Protective effect of dapagliflozin against hepatic ischemia-reperfusion injury in rats

Hepatic ischemia-reperfusion (IR) injury is a complex pathophysiological process that frequently complicates major hepatobiliary surgeries requiring vascular inflow occlusion, thereby presenting a critical clinical challenge. The present study aimed to investigate the prophylactic efficacy of dapagliflozin (Dapa), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, against oxidative stress, inflammation, apoptosis, and histopathological damage in a rat model of total hepatic IR.

A total of forty male Sprague Dawley rats were randomly assigned into four groups: Sham, IR, Dapa1 + IR (1 mg/kg), and Dapa10 + IR (10 mg/kg). Dapa was administered orally to the treatment groups for five consecutive days prior to the induction of ischemia. The IR model was induced via 30 min of total hepatic ischemia followed by 2 h of reperfusion. Hepatic injury was assessed by evaluating plasma ALT and AST levels, tissue oxidative stress parameters (MDA, GSH, SOD, and CAT), inflammatory markers (NF-κB, TNF-α, IL-1β), Caspase-3 levels, and histopathological changes. Compared with the Sham group, the IR group exhibited significantly elevated liver enzyme levels, increased lipid peroxidation, and depleted antioxidant capacity. Furthermore, the IR group demonstrated marked elevations in pro-inflammatory cytokines and Caspase-3 levels, along with severe histopathological damage. Conversely, Dapa pretreatment preserved liver function, attenuated oxidative stress, and restricted both the inflammatory response and apoptosis in a dose-dependent manner.

Dapa effectively protects liver tissue against IR injury through its antioxidant and anti-inflammatory properties, highlighting its potential as a prophylactic agent for hepatic IR injury.