by which hydrogen (H(2)) affects mitochondrial function in a wild-type (WT) and homozygous nuclear factor erythroid 2-related factor 2 (Nrf2) knockout (KO, Nrf2(-/-)) murine model of sepsis. In myocardial tissues with severe sepsis, H(2) gas treatment reduced mitochondrial dysfunction, whereas zinc protoporphyrin (ZnPPIX) negated these beneficial effects. H(2) treatment upregulated the protein expression of mitofusin-2 (Mfn2), peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), and protein heme oxygenase-1 (HO-1) in WT mice with severe sepsis but not in their Nrf2(-/-) counterparts, and this upregulation was inhibited in the presence of ZnPPIX. In conclusion, the mechanism by which H(2) limits organ damage in mice with severe sepsis involves HO-1, whereas the mechanism that limits severe sepsis-related mitochondrial dysfunction involves both HO-1 and Nrf2.