Skip to main content

Advertisement

Log in

Luteolin confers renoprotection against ischemia–reperfusion injury via involving Nrf2 pathway and regulating miR320

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

This work aims to evaluate the renoprotective effect of luteolin on expression of Nrf2 and miR320 in ischemia–reperfusion (I/R) injury in rats. Thirty rats were randomly divided into five groups; control, Luteolin (50 mg/kg), ischemia–reperfusion (I/R), DMSO (0/1%) + I/R and Luteolin+I/R, (n = 6 each). Administration of luteolin and DMSO was carried out by gavage for 3 days before renal I/R. Then, the rats were subjected to bilateral renal ischemia for 45 min and followed by reperfusion for 2 h. All rats were killed and the renal function, histological changes, oxidative stress degree, in all of groups were evaluated. In addition, the effects of luteolin on renal expression of Nrf2 and miR320 were examined by immunohistochemistry and real time- PCR. Luteolin significantly improved the creatinine (Cr) and blood urea nitrogen (BUN) levels in Luteolin + I/R group compared to I/R group (p < 0.001 and p < 0.001 respectively). Reduction of enzymatic activity of superoxide dismutase, glutathione peroxidase and catalase in I/R and DMSO + I/R groups, was significantly improved by Luteolin (p < 0.05) in Luteolin + I/R group. Pre-treatment with luteolin also resulted in significant reduction in tissue MDA level (p < 0.001), Nrf2 (p < 0.001) and miR320 expression (P < 0.05) that were increased by renal I/R. Also, the rats pretreated with luteolin had nearly normal structure of the kidney. These results indicate that luteolin protects the kidney against I/R injury via reducing oxidative stress, increasing antioxidant enzymes and reducing expression of Nrf2 and miR320.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Akan M, Ozbilgin S, Boztas N, Celik A, Ozkardesler S, Ergur BU, Guneli E, Sisman AR, Akokay P, Meseri R (2016) Effect of magnesium sulfate on renal ischemia-reperfusion injury in streptozotocin-induced diabetic rats. Eur Rev Med Pharmacol Sci 20(8):1642–1655

    CAS  PubMed  Google Scholar 

  2. Kosieradzki M, Rowinski W (2008) Ischemia/reperfusion injury in kidney transplantation: Mechanisms and prevention. Transplant Proc 40(10):3279–3288

    Article  CAS  PubMed  Google Scholar 

  3. Kalogeris T, Baines CP, Krenz M, Korthuis RJ (2012) Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol 298:229–317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Patschan D, Patschan S, Muller GA (2012) Inflammation and microvasculopathy in renal ischemia reperfusion injury. J Transplant 2012: Article ID 764154

  5. Yuan Q, Hong S, Han S, Zeng L, Liu F, Ding G, Kang Y, Mao J, Cai M, Zhu Y, Wang Q (2011) Preconditioning with physiological levels of ethanol protect kidney against ischemia/reperfusion injury by modulating oxidative stress. PLoS ONE 6:e25811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zhang G, Wang Q, Zhou Q, Wang R, Xu M, Wang H, Wang L, Wilcox CS, Liu R, Lai EY (2016) Protective effect of tempol on acute kidney injury through pi3 k/akt/nrf2 signaling pathway. Kidney Blood Press Res 41(2):129–138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kato M, Arce L, Natarajan R (2009) MicroRNAs and their role in progressive kidney diseases. Clin J Am Soc Nephrol 4(7):1255–1266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Güçlü A, Koçak C, Koçak FE, Akçılar R, Dodurga Y, Akçılar A, Seçme M (2016) Micro RNA-320 as a novel potential biomarker in renal ischemia reperfusion. Ren Fail 38(9):1468–1475

    Article  CAS  PubMed  Google Scholar 

  9. Nassirpour R, Mathur S, Gosink MM, Li Y, Shoieb AM, Wood J, O’Neil SP, Homer BL, Whiteley LO (2014) Identification of tubular injury microRNA biomarkers in urine: comparison of next-generation sequencing and qPCR based profiling platforms. BMC Genomics 15:485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wang F, Pu C, Zhou P, Wang P, Liang D, Wang Q, Hu Y, Li B, Hao X (2015) Cinnamaldehyde prevents endothelial dysfunction induced by high glucose by activating nrf2. Cell Physiol Biochem 36(1):315–324

    Article  CAS  PubMed  Google Scholar 

  11. Akbari G, Mard SA, Dianat M, Mansouri E (2017) The hepatoprotective and MicroRNAs downregulatory effects of crocin following hepatic ischemia-reperfusion injury in rats. Oxidative Medicine and Cellular Longevity 2017:Article ID 1702967

