Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2020, 164(1):49-56 | DOI: 10.5507/bp.2019.006

Protective effects of resveratrol on acute kidney injury in rats with sepsis

Cong-Juan Luo, Feng Luo, Quan-Dong Bu, Wei Jiang, Wei Zhang, Xue-Mei Liu, Lin Che, Hong Luan, Hui Zhang, Rui-Xia Ma, Jian-Ping Sun, Yan Xu
The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao 266003, Shandong Province, China

Aim: To evaluate the protective effects of resveratrol on acute kidney injury (AKI) in septic rats.

Methods: A septic rat model was established by cecal ligation and puncture (CLP). A total of 108 male Sprague Dawley rats were randomly divided into an observation group, a 6 h resveratrol intervention group and a 12 h resveratrol intervention group. Then each group was subdivided into Sham, Sham + Res, CLP and CLP + Res groups. After surgery, the survival and morphological changes in kidney tissues were observed. Serum creatinine and urea nitrogen levels, expression of GRP78, BiP, IRE1 and p65 in kidney tissues, and serum levels of TNF-α, IL-1β, IL-6 and IL-10 were investigated.

Results: The survival rate of CLP + Res group (75.00%) significantly exceeded that of the CLP group (41.67%) (P<0.05). At postoperative 12 h, resveratrol significantly decreased serum creatinine and urea nitrogen levels (P<0.05). Resveratrol evidently relieved renal tubular swelling and luminal narrowing in CLP rats, and significantly reduced the high expressions of GRP78, BiP, phosphorylated IRE1 and p65 proteins (P<0.05). P65 was mainly located in the cytoplasm of Sham, Sham + Res and CLP + Res groups, and in the nucleus of the CLP group. At postoperative 12 h, resveratrol significantly reduced serum levels TNF-α, IL-1β and IL-6 in CLP rats (P<0.05), whereas elevated that of IL-10 (P<0.05).

Conclusion: Resveratrol significantly decreased the mortality rate of septic rats and alleviated AKI, probably by attenuating endoplasmic reticulum stress, inhibiting activation of the NF-κB pathway and mitigating the inflammatory response.

Keywords: resveratrol, sepsis, acute kidney injury, endoplasmic reticulum stress, inflammatory response

Received: September 12, 2018; Revised: February 26, 2019; Accepted: February 26, 2019; Prepublished online: April 17, 2019; Published: March 26, 2020  Show citation

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Luo, C., Luo, F., Bu, Q., Jiang, W., Zhang, W., Liu, X., ... Xu, Y. (2020). Protective effects of resveratrol on acute kidney injury in rats with sepsis. Biomedical papers164(1), 49-56. doi: 10.5507/bp.2019.006
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References

