AMPK activation mediates the antioxidant and anti-inflammatory effects of oleuropein in renal ischemia–reperfusion injury

Résumé

In the present study, we investigated the protective effect of OLE in a renal ischemia/reperfusion (I/R) rat model. We assessed whether OLE action depends on the modulation of AMPK-mediated oxidative stress and inflammation pathways. Rats were subjected to 60-min of renal ischemia followed by 120-min of reperfusion. OLE (50 mg/kg, per os) was administered for three consecutive days before I/R. Ara-A, an AMPK inhibitor, was infused at a rate of 100 μg/kg per min for 10 min before the onset of ischemia. Our results showed that OLE treatment improved significantly renal function, cell integrity and antioxidant status. These effects were completely blunted after Ara-A administration. Rats’ pretreatment with OLE reduced NF-κB pathway through the phosphorylation of AMPK and its downstream target molecule COX 2, an effect that was abolished following AMPK inhibition. In conclusion, this study reveals that OLE pretreatment attenuates kidney injury after I/R and this beneficial effect is related to the activation of AMPK pathway. These results emphasize oleuropein therapeutic potential for limiting oxidative and inflammatory damages associated with renal I/R.