gms | German Medical Science

Objectives: Trauma represents a major global cause of death, with severe trauma triggering an uncontrolled immune response that can harm distant organs, notably the liver, leading to organ failure. Approximately 5–10% of patients develop hepatic failure after experiencing hemorrhagic shock or polytrauma. Moreover, up to 50% of patients with multiple trauma are acutely intoxicated with alcohol upon admission, impacting immune responses. This study aimed to investigate the basic mechanisms of liver damage and inflammation following trauma hemorrhage and fracture (THFx), both with and without ethanol intoxication (EI). Additionally, the Wnt/b-catenin signaling pathway, known for its role in regeneration and immune cell adhesion was analyzed.

Methods: Twenty-four male C57BL/6J mice were randomly assigned to four experimental groups. Two hours post-surgery, 12 mice in each group received a gastric gavage of 0.9% NaCl or 35% EtOH, resulting in a blood alcohol concentration of 1.54 per mil at the time of surgery. Subsequently, seven animals per group underwent hemorrhagic shock with subsequent resuscitation followed by femoral osteotomy with external fixator (THFx) or sham procedures. Effects on the liver were evaluated 24 h post-surgery through immunohistology, gene expression analyses, and organ protein levels.

Results and conclusion: THFx induced liver damage, indicated by hematoxylin-eosin staining and increased caspase-3 positive cell numbers. Furthermore, it heightened liver inflammation, as indicated by increased polymorphonuclear leukocyte recruitment, elevated protein levels, and/or gene expression of inflammatory cytokines (CXCL1, IL-6, TNF-a, IL-1b, and CXCL2) in the tissue. EI alleviated the increased liver damage and inflammatory parameters in THFx mice, restoring them to the levels observed in sham animals. EI had no impact on sham animals concerning liver damage and inflammation. THFx significantly reduced E-cadherin and b-catenin levels in the cytosol and membrane, nearly abolishing their co-localization. EI prevented these effects. Additionally, EI increased the membrane and cytosolic co-localization of E-cadherin and b-catenin significantly in both sham and THFx goups.

THFx-induced liver injury in mice is accompanied by uncontrolled inflammation, a condition mitigated by EI. The reduction in the intracellular Wnt signaling protein b-catenin due to THFx suggests a potential decrease in liver regenerative capacity, which is counteracted by ethanol. Ethanol facilitates b-catenin stabilization through its interaction with E-cadherin, highlighting its role in fortifying liver integrity and responsiveness to potential stimuli activating Wnt signaling.