Exogenous H2S suppresses traumatic stress-induced changes of HMGB1 and ERS in rat liver and lungs.

OBJECTIVES

Traumatic stress triggers systemic inflammation and organ injury via HMGB1 and endoplasmic reticulum stress (ERS), but whether H2S modulates this pathway remains unclear. This study aimed to investigate the effects of exogenous H2S (NaHS, an H2S donor) on traumatic stress-induced HMGB1 and ERS changes in rat liver and lungs.

METHODS

Male SD rats underwent bilateral hindlimb crush. Sixty rats were assigned to sham, crush, NaHS pretreatment (14, 28, 56 μmol/kg), delayed NaHS (120 μmol/kg), and NaHS-only groups (n=6). Serum ALT/AST, histopathology, HMGB1 (ELISA/IHC), and ERS markers (GRP78, caspase-12, CHOP, IRE1α) were assessed.

RESULTS

Crush increased ALT/AST, liver/lung injury, plasma HMGB1, cytoplasmic HMGB1 translocation, and ERS activation. NaHS at 28 μmol/kg offered strongest protection, reducing all parameters. The 14 μmol/kg dose had limited effect; 56 μmol/kg showed reduced efficacy and mild toxicity. Delayed 120 μmol/kg also attenuated injury and HMGB1-ERS activation, though less effectively than 28 μmol/kg pretreatment.

CONCLUSIONS

Exogenous H2S attenuates traumatic stress-induced acute liver/lung injury, likely by inhibiting the HMGB1-mediated ERS pathway. Optimal protection occurs at 28 μmol/kg, while higher doses exhibit biphasic effects. These findings may inform forensic and critical care strategies.