Naringin Affects Caspase-3, IL-1β, and HIF-1α Levels in Experimental Kidney Ischemia-Reperfusion in Rats


Cite item

Full Text

Abstract

Background:Microvascular dysfunction develops in tissues after Ischemia-Reperfusion (IR). The current study aimed to determine the effect of naringin supplementation on kidney caspase-3, IL-1β, and HIF-1α levels and kidney histology in rats undergoing unilateral nephrectomy and kidney-ischemia reperfusion.

Methods:The study was conducted on 8-12 weeks old 40 Wistar-type male rats. Experimental renal ischemia- reperfusion and unilateral nephrectomy were performed under general anesthesia in rats. Experimental groups were formed as follows: 1-Control group, 2-Sham control + Vehicle group, 3- Renal ischemia-reperfusion (Renal I+R) + Vehicle group, 4-Renal I+R + Naringin (50 mg/kg/day) group (3 days application) group, 5-Renal I+R + Naringin (100 mg/kg/day) group (3 days supplementation). Nephrectomy in the left kidneys and the ischemia for 45 minutes and reperfusion in the right kidneys followed by 72 hours of reperfusion. Naringin was administered intraperitoneally at the beginning of the reperfusion, 24 hours and 48 hours later. At the end of the experiments, blood was first taken from the heart in animals under general anesthesia. Then, the animals were killed by cervical dislocation, and kidney tissue samples were taken. Tissues were evaluated for caspase-3, IL-1β, and HIF-1α as well as histologically.

Results:As a result of ischemia in kidney tissues, HIF-1α decreased, while caspase-3 and IL-1β increased. IR also caused damage to the kidney tissue. However, naringin supplementation corrected the deterioration to a certain extent.

Conclusion:The results of the study showed that naringin may have protective effects on kidney damage due to anti-inflammatory and antiapoptosis mechanisms caused by unilateral nephrectomy and IR in rats.

