Effects of Palmitoylethanolamide and Silymarin Combination Therapy in an Animal Model of Kidney Ischemia and Reperfusion

Silymarin, a poliphenolic compound, has multiple pharmacological activities including antioxidant and anti‐inflammatory effects. Palmitoylethanolamide (PEA) has been extensively studied and its capability to reduce inflammatory processes and ischemia/reperfusion (I/R) damage in various organs is well established. The aim of this study was to investigate the efficacy and safety of silymarin combination with PEA in a mouse model of renal I/R. Mice were subjected to bilateral renal artery occlusion (30 min) and reperfusion (6 h) and received intraperitoneally silymarin (100, 30 and 10 mg/kg); PEA (1 mg/kg); PEA (1mg/kg)+ silymarin (10mg/kg) as a combination therapy 15 min before release of clamps. The treatment with silymarin reduced kidney dysfunction, histological damage, neutrophil infiltration and oxidative stress in a dose dependent manner. Furthermore, PEA +silymarin combination therapy showed a significant synergistic effect. Therefore, NF‐κB and apoptosis pathways were also significantly inhibited. Our results clearly demonstrate that PEA+silymarin combination therapy significantly attenuated the degree of renal inflammation.