Fimasartan ameliorates renal ischemia reperfusion injury via modulation of oxidative stress, inflammatory and apoptotic cascades in a rat model.

Ischemia-reperfusion injury (IRI) can be defined as changes in the functions and structures of the tissues resulting from the restoration of blood after a period of ischemia. This study aimed to assess the potential protective effect of Fimasartan (angiotensin receptor antagonist) in the bilateral renal IRI in male rats through its potential effect on renal functions, modulation of the inflammatory cascade, oxidative stress, and apoptotic effect. The animals were equally assigned into four groups. The sham (negative control) group was exposed to surgical conditions without induction of IRI. The control group was exposed to ischemia by occluding the renal pedicles by clamps for 30 min, followed by restoration of blood for 2h. The vehicle-treated group received dimethyl sulfoxide (DMSO) by intraperitoneal injection (IP) 30 minutes before clamping. Fimasartan-treated group: rats pretreated with Fimasartan a dose of 3 mg/kg IP; this was half hour before occluding the renal pedicles. Animals were then exposed to 30 min ischemia (clamping the renal pedicles) followed by 2h reperfusion by releasing the clamps. Blood samples were collected to examine the levels of serum urea and creatinine. Renal tissue was used to measure the levels of cytokines (TNFα, IL-6) and total antioxidant capacity (TAC). Immunohistochemistry was used to assess the levels of Bax, caspase 3, and Bcl-2. Histopathological analyses were performed to detect the parenchymal injury. The present study shows that pretreatment with Fimasartan improves kidney function through its effects on oxidative stress, cytokines, and apoptotic markers.

NEPHROPROTECTIVE EFFECT OF OLMESARTAN ON RENAL ISCHEMIA REPERFUSION INJURY IN MALE RATS: THE ROLE OF NRF2/HO-1 SIGNALING PATHWAY.

OBJECTIVE: The aim: To investigate the Nephroprotective potential of Olmesartan in RIRI via modulation of the Nrf2/OH-1 signaling pathway. PATIENTS AND METHODS: Materials and methods: Thirty male rats were equally divided into four groups. The sham group was exposed to surgical conditions without induction of RIRI. The control group was exposed to ischemia by clamping the renal pedicles for 30 min, followed by 2h of blood restoration. The vehicle-treated group was received dimethyl sulfoxide (DMSO) by intraperitoneal injection (IP) 30 min before clamping. RESULTS: Results: Olmesartan-treated group was pretreated with Olmesartan a dose of 10 mg/kg IP; 30 min prior to induction of ischemia. Following 30 min of ischemia, the clamps were released and allowed to the reperfusion for 2 h. Blood samples were collected to examine the levels of serum urea and creatinine. Kidney tissue was used to measure the levels of cytokines (TNFα, IL6, MCP, BAX, BCL2 and isoprostane F2. Immunohistochemistry was used to assess the levels of Nrf2 and HO-1. Histological analyses were used to detect the tubular damage in the kidney. CONCLUSION: Conclusions: The results showed that Olmesartan alleviates renal tissue damage through activating the antioxidant effect mediated by Nrf2 signaling.