Atorvastatin treatment attenuates renal injury in an experimental model of ischemia–reperfusion in rats

Abstract

BackgroundRecent studies in animal models have shown that statins can protect against renal failure independent of their lipid-lowering actions, and there is also an association between statin use and improved renal function after suprarenal aortic clamping. We investigated the hypothesis that post-ischemic acute renal failure could be ameliorated with atorvastatin (ATO) treatment and the possible molecular mechanisms in a model of ischemia–reperfusion (IR) in rats.MethodsTwenty-four male Sprague–Dawley rats were divided into three groups: sham, IR, and IR + ATO. ATO was given by a single intraperitoneal injection (10 mg/kg) 30 min before reperfusion in the IR + ATO group. The IR group and sham group received saline vehicle via the intraperitoneal route.ResultsAfter 24 h of IR, serum creatinine levels were increased in the IR group compared with the sham group (p < 0.001). ATO treatment reduced the elevation of serum creatinine level by 18% (p < 0.05) and significantly increased the creatinine clearance rate (p < 0.001). Concentrations of advanced oxidation protein products and malondialdehyde were reduced in the ATO group, approaching levels observed in sham-group rats. ATO treatment alleviated pathological changes in renal tubular cells. Protein and mRNA levels of intercellular adhesion molecule-1 and monocyte chemotactic protein-1 were reduced significantly.ConclusionsThese data suggest that direct protection of injured kidneys by ATO was possible even though the drug was injected 30 min before reperfusion, and that ATO may reduce IR injury by anti-inflammatory effects and by reducing oxidation stress.

Simvastatin attenuates renal ischemia/reperfusion injury from oxidative stress via targeting Nrf2/HO‑1 pathway

“…For instance, atorvastatin was found to attenuate rat renal I/R injury by reducing oxidative stress (12) and inhibiting active caspase-3 in rats (13). Simvastatin preserves microvascular barrier function by inhibiting the ischemia-induced release of vasoactive angiopoietin-2 and endothelin-1 as well as the tubule interstitial injury markers kidney injury molecule-1 and SCr following I/R (21).…”

“…In addition, short-term pre-treatment with statins (HMG-CoA reductase inhibitors) was demonstrated to reduce post-ischemic acute renal failure in a uninephrectomized rat model, which may be achieved due to their anti-inflammatory Simvastatin attenuates renal ischemia/reperfusion injury from oxidative stress via targeting Nrf2/HO-1 pathway action (11). For instance, atorvastatin was found to attenuate renal I/R injury in rats via its anti-inflammatory action and reducing oxidative stress (12), and improve renal function via inhibiting active caspase-3 in rats (13). Simvastatin has the potential to lower cholesterol in patients with cardiovascular disease (14,15).…”

The reno-protective effects of atorvastatin in crush syndrome and rhabdomyolysis:is there a dilemma?

“…Moreover, concentrations of advanced oxidation protein products and malondialdehyde were reduced in the atorvastatin group (15). Interestingly, in that study, atorvastatin was injected 30 min before reperfusion, not after reperfusion, and at a dose of 10 mg/kg, which was much higher than the doses used in our study.…”

Lipids, blood pressure and kidney update 2014

“…Statins administration might reduce oxidative stress, improve endothelial function and decrease inflammation [140,141]. Moreover, in experimental models of ischemiareperfusion, short-term statin treatment decreases renal dysfunction and inflammation [142,143]. Based on these data, the authors administrated high dose atorvastatin a day before surgery and continued until hospital discharge in statin naive patients; in those using statins prior to the study, treatment was administered until the day after surgery (https://www.asn-online.org/education/kidneyweek/ 2015/KW15_Late-Breakers.pdf ).…”