Protective effect of naringin in rat model of renal ischemia reperfusion injury

Mutlu Deger Department of Urology, Faculty of Medicine, Cukurova University, Adana, Turkey
Nebil Akdogan Department of Urology, Faculty of Medicine, Cukurova University, Adana, Turkey
Volkan Izol Department of Urology, Faculty of Medicine, Cukurova University, Adana, Turkey
Halil Mahir Kaplan Department of Pharmacology, Faculty of Medicine, Cukurova University, Adana, Turkey
Perçin Pazarci Department of Medical Biology, Faculty of Medicine, Cukurova University, Adana, Turkey
Ibrahim Atilla Arıdogan Department of Urology, Faculty of Medicine, Cukurova University, Adana, Turkey

Keywords: renal ischaemia reperfusion injury; naringin; inflammation; apoptosis

Abstract

Objective: We aimed to research that naringin whether protects from renal ischemia/reperfusion induced renal damage in rats. Methods: Twenty-four Wistar albino female rats randomly were divided into three groups: 1) control group, in which the rats were only performed right nephrectomy; 2) a second group received right nephrectomy and left kidney ischemia (1 h) and reperfusion (24 h) group ischemia/reperfusion (I/R); 3) a third group received 50 mg/kg naringin orally once a day for two weeks before ischemia/reperfusion (I/R/N). Expression of cyclooxygenase-2 (COX-2), cytosolic phospholipase A₂ (cPLA2), inducible nitric oxide synthase (iNOS), caspase-3, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated x protein (Bax), serum creatinine (Cr), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) were measured by using enzyme-linked immunosorbent assay (ELISA). Results: Naringin-treated rats that performed renal ischemia/reperfusion demonstrated significant decrease in Cr, IL-6 and TNF-α levels when compared to the only renal ischemia/reperfusion performed rats. While renal ischemia/reperfusion caused a decrease of bcl-2 (1.72 ± 0.20 pg/ml) levels, while an increase of COX-2 (11882 ± 642 pg/ml), cPLA2 (2448 ± 139 pg/ml), iNOS (4331 ± 438 IU/ml), cleaved caspase-3 (7.33 ± 0.76 ng/ml) and Bax (2.33 ± 0.44 ng/ml) levels. The treatment of naringin reversed these kidney effects (7.47 ± 60.35 pg/ml; 9299 ± 327 pg/ml; 2001 ± 78 pg/ml; 3112 ± 220 IU/ml; 3.38 ± 0.54 ng/ml; 2.33 ± 0.44 ng/ml, respectively) (p <0.05). Conclusion: This study showed that naringin treatment attenuated renal damage induced by ischemia/reperfusion in rats.

References

1) Nuransoy A, Beytur A, Polat A, Samdanci E, Sagir M, Parlakpinar H. Protective effect of sitagliptin against renal ischemia reperfusion injury in rats. Ren Fail. 2015;37(4):687-93. doi: 10.3109/0886022X.2015.1010991.

2) Yamamoto S, Hagiwara S, Hidaka S, Shingu C, Goto K, Kashima K, et al. The antioxidant EPC-K1 attenuates renal ischemia-reperfusion injury in a rat model. Am J Nephrol. 2011;33(6):485-90. doi: 10.1159/000327820.

3) Akçetin Z, Busch A, Kessler G, Heynemann H, Holtz J, Brömme HJ. Evidence for only a moderate lipid peroxidation during ischemia-reperfusion of rat kidney due to its high antioxidative capacity. Urol Res. 1999;27(4):280-4. doi: 10.1007/s002400050124.

4) Paller MS. Acute renal failure: controversies, clinical trials, and future directions. Semin Nephrol. 1998 Sep;18(5):482-9.

5) Reiter RJ, Guerrero JM, Garcia JJ, Acuña-Castroviejo D. Reactive oxygen intermediates, molecular damage, and aging. Relation to melatonin. Ann N Y Acad Sci. 1998;854:410-24. doi: 10.1111/j.1749-6632.1998.tb09920.x.

6) Lindsay TF, Liauw S, Romaschin AD, Walker PM. The effect of ischemia/reperfusion on adenine nucleotide metabolism and xanthine oxidase production in skeletal muscle. J Vasc Surg. 1990;12(1):8-15. doi: 10.1067/mva.1990.19946.

7) Chamoun F, Burne M, O'Donnell M, Rabb H. Pathophysiologic role of selectins and their ligands in ischemia reperfusion injury. Front Biosci. 2000;5:E103-9. doi: 10.2741/chamoun.

8) Cruz CM, Rinna A, Forman HJ, Ventura AL, Persechini PM, Ojcius DM. ATP activates a reactive oxygen species-dependent oxidative stress response and secretion of proinflammatory cytokines in macrophages. J Biol Chem. 2007;282(5):2871-9. doi: 10.1074/jbc.M608083200.

9) Beutler B. Neo-ligands for innate immune receptors and the etiology of sterile inflammatory disease. Immunol Rev. 2007;220:113-28. doi: 10.1111/j.1600-065X.2007.00577.x.

10) Chatterjee PK, Patel NS, Sivarajah A, Kvale EO, Dugo L, Cuzzocrea S, et al. GW274150, a potent and highly selective inhibitor of iNOS, reduces experimental renal ischemia/reperfusion injury. Kidney Int. 2003;63(3):853-65. doi: 10.1046/j.1523-1755.2003.00802.x.

