Introduction: Although simvastatin attenuates renal injury in several ways, its poor solubility and bioavailability may reduce its efficiency. This study evaluated the effect of simvastatin-loaded nano-niosomes against myocardial ischemia/reperfusion (MI/R)-induced kidney failure and compared its efficiency with simvastatin.
Methods: Nano-niosomes were prepared using the surface-active agent film hydration method. For inducing MI/R, the left anterior descending artery (LAD) was ligated, and then recirculation was established. Drug formulations at a concentration of 3 mg/kg were administered into the myocardial tissue. Western blot assay was applied to measure protein levels. An ELISA assay was used to evaluate the expression of inflammatory cytokines, oxidative stress markers, and markers of renal function. H&E staining was done to determine tissue damage.
Results: The induction of MI/R in rats increased serum levels of creatinine, BUN, and uric acid; elevated levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-11), NF-κB, BAX, and caspase-3 in renal tissue; and decreased the activities of antioxidant enzymes SOD, GPX, and catalase as well as Bcl-2 protein in renal tissue. Although all of these changes were neutralized by medication with simvastatin and simvastatin-loaded nano-niosomes, simvastatin-loaded nano-niosomes had a more powerful impact on reducing MI/R-induced renal injury compared to only simvastatin.
Conclusion: The outcomes conclude that nano-niosomes can be considered a good candidate to improve the efficiency of simvastatin against MI/R-induced renal injury. Simvastatin-loaded nano-niosomes are capable of reducing MI/R-induced renal injury and improving renal function by reducing inflammation, suppressing oxidative stress, targeting NF-κB protein, and attenuating apoptotic cell death.