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

  • Authors:
    • Yu Zhang
    • Shu Rong
    • Yi Feng
    • Liqun Zhao
    • Jiang Hong
    • Ruilan Wang
    • Weijie Yuan
  • View Affiliations

  • Published online on: August 24, 2017     https://doi.org/10.3892/etm.2017.5023
  • Pages: 4460-4466
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Abstract

Ischemia‑reperfusion (I/R) injury of the kidneys is commonly encountered in the clinic. The present study assessed the efficacy of simvastatin in preventing I/R‑induced renal injury in a rat model and investigated the corresponding molecular mechanisms. Rats were divided into 3 groups, including a sham, I/R and I/R + simvastatin group. The results revealed that in the I/R group, the levels of blood urea nitrogen, serum creatinine and lactate dehydrogenase were significantly higher than those in the sham group, which was significantly inhibited by simvastatin pre‑treatment. I/R significantly decreased superoxide dismutase activity compared with that in the sham group, which was largely rescued by simvastatin. Furthermore, I/R significantly increased the malondialdehyde content compared with that in the sham group, which was reduced by simvastatin. Hematoxylin‑eosin staining revealed no obvious morphological abnormalities in the sham group, while I/R led to notable tubular cell swelling, vacuolization, cast formation and tubular necrosis, which was rescued by simvastatin. A terminal deoxynucleotidyl transferase‑mediated deoxyuridine triphosphate nick end labeling assay demonstrated that I/R significantly increased the number of apoptotic cells compared with that in the sham group, which was significantly inhibited by simvastatin. Western blot analysis demonstrated that simvastatin upregulated I/R‑induced increases of nuclear factor erythroid‑2‑related factor 2 (Nrf2) and anti‑oxidant enzyme heme oxygenase‑1 (HO‑1). Reverse‑transcription quantitative PCR indicated that changes in the mRNA levels of Nrf2 and HO‑1 were consistent with the western blot results. It was concluded that simvastatin treatment led to upregulation of HO‑1 protein levels through activating the Nrf2 signaling pathway to ultimately protect the kidneys from I/R‑associated oxidative damage.
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November-2017
Volume 14 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Zhang Y, Rong S, Feng Y, Zhao L, Hong J, Wang R and Yuan W: Simvastatin attenuates renal ischemia/reperfusion injury from oxidative stress via targeting Nrf2/HO‑1 pathway. Exp Ther Med 14: 4460-4466, 2017
APA
Zhang, Y., Rong, S., Feng, Y., Zhao, L., Hong, J., Wang, R., & Yuan, W. (2017). Simvastatin attenuates renal ischemia/reperfusion injury from oxidative stress via targeting Nrf2/HO‑1 pathway. Experimental and Therapeutic Medicine, 14, 4460-4466. https://doi.org/10.3892/etm.2017.5023
MLA
Zhang, Y., Rong, S., Feng, Y., Zhao, L., Hong, J., Wang, R., Yuan, W."Simvastatin attenuates renal ischemia/reperfusion injury from oxidative stress via targeting Nrf2/HO‑1 pathway". Experimental and Therapeutic Medicine 14.5 (2017): 4460-4466.
Chicago
Zhang, Y., Rong, S., Feng, Y., Zhao, L., Hong, J., Wang, R., Yuan, W."Simvastatin attenuates renal ischemia/reperfusion injury from oxidative stress via targeting Nrf2/HO‑1 pathway". Experimental and Therapeutic Medicine 14, no. 5 (2017): 4460-4466. https://doi.org/10.3892/etm.2017.5023