11) Bharti S, Rani N, Krishnamurthy B, Arya DS. Preclinical evidence for the pharmacological actions of naringin: a review. Planta Med. 2014;80(6):437-51. doi: 10.1055/s-0034-1368351.

12) Zeng L, Zhen Y, Chen Y, Zou L, Zhang Y, Hu F, et al. Naringin inhibits growth and induces apoptosis by a mechanism dependent on reduced activation of NF‑κB/COX‑2‑caspase-1 pathway in HeLa cervical cancer cells. Int J Oncol. 2014;45(5):1929-36. doi: 10.3892/ijo.2014.2617.

13) Gutiérrez-Venegas G, Ventura-Arroyo JA, Arreguín-Cano JA, Ostoa-Pérez MF. Flavonoids inhibit iNOS production via mitogen activated proteins in lipoteichoic acid stimulated cardiomyoblasts. Int Immunopharmacol. 2014;21(2):320-7. doi: 10.1016/j.intimp.2014.04.010.

14) Hamada T, Tsuchihashi S, Avanesyan A, Duarte S, Moore C, Busuttil RW, et al. Cyclooxygenase-2 deficiency enhances Th2 immune responses and impairs neutrophil recruitment in hepatic ischemia/reperfusion injury. J Immunol. 2008;180(3):1843-53. doi: 10.4049/jimmunol.180.3.1843.

15) Williams P, López H, Britt D, Chan C, Ezrin A, Hottendorf R. Characterization of renal ischemia-reperfusion injury in rats. J Pharmacol Toxicol Methods. 1997;37(1):1-7. doi: 10.1016/s1056-8719(96)00141-4.

16) Carrier D, Bou Khalil M, Kealey A. Modulation of phospholipase A2 activity by aminoglycosides and daptomycin: a Fourier transform infrared spectroscopic study. Biochemistry. 1998;37(20):7589-97. doi: 10.1021/bi971793d.

17) Hosaka EM, Santos OFP, Seguro AC, Vattimo MFF. Effect of cyclooxygenase inhibitors on gentamicin-induced nephrotoxicity in rats. Braz J Med Biol Res. 2004;37(7):979-85. doi: 10.1590/S0100-879X2004000700006.

18) Kao SJ, Lei HC, Kuo CT, Chang MS, Chen BC, Chang YC, et al. Lipoteichoic acid induces nuclear factor-kappaB activation and nitric oxide synthase expression via phosphatidylinositol 3-kinase, Akt, and p38 MAPK in RAW 264.7 macrophages. Immunology. 2005;115(3):366-74. doi: 10.1111/j.1365-2567.2005.02160.x.

19) Lien YH, Lai LW, Silva AL. Pathogenesis of renal ischemia/reperfusion injury: lessons from knockout mice. Life Sci. 2003;74(5):543-52. doi: 10.1016/j.lfs.2003.08.001.

20) Ceriello A, Falleti E, Motz E, Taboga C, Tonutti L, Ezsol Z, et al. Hyperglycemia-induced circulating ICAM-1 increase in diabetes mellitus: the possible role of oxidative stress. Horm Metab Res. 1998;30(3):146-9. doi: 10.1055/s-2007-978854.

21) Chai YC, Ashraf SS, Rokutan K, Johnston RB Jr, Thomas JA. S-thiolation of individual human neutrophil proteins including actin by stimulation of the respiratory burst: evidence against a role for glutathione disulfide. Arch Biochem Biophys. 1994;310(1):273-81. doi: 10.1006/abbi.1994.1167.

22) Kannan K, Jain SK. Oxidative stress and apoptosis. Pathophysiology. 2000;7(3):153-63. doi: 10.1016/s0928-4680(00)00053-5.

23) Cavia-Saiz M, Busto MD, Pilar-Izquierdo MC, Ortega N, Perez-Mateos M, Muñiz P. Antioxidant properties, radical scavenging activity and biomolecule protection capacity of flavonoid naringenin and its glycoside naringin: a comparative study. J Sci Food Agric. 2010;90(7):1238-44. doi: 10.1002/jsfa.3959.

24) Amini N, Sarkaki A, Dianat M, Mard SA, Ahangarpour A, Badavi M. The renoprotective effects of naringin and trimetazidine on renal ischemia/reperfusion injury in rats through inhibition of apoptosis and downregulation of micoRNA-10a. Biomed Pharmacother. 2019;112:108568. doi: 10.1016/j.biopha.2019.01.029.

25) Singh D, Chopra K. The effect of naringin, a bioflavonoid on ischemia-reperfusion induced renal injury in rats. Pharmacol Res. 2004;50(2):187-93. doi: 10.1016/j.phrs.2004.01.007.

Published

2021-06-22

How to Cite

Deger M, Akdogan N, Izol V, Kaplan HM, Pazarci P, Arıdogan IA. Protective effect of naringin in rat model of renal ischemia reperfusion injury. Rev Nefrol Dial Traspl. [Internet]. 2021Jun.22 [cited 2024May12];41(2):113-8. Available from: http://vps-1689312-x.dattaweb.com/index.php/rndt/article/view/647

Download Citation

Issue

Vol. 41 No. 2 (2021): Abr.-Jun.

Section

Original Article

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.