Immunopharmacology and inflammationEffects of palmitoylethanolamide and silymarin combination treatment in an animal model of kidney ischemia and reperfusion

The aim of this study was to investigate the efficacy of PEA+silymarin as a combination treatment in a mouse model of renal I/R and to verify whether PEA+silymarin could exert more potent effects compared to the single substances even if administered at lower doses. Mice were subjected to bilateral renal artery occlusion (30 min) and reperfusion (6 h) and received intraperitoneally silymarin (100, 30 and 10 mg/kg) or PEA (1 mg/kg) or PEA (1 mg/kg)+silymarin (10 mg/kg) 15 min before release of clamps. Specific indicators of renal dysfunction, tubular injury, myeloperoxidase activity and malondialdehyde levels were measured. The nuclear factor κB pathway and apoptotic mechanisms were also investigated. The treatment with silymarin reduced kidney dysfunction, histological damage, neutrophil infiltration and oxidative stress in a dose dependent manner. Furthermore, PEA+silymarin showed a significant potentiated effect. Therefore, NF-κB and apoptosis pathways were also significantly inhibited. Our results clearly demonstrate that PEA+silymarin treatment attenuated the degree of renal inflammation.