About the authors

Esra Danis

Department of Physiology, Medical Faculty,, Selcuk University,

Email: info@benthamscience.net

Gozde Acar

Department of Physiology, Medical Faculty, Selçuk University

Email: info@benthamscience.net

Dervis Dasdelen

Department of Physiology, Medical Faculty,, Karamanoglu Mehmetbey University

Email: info@benthamscience.net

Merve Solmaz

Department of Histology, Medical Faculty,, Selçuk University

Email: info@benthamscience.net

Rasim Mogulkoc

Department of Physiology, Medical Faculty, Selçuk University

Author for correspondence.
Email: info@benthamscience.net

Abdulkerim Baltaci

Department of Physiology, Medical Faculty, Selçuk University

Email: info@benthamscience.net

References

  1. Giaccia AJ, Simon MC, Johnson R. The biology of hypoxia: The role of oxygen sensing in development, normal function, and disease. Genes Dev 2004; 18(18): 2183-94. doi: 10.1101/gad.1243304 PMID: 15371333
  2. Giordano FJ. Oxygen, oxidative stress, hypoxia, and heart failure. J Clin Invest 2005; 115(3): 500-8. doi: 10.1172/JCI200524408 PMID: 15765131
  3. Devarajan P. Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol 2006; 17(6): 1503-20. doi: 10.1681/ASN.2006010017 PMID: 16707563
  4. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Ischemia/Reperfusion. Compr Physiol 2016; 7(1): 113-70. doi: 10.1002/cphy.c160006 PMID: 28135002
  5. Wu Y, Chen W, Zhang Y, et al. Potent therapy and transcriptional profile of combined erythropoietin-derived peptide cyclic helix B surface peptide and caspase-3 siRNA against kidney ischemia/reperfusion injury in mice. J Pharmacol Exp Ther 2020; 375(1): 92-103. doi: 10.1124/jpet.120.000092 PMID: 32759272
  6. Dinarello CA. An expanding role for interleukin-1 blockade from gout to cancer. Mol Med 2014; 20(S1) (Suppl. 1): S43-58. doi: 10.2119/molmed.2014.00232 PMID: 25549233
  7. Garlanda C, Dinarello CA, Mantovani A. The interleukin-1 family: Back to the future. Immunity 2013; 39(6): 1003-18. doi: 10.1016/j.immuni.2013.11.010 PMID: 24332029
  8. Cordero MD, Alcocer-Gómez E, Ryffel B. Gain of function mutation and inflammasome driven diseases in human and mouse models. J Autoimmun 2018; 91: 13-22. doi: 10.1016/j.jaut.2018.03.002 PMID: 29610014
  9. Liu Z, Meng Y, Miao Y, Yu L, Yu Q. Propofol reduces renal ischemia/reperfusion-induced acute lung injury by stimulating sirtuin 1 and inhibiting pyroptosis. Aging (Albany NY) 2021; 13(1): 865-76. doi: 10.18632/aging.202191 PMID: 33260147
  10. Zeng X, Su W, Zheng Y, et al. Pharmacokinetics, tissue distribution, metabolism, and excretion of naringin in aged rats. Front Pharmacol 2019; 10: 34. doi: 10.3389/fphar.2019.00034 PMID: 30761003
  11. Amini N, Sarkaki A, Dianat M, Mard SA, Ahangarpour A, Badavi M. Naringin and trimetazidine improve baroreflex sensitivity and nucleus tractus solitarius electrical activity in renal ischemia-reperfusion injury. Arq Bras Cardiol 2021; 117(2): 290-7. doi: 10.36660/abc.20200121 PMID: 34495221
  12. Liu L, Zhang P, Bai M, et al. p53 upregulated by HIF-1α promotes hypoxia-induced G2/M arrest and renal fibrosis in vitro and in vivo. J Mol Cell Biol 2019; 11(5): 371-82. doi: 10.1093/jmcb/mjy042 PMID: 30032308
  13. Shan Y, Chen D, Hu B, et al. Allicin ameliorates renal ischemia/ reperfusion injury via inhibition of oxidative stress and inflammation in rats. Biomed Pharmacother 2021; 142: 112077. doi: 10.1016/j.biopha.2021.112077 PMID: 34426252
  14. Wang R, Wu G, Dai T, et al. Naringin attenuates renal interstitial fibrosis by regulating the TGF-β/Smad signaling pathway and inflammation. Exp Ther Med 2020; 21(1): 66. doi: 10.3892/etm.2020.9498 PMID: 33365066
  15. Khalid U, Pino-Chavez G, Nesargikar P, et al. Kidney ischaemia reperfusion injury in the rat: The EGTI scoring system as a valid and reliable tool for histological assessment. J Histol Histopathol 2016; 3(1): 1. doi: 10.7243/2055-091X-3-1
  16. Liu H, Li Y, Xiong J. The role of hypoxia-inducible factor-1 alpha in renal disease. Molecules 2022; 27(21): 7318. doi: 10.3390/molecules27217318 PMID: 36364144
  17. Movafagh S, Crook S, Vo K. Regulation of hypoxia-inducible factor-1a by reactive oxygen species: New developments in an old debate. J Cell Biochem 2015; 116(5): 696-703. doi: 10.1002/jcb.25074 PMID: 25546605
  18. Agarwal A, Nick HS. Renal response to tissue injury: Lessons from heme oxygenase-1 GeneAblation and expression. J Am Soc Nephrol 2000; 11(5): 965-73. doi: 10.1681/ASN.V115965 PMID: 10770977
