Empagliflozin alleviates hepatic ischemia-reperfusion injury by inhibiting c-Myc through the JAK1-STAT3 signaling pathway
Abstract
Hepatic ischemia-reperfusion injury (HIRI) is a critical factor affecting the outcomes of liver surgeries, with inflammation and apoptosis playing pivotal roles in its pathogenesis. Empagliflozin, an anti-diabetic drug, has demonstrated hepatoprotective effects in various liver diseases, but its role in HIRI remains unclear. This study aimed to explore the protective mechanisms of empagliflozin against HIRI. Using rat HIRI models and Transformed Human Liver Epithelial-2 (THLE-2), we employed immunohistochemistry, ELISA, qRT-PCR, and Western blot to evaluate the effects of empagliflozin. Results showed that empagliflozin pretreatment significantly alleviated HIRI by reducing apoptosis and suppressing the secretion of inflammatory mediators. Hypoxia/reoxygenation experiments further confirmed that empagliflozin inhibited apoptosis and inflammation in THLE-2 cells. Mechanistically, empagliflozin downregulated JAK1-STAT3 signaling pathway and the c-Myc, which are critical in HIRI progression. These findings reveal that empagliflozin mitigates HIRI by suppressing JAK1-STAT3 pathway and the c-Myc, thereby reducing inflammation and apoptosis. This study highlights empagliflozin's potential as a prophylactic agent for HIRI, offering a scientific basis for its clinical application in liver transplantation and other contexts requiring HIRI prevention. By demonstrating empagliflozin's ability to modulate key signaling pathways, our research provides new insights into therapeutic…
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