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Article

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 / Copyright

    Affiliations: Department of Emergency Intensive Medicine, Shanghai General Hospital of Nanjing Medical University, Shanghai 200082, P.R. China, Department of Nephrology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200082, P.R. China
  • Pages: 4460-4466
    |
    Published online on: August 24, 2017
       https://doi.org/10.3892/etm.2017.5023
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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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1 

Anaya-Prado R, Toledo-Pereyra LH, Lentsch AB and Ward PA: Ischemia/reperfusion injury. J Surg Res. 105:248–258. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Nath KA and Norby SM: Reactive oxygen species and acute renal failure. Am J Med. 109:665–678. 2000. View Article : Google Scholar : PubMed/NCBI

3 

Tsuda H, Kawada N, Kaimori JY, Kitamura H, Moriyama T, Rakugi H, Takahara S and Isaka Y: Febuxostat suppressed renal ischemia-reperfusion injury via reduced oxidative stress. Biochem Biophys Res Commun. 427:266–272. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Feng L, Ke N, Cheng F, Guo Y, Li S, Li Q and Li Y: The protective mechanism of ligustrazine against renal ischemia/reperfusion injury. J Surg Res. 166:298–305. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Shokeir AA, Barakat N, Hussein AM, Awadalla A, Harraz AM, Khater S, Hemmaid K and Kamal AI: Activation of Nrf2 by ischemic preconditioning and sulforaphane in renal ischemia/reperfusion injury: A comparative experimental study. Physiol Res. 64:313–323. 2015.PubMed/NCBI

6 

Jiang G, Liu X, Wang M, Chen H, Chen Z and Qiu T: Oxymatrine ameliorates renal ischemia-reperfusion injury from oxidative stress through Nrf2/HO-1 pathway. Acta Cir Bras. 30:422–429. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Lin L, Zheng J, Zhu W and Jia N: Nephroprotective effect of gelsemine against cisplatin-induced toxicity is mediated via attenuation of oxidative stress. Cell Biochem Biophys. 71:535–541. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Jaiswal AK: Nrf2 signaling in coordinated activation of antioxidant gene expression. Free Radic Biol Med. 36:1199–1207. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Zhang L, Zhu Z, Liu J, Zhu Z and Hu Z: Protective effect of N-acetylcysteine (NAC) on renal ischemia/reperfusion injury through Nrf2 signaling pathway. J Recept Signal Transduct Res. 34:396–400. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Goldstein JL and Brown MS: Regulation of the mevalonate pathway. Nature. 343:425–430. 1990. View Article : Google Scholar : PubMed/NCBI

11 

Gueler F, Rong S, Park JK, Fiebeler A, Menne J, Elger M, Mueller DN, Hampich F, Dechend R and Kunter U: Postischemic acute renal failure is reduced by short-term statin treatment in a rat model. J Am Soc Nephrol. 13:2288–2298. 2002. View Article : Google Scholar : PubMed/NCBI

12 

Wu K, Lei W, Tian J and Li H: Atorvastatin treatment attenuates renal injury in an experimental model of ischemia-reperfusion in rats. BMC Nephrol. 15:142014. View Article : Google Scholar : PubMed/NCBI

13 

Haylor JL, Harris KP, Nicholson ML, Waller HL, Huang Q and Yang B: Atorvastatin improving renal ischemia reperfusion injury via direct inhibition of active caspase-3 in rats. Exp Biol Med (Maywood). 236:755–763. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: The scandinavian simvastatin survival study (4S). Lancet. 344:1383–1389. 1994.PubMed/NCBI

15 

Levine GN, Keaney JF Jr and Vita JA: Cholesterol reduction in cardiovascular disease. Clinical benefits and possible mechanisms. N Engl J Med. 332:512–521. 1995. View Article : Google Scholar : PubMed/NCBI

16 

Endres M, Laufs U, Huang Z, Nakamura T, Huang P, Moskowitz MA and Liao JK: Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad Sci U S A. 95:8880–8885. 1998. View Article : Google Scholar : PubMed/NCBI

17 

Pruefer D, Scalia R and Lefer AM: Simvastatin inhibits leukocyte-endothelial cell interactions and protects against inflammatory processes in normocholesterolemic rats. Arterioscler Thromb Vasc Biol. 19:2894–2900. 1999. View Article : Google Scholar : PubMed/NCBI