  12. Wang J, Hu X, Xie J, Xu W, Jiang H (2015) Beta-1-adrenergic receptors mediate nrf2-ho-1-hmgb1 axis regulation to attenuate hypoxia/reoxygenation-induced cardiomyocytes injury in vitro. Cell Physiol Biochem 35(2):767–777

    Article  CAS  PubMed  Google Scholar 

  13. Liu M, Grigoryev DN, Crow MT, Haas M, Yamamoto M, Reddy SP, Rabb H (2009) Transcription factor Nrf2 is protective during ischemic and nephrotoxic acute kidney injury in mice. Kidney Int 76(3):277–285

    Article  CAS  PubMed  Google Scholar 

  14. Lopez-Lazaro M (2009) Distribution and biological activities of the flavonoid luteolin. Mini Rev Med Chem 9(1):31–59

    Article  CAS  PubMed  Google Scholar 

  15. Kang KP, Park SK, Kim DH, Sung MJ, Jung YJ, Lee AS, Lee JE, Ramkumar KM, Lee S, Park MH, Roh SG, Kim W (2011) Luteolin ameliorates cisplatin-induced acute kidney injury in mice by regulation of p53-dependent renal tubular apoptosis. Nephrol Dial Transplant 26(3):814–822

    Article  CAS  PubMed  Google Scholar 

  16. Arslan BY, Arslan F, Erkalp K, Alagöl A, Sevdi MS, Yıldız G, Küçük SH, Altınay S (2016) Luteolin ameliorates colistin-induced nephrotoxicity in the rat models. Ren Fail 38(10):1735–1740

    Article  CAS  PubMed  Google Scholar 

  17. Domitrović R, Cvijanović O, Pugel EP, Zagorac GB, Mahmutefendić H, Škoda M (2013) Luteolin amelioratescisplatin-induced nephrotoxicity in mice through inhibition of platinum accumulation, inflammation and apoptosis in the kidney. Toxicology 310:115–123

    Article  CAS  PubMed  Google Scholar 

  18. Xin SB, Yan H, Ma J, Sun Q, Shen L (2016) Protective effects of luteolin on lipopolysaccharide-induced acute renal injury in mice. Med Sci Monit 22:5173–5180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hong X, Zhao X, Wang G, Zhang Z, Pei H, Liu Z (2017) Luteolin treatment protects against renal ischemia-reperfusion injury in rats. mediators of inflammation 2017: pages 10, Article ID 9783893

  20. Mansouri E, Jangaran A, Ashtari A (2017) Protective effect of pravastatin on doxorubicin-induced hepatotoxicity. Bratisl Lek Listy 118(5):273–277

    CAS  PubMed  Google Scholar 

  21. Kooti W, Mansouri E, Assarehzadegan MA, Nejad-Dehbashi F (2017) Effect of pravastatin on levels of filtration slit diaphragm protein and oxidative stress in doxorubicin-induced nephrotoxicity. Indian J Pharm Educ Res 51(1):77–82

    Article  CAS  Google Scholar 

  22. Brooks C, Wei Q, Cho SG, Dong Z (2009) Regulation of mitochondrial dynamics in acute kidney injury in cell culture and rodent models. J Clin Invest 119(5):1275–1285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Karimi A, Absalan F, Khorsandi L, Valizadeh A, Mansouri E (2017) Sodium hydrogen sulfide (NaHS) ameliorates alterations caused by cisplatin in filtration slit diaphragm and podocyte cytoskeletal in rat kidneys. J Nephropathol 6(3):150–156

    Article  PubMed  PubMed Central  Google Scholar 

  24. Khorsandi L, Orazizadeh M, Moradi-Gharibvand N, Hemadi M, Mansouri E (2017) Beneficial effects of quercetin on titanium dioxide nanoparticles induced spermatogenesis defects in mice. Environ Sci Pollut Res 24:5595–5606

    Article  CAS  Google Scholar 

  25. Yang Y, Song M, Liu Y, Liu H, Sun L, Peng Y, Liu F, Venkatachalam MA, Dong Z (2016) Renoprotective approaches and strategies in acute kidney injury. Pharmacol Ther 163:58–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Karimi G, Ramezani M, Tahoonian Z (2005) Cisplatin nephrotoxicity and protection by milk thistle extract in rats. Evid Based Complement Alternat Med 2(3):383–386

