Protective effect of Eprosartan against ischemic acute renal injury: Acting on NF-?B, caspase 3, and Sirtuin

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-kappa B p65, COX-2, IL-6, TNF-alpha), and apoptotic (caspase-3, Bax, Bcl2) factors along with Sirtuin 1, Klotho, and mitochondrial biogenesis (PGC-1 alpha, 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-in-flammatory activity was demonstrated by significant downregulation of NF-kappa B and its downstream pro-inflammatory factors. Eprosartan pretreatment could also abolish I/R-induced alterations in the apoptotic pa-rameters. Moreover, Eprosartan + I/R rats significantly presented higher levels of Sirtuin 1 content. In conclu-sion, 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.

Automated summary

This study aimed to evaluate the effect of Eprosartan, an AT-1 antagonist, on kidney I/R injury in rats. Results showed that Eprosartan significantly improved kidney function and increased antioxidant markers. Eprosartan exhibited anti-inflammatory activity by downregulating NF-kappa B and pro-inflammatory factors. It also prevented I/R-induced changes in apoptotic parameters. Additionally, Eprosartan + I/R rats showed higher levels of Sirtuin 1. In conclusion, Eprosartan has nephroprotective effects against I/R-induced kidney damage in rats by reducing oxidative stress, inflammation, and apoptosis, as well as increasing Sirtuin 1 levels.