Thymosin β4 Protects Against Hepatic Ischemia–Reperfusion Injury Through Multi-target Mechanisms

Objective: This study aimed to evaluate the hepatoprotective effects of thymosin β4 (Tβ4) administered at different time points (before ischemia and before reperfusion) in an experimental rat model of hepatic ischemia–reperfusion injury (HIRI). Methods: Thirty-two Sprague–Dawley rats were randomly divided into 4 experimental groups (n = 8 per group): C, IR, Tβ4/IR, and I/Tβ4/R. Ischemia was induced by occlusion of the infrarenal abdominal aorta for 90 minutes, followed by 180 minutes of reperfusion. Oxidative stress (PAB, FRAP, MDA, LOOH, SOD, GSH), inflammatory biomarkers (TNF-α, IL-6, IL-1β, NF-κB), apoptosis- and tissue injury–related biomarkers (caspase-9, MMP-9, hyaluronic acid, nitric oxide), serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, and histopathological changes were evaluated. Results: Hepatic IR significantly increased oxidative stress, lipid peroxidation, inflammatory cytokines, NF-κB activation, apoptosis-related and tissue injury–related biomarkers, nitric oxide, serum AST/ALT activities, and histopathological injury, while significantly reducing antioxidant capacity (all P < .05). Both Tβ4 treatment protocols attenuated these alterations, with improvements in oxidative stress-related parameters, inflammatory responses, apoptosis-related markers, tissue injury–related biomarkers, liver enzyme levels, and histopathological findings. Both Tβ4/IR and I/Tβ4/R groups showed improvements compared with the IR group. Conclusion: Thymosin β4 demonstrated hepatoprotective effects against HIRI, as evidenced by improvements in oxidative stress, inflammatory, apoptosis-related, biochemical and histopathological parameters. These findings support further investigation of Tβ4 as a potential hepatoprotective agent in experimental HIRI, including evaluation of different administration time points. Cite this article as: Işık M, Şahin G, Bolkent S, et al. Thymosin β4 protects against hepatic ischemia–reperfusion injury through multi-target mechanisms. Cerrahpaşa Med J 2026, 50, 0106, doi: 10.5152/cjm.2026.26106