    Article  PubMed  PubMed Central  Google Scholar 

  27. Chen G, Fu Y, Wu X (2012) Protective effect of salvia miltiorrhiza extract against renal ischemia-reperfusion-induced injury in rats. Molecules 17(2):1191–1202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Rovcanin B, Medic B, Kocic G, Cebovic T, Ristic M, Prostran M (2016) Molecular dissection of renal ischemia-reperfusion: oxidative stress and cellular events. Curr Med Chem 23(19):1965–1980

    Article  CAS  PubMed  Google Scholar 

  29. Kalogeris T, Bao Y, Korthuis RJ (2014) Mitochondrial reactive oxygen species: a double edged sword in ischemia/reperfusion vs preconditioning. Redox Biol 2:702–714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Finaud J, Lac G, Filaire E (2006) Oxidative stress: relationship with exercise and training. Sports Med 36(4):327–358

    Article  PubMed  Google Scholar 

  31. Sureshbabu A, Ryter SW, Choi ME (2015) Oxidative stress and autophagy: crucial modulators of kidney injury. Redox Biol 4:208–214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wang F, Yu G, Liu SY, Li JB, Wang JF, Bo LL, Qian LR, Sun XJ, Deng XM (2011) Hydrogen-rich saline protects against renal ischemia/reperfusion injury in rats. J Surg Res 167(2):e339–e344

    Article  CAS  PubMed  Google Scholar 

  33. Yu D, Li M, Tian Y, Liu J, Shang J (2015) Luteolin inhibits ROS-activated MAPK pathway in myocardial ischemia/reperfusion injury. Life Sci 122:15–25

    Article  CAS  PubMed  Google Scholar 

  34. Tai M, Zhang J, Song S, Miao R, Liu S, Pang Q, Wu Q, Liu C (2015) Protective effects of luteolin against acetaminophen-induced acute liver failure in mouse. Int Immunopharmacol 27(1):164–170

    Article  CAS  PubMed  Google Scholar 

  35. Xu Y, Zhang J, Liu J, Li S, Li C, Wang W, Ma R, Liu Y (2015) Luteolin attenuate the Dgalactose-induced renal damage by attenuation of oxidative stress and inflammation. Nat Prod Res 29(11):1078–1082

    Article  CAS  PubMed  Google Scholar 

  36. Kim HJ, Vaziri ND (2010) Contribution of impaired Nrf2-Keap1 pathway to oxidative stress and inflammation in chronic renal failure. Am J Physiol Renal Physiol 298(3):F662–F671

    Article  CAS  PubMed  Google Scholar 

  37. Kobayashi M, Yamamoto M (2005) Molecular mechanisms activating the Nrf2-Keap1 pathway of antioxidant gene regulation. Antioxid Redox Signal 7(3-4):385–394

    Article  CAS  PubMed  Google Scholar 

  38. Tang X, Wang H, Fan L, Wu X, Xin A, Ren H, Wang XJ (2011) Luteolin inhibits Nrf2 leading to negative regulation of the Nrf2/ARE pathway and sensitization of human lung carcinoma A549 cells to therapeutic drugs. Free Radic Biol Med 50(11):1599–1609

    Article  CAS  PubMed  Google Scholar 

  39. Lin CW, Wu MJ, Liu IY, Su JD, Yen JH (2010) Neurotrophic and cytoprotective action of luteolin in PC12 cells through ERK-dependent induction of Nrf2-driven HO-1 expression. J Agric Food Chem 58(7):4477–4486

    Article  CAS  PubMed  Google Scholar 

  40. Ren XP, Wu J, Wang X, Sartor MA, Jones K, Qian J, Nicolaou P, Pritchard TJ, Fan GC (2009) MicroRNA-320 is involved in the regulation of cardiac ischemia/reperfusion injury by targeting heat-shock protein 20. Circulation 119(17):2357–2366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This article was extracted from MSc student thesis (Sanaz Moradi). The authors thank the Vice Chancellor of Research Affairs of Ahvaz Jundishapur University of Medical Sciences for financial support of this study [Grant No. CMRC-9621].

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Esrafil Mansouri.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures were done in accordance with the ethics committee of Ahvaz Jundishapur University of Medical Sciences.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kalbolandi, S.M., Gorji, A.V., Babaahmadi-Rezaei, H. et al. Luteolin confers renoprotection against ischemia–reperfusion injury via involving Nrf2 pathway and regulating miR320. Mol Biol Rep 46, 4039–4047 (2019). https://doi.org/10.1007/s11033-019-04853-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-019-04853-0

Keywords

Navigation