Intravenous hydrogen-rich acetated Ringer’s solution attenuates liver injury in heatstroke rats through endothelial glycocalyx preservation

Abstract

Abstract Heatstroke is a life-threatening systemic disorder characterized by hyperthermia, inflammatory activation, endothelial injury, and multiple organ dysfunction. The liver is particularly vulnerable, but effective post-onset therapeutic strategies remain limited. This study examined whether intravenous hydrogen-rich acetated Ringer’s solution (H-AR) attenuates liver injury after heatstroke onset in rats, in comparison with acetated Ringer’s solution alone (Control) and 2% hydrogen inhalation (HI). Liver injury was assessed 60 min after onset using histological scoring and liver enzyme measurements. Circulating markers of inflammation and endothelial injury, endothelial glycocalyx ultrastructure, and 24-h survival were also evaluated. Thermal exposure was comparable among the heatstroke groups. Both H-AR and HI significantly reduced histological liver injury scores compared with Control; H-AR showed significantly greater attenuation than HI and was the only intervention that significantly reduced alanine aminotransferase levels. Both hydrogen-based interventions suppressed high-mobility group box 1 and syndecan-1, preserved endothelial glycocalyx structure, and improved 24-h survival compared with Control. These findings suggest that post-onset intravenous H-AR attenuates heatstroke-associated liver injury, potentially through reduced inflammatory activation and endothelial glycocalyx preservation, and may offer advantages over hydrogen inhalation with respect to hepatoprotection.