Background: Hepatic ischemic reperfusion (I/R) injury is an inevitable critical problem occurs during resection of liver tumors, and liver transplantation. Silymarin is a herbal product widely used for its hepatoprotective effect. Gemfibrozil is a FDA-approved fibrate drug, commonly prescribed for management of dyslipidaemia.Objective: The aim of this work is to study the possible hepatoprotective effect of Silymarin, Gemfibrozil, and their combination against hepatic ischemic reperfusion injury in rats.

Materials & Methods: Rats were divided into six groups: Group1: normal control; Group2: sham-operated; Group3: I/R (Rats subjected to partial hepatic ischemia for 30 minute followed by 6 h reperfusion), Group4: Silymarin pretreated group (100 mg/kg orally once daily for 14 days); Group5: Gemfibrozil pretreated group (100 mg/kg orally once daily for 14 days), and Group 6: Silymarin and Gemfibrozil- pretreated group. Serum AST and ALT, hepatic tissue MDA, SOD, GSH-Px, TNF-α, MPO, caspase-3 levels, and real-time qPCR for gene expression of IκB-α, and PI3K, and its subunits (P85: p110 α /p110 β) were measured besides liver histopathology and 8-OHdG, NF-κB (p65), and caspase immunohistochemistry.

Results: I/R insult deteriorated the liver function and evoked oxidative stress, inflammation, and apoptosis. Pretreatment with Silymarin and /or Gemfibrozil improved the deteriorated liver function and the histopathological changes as well as attenuating oxidation, apoptosis and inflammatory processes.

Conclusion: The combination of Gemfibrozil and Silymarin has protective effects against liver I/R in rats better than each of these drugs alone due to antioxidant, anti-inflammatory and anti-apoptotic properties of the used drugs.