18 

Lefer AM, Campbell B, Shin YK, Scalia R, Hayward R and Lefer DJ: Simvastatin preserves the ischemic-reperfused myocardium in normocholesterolemic rat hearts. Circulation. 100:178–184. 1999. View Article : Google Scholar : PubMed/NCBI

19 

McCord JM: The evolution of free radicals and oxidative stress. Am J Med. 108:652–659. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Tuuminen R, Nykänen AI, Saharinen P, Gautam P, Keränen MA, Arnaudova R, Rouvinen E, Helin H, Tammi R and Rilla K: Donor simvastatin treatment prevents ischemia-reperfusion and acute kidney injury by preserving microvascular barrier function. Am J Transplant. 13:2019–2034. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Todorovic Z, Nesic Z, Stojanović R, Basta-Jovanović G, Radojevic-Skodrić S, Velicković R, Chatterjee PK, Thiemermann C and Prostran M: Acute protective effects of simvastatin in the rat model of renal ischemia-reperfusion injury: It is never too late for the pretreatment. J Pharmacol Sci. 107:465–470. 2008. View Article : Google Scholar : PubMed/NCBI

23 

McCord JM: Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med. 312:159–163. 1985. View Article : Google Scholar : PubMed/NCBI

24 

Halliwell B and Gutteridge J.M.C: Free radicals, other reactive species and diseaseFree Radicals in Biology and Medicine. Third. Oxford University Press; Oxford: pp. 617–783. 1999

25 

Guidet BR and Sudh SV: In vivo generation of hydrogen peroxide by rat kidney cortex and glomeruli. Am J Physiol. 256:F158–F164. 1989.PubMed/NCBI

26 

Andreucci VE and Fine LG: Reactive oxygen species and renal injuryInternational Yearbook of Nephrology. 1st. Kluwer Academic Press; New York, NY: pp. 47–69. 1991

27 

Szeto HH: Mitochondria-targeted cytoprotective peptides for ischemia-reperfusion injury. Antioxid Redox Signal. 10:601–619. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Tartibian B and Maleki BH: The effects of honey supplementation on seminal plasma cytokines, oxidative stress biomarkers and antioxidants during 8 weeks of intensive cycling training. J Androl. 33:449–461. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Daemen MA, van de Ven MW, Heineman E and Buurman WA: Involvement of endogenous interleukin-10 and tumor necrosis factor-alpha in renal ischemia-reperfusion injury. Transplantation. 67:792–800. 1999. View Article : Google Scholar : PubMed/NCBI

30 

Daemen MA, van 't Veer C, Denecker G, Heemskerk VH, Wolfs TG, Clauss M, Vandenabeele P and Buurman WA: Inhibition of apoptosis induced by ischemia-reperfusion prevents inflammation. J Clin Invest. 104:541–549. 1999. View Article : Google Scholar : PubMed/NCBI

31 

Kim HJ and Vaziri ND: Contribution of impaired Nrf2-Keap1 pathway to oxidative stress and inflammation in chronic renal failure. Am J Physiol Renal Physiol. 298:F662–671. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Kobayashi M and Yamamoto M: Molecular mechanisms activating the Nrf2-Keap1 pathway of antioxidant gene regulation. Antioxid Redox Signal. 7:385–394. 2005. View Article : Google Scholar : PubMed/NCBI

33 

Chartoumpekis D, Ziros PG, Psyrogiannis A, Kyriazopoulou V, Papavassiliou AG and Habeos IG: Simvastatin lowers reactive oxygen species level by Nrf2 activation via PI3K/Akt pathway. Biochem Biophys Res Commun. 396:463–466. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Jang HJ, Hong EM, Kim M, Kim JH, Jang J, Park SW, Byun HW, Koh DH, Choi MH, Kae SH and Lee J: Simvastatin induces heme oxygenase-1 via NF-E2-related factor 2 (Nrf2) activation through ERK and PI3K/Akt pathway in colon cancer. Oncotarget. 7:46219–46229. 2016. View Article : Google Scholar : PubMed/NCBI

35 

Habeos IG, Ziros PG, Chartoumpekis D, Psyrogiannis A, Kyriazopoulou V and Papavassiliou AG: Simvastatin activates Keap1/Nrf2 signaling in rat liver. J Mol Med (Berl). 86:1279–1285. 2008. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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