Protective effect of Eprosartan against ischemic acute renal injury: Acting on NF-κB, caspase 3, and Sirtuin 1.

Kidney ischemia/reperfusion (I/R) injury is a leading cause of acute kidney injury (AKI) occurring frequently under major surgeries and sepsis. This study aimed to evaluate the effect of Eprosartan, an angiotensin II receptor type-1 (AT-1) antagonist, on the kidney I/R rat model. Male Wistar rats (n = 24) were allocated into (i) Sham, (ii) Eprosartan, (iii) I/R, and (iv) Eprosartan + I/R groups. Animals in the last group received a single dose of Eprosartan (60 mg/kg) 1 h before kidney I/R. Renal oxidant/antioxidant, inflammatory (NF-κB p65, COX-2, IL-6, TNF-α), and apoptotic (caspase-3, Bax, Bcl2) factors along with Sirtuin 1, Klotho, and mitochondrial biogenesis (PGC-1α, and Sirtuin 3) factors were evaluated by Western blotting. Significant recovery of kidney function and increased levels of antioxidant markers were observed in the Eprosartan + I/R group. The Eprosartan anti-inflammatory activity was demonstrated by significant downregulation of NF-κB and its downstream pro-inflammatory factors. Eprosartan pretreatment could also abolish I/R-induced alterations in the apoptotic parameters. Moreover, Eprosartan + I/R rats significantly presented higher levels of Sirtuin 1 content. In conclusion, Eprosartan exhibited nephroprotective effects against kidney damage induced by I/R in rats by decreasing oxidative stress, inflammatory, and apoptotic pathways along with increasing Sirtuin1 level.