  1. Kaukonen KM, Bailey M, Pilcher D, Cooper DJ, Bellomo R. Systemic inflammatory response syndrome criteria in defining severe sepsis. N Engl J Med 2015;372(17):1629-38. Go to original source... Go to PubMed...
  2. Zhong W, Leto G, Wang L, Zeng G. Systemic inflammatory response syndrome after flexible ureteroscopic lithotripsy: a study of risk factors. J Endourol 2015;29(1):25-8. Go to original source... Go to PubMed...
  3. Delmas C, Zapetskaia T, Conil JM, Georges B, Vardon-Bounes F, Seguin T, Crognier L2, Fourcade O, Brouchet L, Minville V, Silva S. 3-month prognostic impact of severe acute renal failure under veno-venous ECMO support: Importance of time of onset. J Crit Care 2018;44:63-71. Go to original source... Go to PubMed...
  4. Schmitz M, Tillmann FP, Paluckaite A, Laufer EA, Rayner B, Rump LC, Heering PJ. Mortality risk factors in intensive care unit patients with acute kidney injury requiring renal replacement therapy: a retrospective cohort study. Clin Nephrol 2017;88(1):27-32. Go to original source... Go to PubMed...
  5. He T, Tao J, Wang X, Wang X. Effects of cisatracurium in combination with ventilation on inflammatory factors and immune variations in sepsis rats. Exp Ther Med 2018;15(5):4414-8. Go to original source... Go to PubMed...
  6. Peng N, Geng Y, Zhang S, Su L. Effects of ulinastatin on oxidative stress and renal injury in rats with severe heatstroke. Med J Chin People Liber Army 2015;40(5):354-7.
  7. Szeto HH, Liu S, Soong Y, Seshan SV, Cohen-Gould L, Manichev V, Feldman LC, Gustafsson T. Mitochondria protection after acute ischemia prevents prolonged upregulation of IL-1β and IL-18 and arrests CKD. J Am Soc Nephrol 2017;28(5):1437-49. Go to original source... Go to PubMed...
  8. Zarbock A, Kellum JA, Schmidt C, Van Aken H, Wempe C, Pavenstädt H, Boanta A, Gerß J, Meersch M. Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury: the ELAIN randomized clinical trial. JAMA 2016;315(20):2190-9. Go to original source... Go to PubMed...
  9. Herbert F, Tchitchek N, Bansal D, Jacques J, Pathak S, Bécavin C, Fesel C, Dalko E, Cazenave PA, Preda C, Ravindran B, Sharma S, Das B, Pied S. Evidence of IL-17, IP-10, and IL-10 involvement in multiple-organ dysfunction and IL-17 pathway in acute renal failure associated to Plasmodium falciparum malaria. J Transl Med 2015;13(1):369. Go to original source... Go to PubMed...
  10. Ozkok A, Ravichandran K, Wang Q, Ljubanovic D, Edelstein CL. NF-κB transcriptional inhibition ameliorates cisplatin-induced acute kidney injury (AKI). Toxicol Lett 2016;240(1):105-13. Go to original source... Go to PubMed...
  11. Khan MM, Yang WL, Brenner M, Bolognese AC, Wang P. Cold-inducible RNA-binding protein (CIRP) causes sepsis-associated acute lung injury via induction of endoplasmic reticulum stress. Sci Rep 2017;7:41363. Go to original source... Go to PubMed...
  12. Esposito V, Grosjean F, Tan J, Huang L, Zhu L, Chen J, Xiong H, Striker GE, Zheng F. CHOP deficiency results in elevated lipopolysaccharide-induced inflammation and kidney injury. Am J Physiol Renal Physiol 2012;304(4):F440-50. Go to original source... Go to PubMed...
  13. Calisto KL, Camacho AC, Mittestainer FC, Carvalho BM, Guadagnini D, Carvalheira JB, Saad MJ. RETRACTED ARTICLE: Diacerhein attenuates the inflammatory response and improves survival in a model of severe sepsis. Crit Care 2012;16(4):R158. Go to original source... Go to PubMed...
  14. Ma T, Han L, Gao Y, Li L, Shang X, Hu W, Xue C. The endoplasmic reticulum stress-mediated apoptosis signal pathway is involved in sepsis-induced abnormal lymphocyte apoptosis. Eur Surg Res 2008;41(2):219-25. Go to original source... Go to PubMed...
  15. Toliopoulos IK, Simos YV, Oikonomidis S, Karkabounas SC. Resveratrol diminishes platelet aggregation and increases susceptibility of K562 tumor cells to natural killer cells. Indian J Biochem Biophys 2013;50(1):14-8.
  16. Li T, Zhang J, Feng J, Li Q, Wu L, Ye Q, Sun J, Lin Y, Zhang M, Huang R, Cheng J, Cao Y, Xiang G, Zhang J, Wu Q. Resveratrol reduces acute lung injury in a LPS induced sepsis mouse model via activation of Sirt1. Mol Med Rep 2013;7(6):1889-95. Go to original source... Go to PubMed...
  17. Li C, Wang L, Huang K, Zheng L. Endoplasmic reticulum stress in retinal vascular degeneration: protective role of resveratrol. Invest Ophthalmol Vis Sci 2012;53(6):3241-9. Go to original source... Go to PubMed...
  18. Holthoff JH, Wang Z, Seely KA, Gokden N, Mayeux PR. Resveratrol improves renal microcirculation, protects the tubular epithelium, and prolongs survival in a mouse model of sepsis-induced acute kidney injury. Kidney Int 2012;81(4):370-8. Go to original source... Go to PubMed...
  19. Macdonald SP, Williams JM, Shetty A, Bellomo R, Finfer S, Shapiro N, Keijzers G. Review article: Sepsis in the emergency department - Part 1: Definitions and outcomes. Emerg Med Australas 2017;29(6):619-25. Go to original source... Go to PubMed...
  20. Gao X, Fu L, Xiao M, Xu C, Sun L, Zhang T, Zheng F, Mei C. The Nephroprotective Effect of Tauroursodeoxycholic Acid on Ischaemia/Reperfusion-Induced Acute Kidney Injury by Inhibiting Endoplasmic Reticulum Stress. Basic Clin Pharmacol Toxicol 2012;111(1):14-23. Go to original source... Go to PubMed...
  21. Cybulsky AV. Endoplasmic reticulum stress, the unfolded protein response and autophagy in kidney diseases. Nat Rev Nephrol 2017;13(11):681-96. Go to original source... Go to PubMed...
  22. Tran M, Tam D, Bardia A, Bhasin M, Rowe GC, Kher A, Zsengeller ZK, Akhavan-Sharif MR, Khankin EV, Saintgeniez M, David S, Burstein D, Karumanchi SA, Stillman IE, Arany Z, Parikh SM. PGC-1α promotes recovery after acute kidney injury during systemic inflammation in mice. J Clin Invest 2011;121(10):4003-14. Go to original source... Go to PubMed...
  23. Jung TW, Lee KT, Lee MW, Ka KH. SIRT1 attenuates palmitate-induced endoplasmic reticulum stress and insulin resistance in HepG2 cells via induction of oxygen-regulated protein 150. Biochem Biophys Res Commun 2012;422(2):229-32. Go to original source... Go to PubMed...

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