Background and objectives: Ischemia–reperfusion (IR) caused by infrarenal abdominal aorta cross-clamping is an important factor in the development of ischemia–reperfusion injury in various distant organs. Materials and Methods: We investigated potential antioxidant/anti-inflammatory effects of thymosin beta 4 (Tβ4) in a rat model of abdominal aortic surgery-induced IR. Tβ4 (10 mg/kg, intravenous (i.v.)) was administered to rats with IR (90-min ischemia, 180-min reperfusion) at two different periods. One group received Tβ4 1 h before ischemia, and the other received 15 min before the reperfusion period. Results: Results were compared to control and non-Tβ4-treated rats with IR. Serum, bronchoalveolar lavage fluid and lung tissue levels of oxidant parameters were higher, while antioxidant levels were lower in the IR group compared to control. IR also increased inflammatory cytokine levels. Tβ4 reverted these parameters in both Tβ4-treated groups compared to the untreated IR group. Conclusions: Since there is no statistical difference between the prescribed results of both Tβ4-treated groups, our study demonstrates that Tβ4 reduced lung oxidative stress and inflammation following IR and prevented lung tissue injury regardless of timing of administration.

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

Hepatic ischemia–reperfusion injury is a major clinical problem associated with liver surgery, trauma, and transplantation, characterized by oxidative stress, inflammation, microcirculatory dysfunction, and apoptosis. Fluoxetine, a selective serotonin reuptake inhibitor, has been reported to exert antioxidant, anti-inflammatory, and antiapoptotic effects. The present study aimed to investigate the potential protective effects of fluoxetine against experimental hepatic ischemia–reperfusion injury in rats. Male Wistar rats were randomly assigned to three groups: control, ischemia–reperfusion and fluoxetine-treated ischemia–reperfusion ( n = 7 each). Hepatic ischemia–reperfusion injury was induced by infrarenal abdominal aortic cross-clamping for 60 min followed by 120 min of reperfusion. Fluoxetine (20 mg/kg/day, intraperitoneal) was administered for three consecutive days prior to ischemia. Oxidative stress markers, antioxidant parameters, inflammatory and anti-inflammatory cytokines, apoptotic markers, and specific tissue injury biomarkers were measured in liver homogenates using ELISA. Histopathological alterations were evaluated by light microscopy. Ischemia–reperfusion significantly increased oxidant markers, inflammatory cytokines, NF-κB activation, apoptotic indices, liver enzyme levels, and histological damage, while reducing antioxidant capacity. Fluoxetine treatment markedly restored antioxidant defenses, suppressed oxidative stress, inflammation, apoptosis, and microcirculatory injury, and significantly improved histopathological findings compared with the untreated ischemia–reperfusion group. Fluoxetine exerts a protective effect against hepatic ischemia–reperfusion injury through antioxidant, anti-inflammatory and antiapoptotic mechanisms, suggesting its potential as a therapeutic agent in conditions associated with hepatic ischemia–reperfusion.