Inhalation of 4% and 67% hydrogen ameliorates oxidative stress, inflammation, apoptosis, and necroptosis in a rat model of glycerol-induced acute kidney injury

Acute kidney injury (AKI) is the major complication of rhabdomyolysis (RM) clinically, which is usually mimicked by glycerol injection in basic research. Oxidative stress, inflammatory response and apoptosis are recognized to play important roles in development of this disease. Recently, numerous studies have reported the therapeutic effects of molecular hydrogen (H(2)) on oxidative stress and inflammation-related diseases. Here, the effects of H(2) against glycerol-induced AKI and the underlying mechanisms were explored in rats. Low (4%) and high (67%) concentrations of H(2) were prepared using a self-made device to investigate the dose-response. After 72 hours of glycerol injection (8 mL/kg), we found that glycerol triggered oxidative stress, inflammatory reactions, and apoptotic events. These caused subsequent renal damage, evidenced by a significant reduction of antioxidases and up-regulation of the relevant damaged biomarkers. H(2) inhalation reversed the above alterations and exerted renoprotective effects. Interestingly, for RM/AKI-related factors, no consistent dose-response benefits of H(2) were observed. However, higher concentration of H(2) inhalation improved histological and morphological changes better. This study suggests that H(2) is a potential alternative therapy to prevent or minimize RM induced AKI possibly via its antioxidant, anti-inflammatory, anti-apoptotic and anti-necroptotic properties.