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

Abstract

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.

Moexipril Improves Renal Ischemia/Reperfusion Injury in Adult Male Rats

“…This finding was also reported in other research who found that rats exposed to renal ischemia reperfusion by occluding the renal pedicles for 30 min and restoring blood for 2h had higher caspase 3 and lower Bcl2 levels than the sham group. 26 Moexipril pretreatment group had a substantial reduction in caspase-3 kidney level and increased Bcl-2 compared to induced group (Figures 7 and 8). Thus, moexipril has antiapoptotic effects, although there is no previous study on Bcl-2 or caspase-3 in RIRI models.…”

Reducing Oxygen Demand to Alleviate Acute Kidney Injury

“…Not surprisingly, angiotensin II increases oxygen consumption by renal mitochondria [134]. While angiotensin receptor blockers (ARBs) have repeatedly shown benefits in animal models of AKI [135][136][137][138] and CKD in humans [139][140][141], the results from clinical trials of AKI with ARBs and angiotensin converting enzyme inhibitors (ACEIs) have had mixed results (Table 1). One potential adverse impact of ACEIs and ARBs in the setting of AKI is that they could worsen renal hypoperfusion.…”

Evaluation of the efficacy of rat renal ischemia-reperfusion injury after itaconic acid and its isomers treatment by contrast-enhanced ultrasound(CEUS)

“…Current studies have proposed dialysis treatment [23], alternative therapy [24], stem cell therapy [25][26][27], etc., but these treatments all have certain limitations. Based on this, more and more research is targeting the drug treatment of AKI [28][29][30].…”