Protective effects of treprostinil and ischemic preconditioning on hepatic ischemia-reperfusion injury and biomarkers in experimental studies in rats.

BACKGROUND: Hepatic ischemia-reperfusion injury (HIRI) remains one of the major causes of postoperative liver dysfunction following extensive hepatectomy and liver transplantation. Owing to its progressive and dynamic nature, HIRI may lead to multiple organ failure and a worsened outcome. Treprostinil is a relatively new synthetic prostacyclin analog with a potential beneficial effect against HIRI. Ischemic preconditioning (IP) is a promising method to protect against HIRI. AIM: To investigate HIRI biomarkers, their effects on liver and heart, and the effects of treprostinil and IP on these processes. METHODS: Forty male Wistar albino rats aged 3-4 months were randomly assigned to four groups of ten, subjected to a 3-hour surgical intervention, and then sacrificed. Hepatic ischemia was induced by clamping the hepatoduodenal ligament for 30 minutes, followed by reperfusion for 120 minutes. Treprostinil (100 ng/kg/minute for 24 hours) or IP before HIRI, no protection, and a sham operation were applied accordingly in each group. Liver and heart histopathology and specific serum and hepatic tissue biomarkers were assessed. RESULTS: HIRI deteriorated hepatocellular function and exacerbated liver and myocardial damage in the control group. Furthermore, HIRI triggered cytokine overexpression and protein carbonyl content (P < 0.001). Compared with those in the HIRI group, lower troponin I, tumor necrosis factor-α, endothelin-1, and interleukin-1β in serum and liver tissue were significantly correlated with reduced cellular necrosis and improved hepatocellular function in the treprostinil group (P < 0.001). Similar but less pronounced effects were observed in the IP group. Both treprostinil and IP had protective effects in hepatic and cardiac tissues. However, treprostinil showed slightly superior cardioprotective efficacy, as evidenced by a statistically significant difference in troponin I levels (P < 0.05) and histopathological scoring of myocardium samples, but there were no differences in the other parameters. CONCLUSION: HIRI results in oxidative stress and cytokine overexpression, which deteriorate hepatic function and accelerates myocardial damage. Treprostinil and IP are promising strategies for preventing reperfusion-induced cellular and systemic damage.