Background: In liver transplantation, up to 10% of early liver failures are attributed to ischemia and reperfusion (IR) injury, which is also associated with a higher incidence of acute and chronic rejection, thus increasing the need for re-transplantation. Drugs with anti-inflammatory, anti-fibrotic, and anti-proliferative effects, such as tamoxifen (TAM), may represent a promising therapeutic strategy. Therefore, the objective of this study was to evaluate the effects of tamoxifen on liver function in animals subjected to experimental hepatic ischemia and reperfusion.
Methods: Twenty-four male Wistar rats were divided into three groups: SHAM group (n=8), which did not undergo IR; IR group (n=8), subjected to hepatic ischemia (1 hour) and reperfusion (4 hours); and TAM group (n=8), pretreated with tamoxifen and subjected to the IR procedure. Partial hepatic ischemia (70%) was induced for 1 hour, followed by 4 hours of reperfusion. Tamoxifen was administered by gavage at a dose of 10 mg/kg in two doses: 24 hours before and 2 hours before hepatic IR. Serum levels of liver function markers (ALT, AST, GammaGT, and alkaline phosphatase) were assessed. Additionally, markers of renal function (serum creatinine and urea) were measured to evaluate systemic post-reperfusion stress. All the experiments were approved by institutional ethical committee.
Results: SHAM group animals showed normal levels of ALT, AST, GammaGT, and alkaline phosphatase (271±48 U/L, 203±83 U/L, 2.5±0.7 U/L, and 90±10 U/L, respectively). In contrast, IR group animals exhibited significant increases in these markers. However, TAM treatment substantially reduced these levels (ALT: 6651±1273 U/L vs. 543±44 U/L; AST: 4072±846 U/L vs. 271±100 U/L; GammaGT: 21±1 U/L vs. 5±0.5 U/L; alkaline phosphatase: 185±5 U/L vs. 90±6 U/L, respectively; p<0.05 for IR vs. TAM group). Regarding renal function, the SHAM group presented normal levels of serum creatinine and urea (0.59±0.02 mg/dL and 29±4 mg/dL, respectively). IR group animals showed elevated markers, while tamoxifen treatment significantly protected kidney function (serum creatinine: 1±0.03 vs. 0.54±0.04 mg/dL; urea: 48±2 vs. 32±3 mg/dL, respectively; p<0.05 for IR vs. TAM group).
Conclusions: Tamoxifen demonstrated significant hepatoprotective effects in this experimental model of hepatic ischemia and reperfusion, as evidenced by the marked reduction in serum liver enzyme levels. The drug also provided renal protection, suggesting systemic anti-inflammatory and protective actions. These findings support the potential of tamoxifen as a therapeutic agent to mitigate liver and kidney injury associated with ischemia and reperfusion, warranting further investigation in clinical contexts.