  19. Moore E, Bellomo R. Erythropoietin (EPO) in acute kidney injury. Ann Intensive Care 2011; 1(1): 3. doi: 10.1186/2110-5820-1-3 PMID: 21906325
  20. Schietke R, Warnecke C, Wacker I, et al. The lysyl oxidases LOX and LOXL2 are necessary and sufficient to repress E-cadherin in hypoxia: Insights into cellular transformation processes mediated by HIF-1. J Biol Chem 2010; 285(9): 6658-69. doi: 10.1074/jbc.M109.042424 PMID: 20026874
  21. Warnecke C, Zaborowska Z, Kurreck J, et al. Differentiating the functional role of hypoxia-inducible factor (HIF)-1α and HIF-2α (EPAS-1) by the use of RNA interference: Erythropoietin is a HIF-2α target gene in Hep3B and Kelly cells. FASEB J 2004; 18(12): 1462-4. doi: 10.1096/fj.04-1640fje PMID: 15240563
  22. Li P, Liu Y, Qin X, et al. SIRT1 attenuates renal fibrosis by repressing HIF-2α. Cell Death Discov 2021; 7(1): 59. doi: 10.1038/s41420-021-00443-x PMID: 33414425
  23. Pan SY, Tsai PZ, Chou YH, et al. Kidney pericyte hypoxia-inducible factor regulates erythropoiesis but not kidney fibrosis. Kidney Int 2021; 99(6): 1354-68. doi: 10.1016/j.kint.2021.01.017 PMID: 33812664
  24. Tanaka T, Wiesener M, Bernhardt W, Eckardt KU, Warnecke C. The human HIF (hypoxia-inducible factor)-3α gene is a HIF-1 target gene and may modulate hypoxic gene induction. Biochem J 2009; 424(1): 143-51. doi: 10.1042/BJ20090120 PMID: 19694616
  25. Kimura K, Iwano M, Higgins DF, et al. Stable expression of HIF-1α in tubular epithelial cells promotes interstitial fibrosis. Am J Physiol Renal Physiol 2008; 295(4): F1023-9. doi: 10.1152/ajprenal.90209.2008 PMID: 18667485
  26. Baumann B, Hayashida T, Liang X, Schnaper HW. Hypoxia-inducible factor-1α promotes glomerulosclerosis and regulates COL1A2 expression through interactions with Smad3. Kidney Int 2016; 90(4): 797-808. doi: 10.1016/j.kint.2016.05.026 PMID: 27503806
  27. Meng F. A novel role of HIF-1α/PROX-1/LYVE-1 axis on tissue regeneration after renal ischaemia/reperfusion in mice. Arch Physiol Biochem 2019; 125(4): 321-31. doi: 10.1080/13813455.2018.1459728 PMID: 29633855
  28. Han M, Li S, Xie H, et al. Activation of TGR5 restores AQP2 expression via the HIF pathway in renal ischemia-reperfusion injury. Am J Physiol Renal Physiol 2021; 320(3): F308-21. doi: 10.1152/ajprenal.00577.2020 PMID: 33427060
  29. Cienfuegos-Pecina E, Ibarra-Rivera TR, Saucedo AL, et al. Effect of sodium ( S )-2-hydroxyglutarate in male, and succinic acid in female Wistar rats against renal ischemia-reperfusion injury, suggesting a role of the HIF-1 pathway. PeerJ 2020; 8: e9438. doi: 10.7717/peerj.9438 PMID: 32728491
  30. Yan B, Min SJ, Xu B, et al. The protective effects of exogenous spermine on renal ischemia-reperfusion injury in rats. Transl Androl Urol 2021; 10(5): 2051-66. doi: 10.21037/tau-21-280 PMID: 34159086
  31. Li BY, Liu Y, Li ZH, et al. Dexmedetomidine promotes the recovery of renal function and reduces the inflammatory level in renal ischemia-reperfusion injury rats through PI3K/Akt/HIF-1α signaling pathway. Eur Rev Med Pharmacol Sci 2020; 24(23): 12400-7. doi: 10.26355/eurrev_202012_24035 PMID: 33336761
  32. Barakat M, Hussein AM, Salama MF, et al. Possible underlying mechanisms for the renoprotective effect of retinoic acid-pretreated Wharton’s jelly mesenchymal stem cells against renal ischemia/reperfusion injury. Cells 2022; 11(13): 1997. doi: 10.3390/cells11131997 PMID: 35805083
  33. Zhang B, Wan S, Liu H, et al. Naringenin alleviates renal ischemia reperfusion injury by suppressing ER stress-induced pyroptosis and apoptosis through activating Nrf2/HO-1 signaling pathway. Oxid Med Cell Longev 2022; 2022: 1-24. doi: 10.1155/2022/5992436 PMID: 36262286
  34. El-Sayed SS, Shahin RM, Fahmy A, Elshazly SM. Quercetin ameliorated remote myocardial injury induced by renal ischemia/reperfusion in rats: Role of Rho-kinase and hydrogen sulfide. Life Sci 2021; 287: 120144. doi: 10.1016/j.lfs.2021.120144 PMID: 34785193
  35. Zhang S, Xu X, Huang Y, et al. Anisodamine ameliorates ischemia/reperfusion-induced renal injury in rats through activation of the extracellular signal-regulated kinase (ERK) pathway and anti-apoptotic effect. Pharmazie 2021; 76(5): 220-4. doi: 10.1691/ph.2021.1302 PMID: 33964996
  36. Wang ZS, Zhou HH, Han Q, Guo YL, Li ZY. Effects of grape seed proanthocyanidin B2 pretreatment on oxidative stress and renal tubular epithelial cell apoptosis after renal ischemia reperfusion in mice. Acta Cirúrgica Brasileira 35 2020.
