Renoprotective effect of aliskiren on renal ischemia/reperfusion injury in rats: electron microscopy and molecular study

Abstract

(2015) Renoprotective effect of aliskiren on renal ischemia/reperfusion injury in rats: electron microscopy and molecular study, Renal Failure, 37:2,[343][344][345][346][347][348][349][350][351][352][353][354] Purpose: To determine the protective effect of aliskiren on ischemia-reperfusion (I/R) injury in a rat renal (I/R) model. Methods: Rats were randomly divided into five groups: sham control group; sham control with aliskiren pretreatment; I/R group and I/R with two doses of aliskiren pretreatment. Rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. Aliskiren (50 and 100 mg/kg) was administered orally by gavage 24 and 1 h prior to ischemia. After 24 h reperfusion, kidney samples were taken for the determination of malondialdehyde (MDA) level, superoxide dismutase (SOD), glutathione (GSH) activity and histological evaluation. The level of serum creatinine (SCR) and blood urea nitrogen (BUN), renin and angiotensin II (AT-2) was measured in serum samples. Results: Kidneys from I/R groups showed significant increase in MDA level and significant decrease in GSH, and SOD activity. IL-1b, iNOS and NFkB gene expression significantly increased in the I/R groups in the rat kidney tissue. Aliskiren treatment showed a significant down-regulatory effect on IL-1b, iNOS and NFkB mRNA expression. Compared with the sham group, SCR and BUN, renin and AT-2 were significantly increased in the I/R rats, accompanied by histopathological damage to the kidney. Conclusion: Pretreatment with aliskiren ameliorated I/R-induced renal injury through decreasing nitric oxide and AT-2 levels and by the reduction of injury induced by I/R injury and ameliorated renal histopathological molecular and biochemical changes.

The Role of RAAS Inhibition by Aliskiren on Paracetamol-Induced Hepatotoxicity Model in Rats

“…Therefore, the suppression of the RAAS with aliskiren in the paracetamol‐induced hepatotoxicity group could reduce the oxidative stress‐induced damage. Earlier studies performed with captopril and aliskiren showed that inhibition of Ang II reduced the production of free oxygen radicals [He et al, ; Ziypak et al, ]. Our previous studies showed that aliskiren protects against oxidative stress [Akpinar et al, ; Ziypak et al, ], which is consistent with our results on paracetamol toxicity.…”

“…Our results also support these findings. Furthermore, aliskiren treatment increases the SOD activity of kidneys in renal ischemia/reperfusion injury showing high antioxidant properties [Ziypak et al, ]. Similar to this study, aliskiren treatment increased SOD activity in low dose.…”

“…Blazka et al indicated that increased TNF‐α production leads to hepatic damage secondarily in addition to hepatic damage of metabolites [Blazka et al, ]. In addition, increased Ang II levels were shown to aggravate oxidative stress and inflammation in previous studies [Kim et al, ; Ziypak et al, ]. In our study, the TNF‐α levels that were increased in paracetamol toxicity and decreased in the aliskiren treatment group may be due to the inhibition of Ang II production, or the previously shown antioxidant or anti‐inflammatory effects of aliskiren.…”

“…In a Karakus et al study, GSH levels were decreased in the paracetamol‐induced hepatotoxicity group and treatment with agomelatin decreased GSH levels [Karakus et al, ]. Further aliskiren increased GSH levels in a study performed on kidney tissue [Ziypak et al, ]. Similarly, both doses of aliskiren treatment increased the GSH levels that had been compromised by the paracetamol toxicity.…”

“…Aliskiren has a positive effect on inflammatory cytokines [Aihara et al, ; Ziypak et al, ] and oxidant/antioxidant balance [Ziypak et al, ]; as a result, it is thought to be used in the treatment of many diseases experimentally. Aliskiren may lower the production of Ang II during the process of chronic liver injury and concomitantly ameliorate inflammation and fibrosis.…”