  37. Meng X, Wei M, Wang D, et al. The protective effect of hesperidin against renal ischemia-reperfusion injury involves the TLR-4/NF-κB/iNOS pathway in rats. Physiol Int 2020; 107(1): 82-91. doi: 10.1556/2060.2020.00003 PMID: 32491283
  38. Liu Y, Shi B, Li Y, Zhang H. Protective effect of luteolin against renal ischemia/reperfusion injury via modulation of pro-inflammatory cytokines, oxidative stress and apoptosis for possible benefit in kidney transplant. Med Sci Monit 2017; 23: 5720-7. doi: 10.12659/MSM.903253 PMID: 29196613
  39. Rider P, Carmi Y, Voronov E, Apte RN. Interleukin-1α. Semin Immunol 2013; 25(6): 430-8. doi: 10.1016/j.smim.2013.10.005
  40. Kezić A, Stajic N, Thaiss F. Innate immune response in kidney ischemia/reperfusion injury: Potential target for therapy. J Immunol Res 2017; 2017: 1-10. doi: 10.1155/2017/6305439 PMID: 28676864
  41. Aal-Aaboda M, Abu Raghif AR, Hadi NR. Effect of lipopolysaccharide from Rhodobacter sphaeroides on inflammatory pathway and oxidative stress in renal ischemia/reperfusion injury in male rats. Arch Razi Inst 2021; 76(4): 1013-24. doi: 10.22092/ari.2021.356003.1761 PMID: 35096337
  42. Mozaffari Godarzi S, Valizade Gorji A, Gholizadeh B, Mard SA, Mansouri E. Antioxidant effect of p-coumaric acid on interleukin 1-β and tumor necrosis factor-α in rats with renal ischemic reperfusion. Nefrología (English Edition) 2020; 40(3): 311-9. doi: 10.1016/j.nefroe.2020.06.017 PMID: 31892486
  43. Perez-Meseguer J, Torres-González L, Gutiérrez-González JA, et al. Anti-inflammatory and nephroprotective activity of Juglans mollis against renal ischemia–reperfusion damage in a Wistar rat model. BMC Complement Altern Med 2019; 19(1): 186. doi: 10.1186/s12906-019-2604-7 PMID: 31349827
  44. Ahmed S, Khan H, Aschner M, Hasan MM, Hassan STS. Therapeutic potential of naringin in neurological disorders. Food Chem Toxicol 2019; 132: 110646. doi: 10.1016/j.fct.2019.110646 PMID: 31252025
  45. Raja Kumar S, Mohd Ramli ES, Abdul Nasir NA, Ismail NHM, Mohd Fahami NA. Preventive effect of naringin on metabolic syndrome and its mechanism of action: A systematic review. Evid Based Complement Alternat Med 2019; 2019: 1-11. doi: 10.1155/2019/9752826 PMID: 30854019
  46. Heidary Moghaddam R, Samimi Z, Moradi SZ, Little PJ, Xu S, Farzaei MH. Naringenin and naringin in cardiovascular disease prevention: A preclinical review. Eur J Pharmacol 2020; 887: 173535. doi: 10.1016/j.ejphar.2020.173535 PMID: 32910944
  47. Zeng X, Su W, Liu B, Chai L, Shi R, Yao H. A review on the pharmacokinetic properties of naringin and its therapeutic efficacies in respiratory diseases. Mini Rev Med Chem 2020; 20(4): 286-93. doi: 10.2174/1389557519666191009162641 PMID: 32134369
  48. Salehi B, Fokou PVT, Sharifi-Rad M, et al. The therapeutic potential of naringenin: A review of clinical trials. Pharmaceuticals (Basel) 2019; 12(1): 11. doi: 10.3390/ph12010011 PMID: 30634637
  49. Amini N, Sarkaki A, Dianat M, Mard SA, Ahangarpour A, Badavi M. Protective effects of naringin and trimetazidine on remote effect of acute renal injury on oxidative stress and myocardial injury through Nrf-2 regulation. Pharmacol Rep 2019; 71(6): 1059-66. doi: 10.1016/j.pharep.2019.06.007 PMID: 31604166
  50. Nielsen PM, Eldirdiri A, Bertelsen LB, Jørgensen HS, Ardenkjaer-Larsen JH, Laustsen C. Fumarase activity: An in vivo and in vitro biomarker for acute kidney injury. Sci Rep 2017; 7(1): 40812. doi: 10.1038/srep40812 PMID: 28094329
  51. Chihanga T, Ma Q, Nicholson JD, et al. NMR spectroscopy and electron microscopy identification of metabolic and ultrastructural changes to the kidney following ischemia-reperfusion injury. Am J Physiol Renal Physiol 2018; 314(2): F154-66. doi: 10.1152/ajprenal.00363.2017 PMID: 28978534
  52. Shi X, Wu Y, Li E, et al. The inhibitory effects of naringin in a rat model of postoperative intraperitoneal adhesion formation. Evid Based Complement Alternat Med 2022; 2022: 1-10. doi: 10.1155/2022/5331537 PMID: 35069760
  53. Li F, Zhan Z, Qian J, Cao C, Yao W, Wang N. Naringin attenuates rat myocardial ischemia/reperfusion injury via PI3K/Akt pathway-mediated inhibition of apoptosis, oxidative stress and autophagy. Exp Ther Med 2021; 22(2): 811. doi: 10.3892/etm.2021.10243 PMID: 34131434

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers