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Introduction: Renal Ischemia/Reperfusion (I/R) causes acute kidney injury known by impaired renal function, which has partially been connected to kidney apoptosis as well as the impairment of Cyclooxygenase-2 (COX-2) and Na+/K+‐ATPase signaling. Curcuminoids have been proposed to have potential renoprotective effects. Thus, the present research work aimed to assess the effect of Nanomicellar Curcuminoids (NC) in a rat model of renal I/R.
Methods: Adult male Sprague-Dawley rats were allocated to three treatment groups (n=5/group). NC at the dose of 25 mg/kg/i.p or its vehicle was administered 60 min prior to renal ischemia induction. Then, the animals were subjected to bilateral renal ischemia for 60 min and reperfusion for 24 h. Subsequently, blood samples were collected to assess Blood Urea Nitrogen (BUN) and Creatinine (Cr) levels. In addition, kidneys were isolated to evaluate renal histopathology, caspase-3 cleavage, and COX-2 and Na+/K+ -ATPase pump levels.
Results: The results showed that NC improved kidney function (p<0.0001) and attenuated I/R-induced histopathological injuries (p<0.0001) and caspase-3 cleavage (p<0.01). However, the downregulation of renal COX-2 and Na+/K+ -ATPase expression induced by I/R was not restored by the renoprotective dose of NC.
Conclusion: The findings of the present study indicated that the renoprotective effect of NC in the renal I/R rat model coincided with the inhibition of histopathological injuries and apoptosis, but not with a compensation for renal COX-2 and Na+/K+ -ATPase downregulation.

1. Amalraj A, Pius A, Gopi S, Gopi S. Biological activities of curcuminoids, other biomolecules from turmeric and their derivatives - A review. Journal of traditional and complementary medicine 2016; 7: 205-233. [DOI:10.1016/j.jtcme.2016.05.005]
2. Amiri E, Ghasemi R, Moosavi M. Agmatine Protects Against 6-OHDA-Induced Apoptosis, and ERK and Akt/GSK Disruption in SH-SY5Y Cells. Cellular and Molecular Neurobiology 2016; 36: 829-838. [DOI:10.1007/s10571-015-0266-7]
3. Aydin M S, Caliskan A, Kocarslan A, Kocarslan S, Yildiz A, Günay S, et al. Intraperitoneal curcumin decreased lung, renal and heart injury in abdominal aorta ischemia/reperfusion model in rat. Int J Surg 2014; 12: 601-5. [DOI:10.1016/j.ijsu.2014.04.013]
4. Clausen M V, Hilbers F, Poulsen H. The Structure and Function of the Na,K-ATPase Isoforms in Health and Disease. Frontiers in physiology 2017; 8: 371-371. [DOI:10.3389/fphys.2017.00371]
5. Dawidczyk C M, Kim C, Park J H, Russell L M, Lee K H, Pomper M G, et al. State-of-the-art in design rules for drug delivery platforms: lessons learned from FDA-approved nanomedicines. Journal of Controlled Release 2014; 187: 133-144. [DOI:10.1016/j.jconrel.2014.05.036]
6. Feitoza C Q, Câmara N O, Pinheiro H S, Gonçalves G M, Cenedeze M A, Pacheco-Silva A, et al. Cyclooxygenase 1 and/or 2 blockade ameliorates the renal tissue damage triggered by ischemia and reperfusion injury. International immunopharmacology 2005; 5: 79-84. [DOI:10.1016/j.intimp.2004.09.024]
7. Féraille E, Doucet A. Sodium-potassium-adenosinetriphosphatase-dependent sodium transport in the kidney: hormonal control. Physiological reviews 2001; 81: 345-418. [DOI:10.1152/physrev.2001.81.1.345]
8. Gholampour F, Roozbeh J, Janfeshan S, Karimi Z. Remote ischemic per-conditioning protects against renal ischemia-reperfusion injury via suppressing gene expression of TLR4 and TNF-alpha in rat model. Can J Physiol Pharmacol 2019; 97: 112-119. [DOI:10.1139/cjpp-2018-0543]
9. Goetz Moro M, Vargas Sánchez P K, Lupepsa A C, Baller E M, Nobre Franco G C. Cyclooxygenase biology in renal function - literature review. Revista Colombiana de Nefrología 2017; 4: 27-37. [DOI:10.22265/acnef.4.1.263]
10. Hatamipour M, Sahebkar A, Alavizadeh S H, Dorri M, Jaafari M R. Novel nanomicelle formulation to enhance bioavailability and stability of curcuminoids. Iran J Basic Med Sci 2019; 22: 282-289.
11. Hwang H S, Yang K J, Park K C, Choi H S, Kim S H, Hong S Y, et al. Pretreatment with paricalcitol attenuates inflammation in ischemia-reperfusion injury via the up-regulation of cyclooxygenase-2 and prostaglandin E2. Nephrology Dialysis Transplantation 2013; 28: 1156-1166. [DOI:10.1093/ndt/gfs540]
12. Kar F, Hacioglu C, Senturk H, Donmez D B, Kanbak G, Uslu S. Curcumin and LOXblock-1 ameliorate ischemia-reperfusion induced inflammation and acute kidney injury by suppressing the semaphorin-plexin pathway. Life Sci 2020; 256: 118016. [DOI:10.1016/j.lfs.2020.118016]
13. Karahan M A, Yalcin S, Aydogan H, Büyükfirat E, Kücük A, Kocarslan S, et al. Curcumin and dexmedetomidine prevents oxidative stress and renal injury in hind limb ischemia/reperfusion injury in a rat model. Renal Failure 2016; 38: 693-698. [DOI:10.3109/0886022X.2016.1157746]
14. Karimi Z, SoukhakLari R, Rahimi-Jaberi K, Esmaili Z, Moosavi M. Nanomicellar curcuminoids attenuates renal ischemia/reperfusion injury in rat through prevention of apoptosis and downregulation of MAPKs pathways. Mol Biol Rep 2021; 48: 1735-1743. [DOI:10.1007/s11033-021-06214-2]
15. Kaur A, Kaur T, Singh B, Pathak D, Singh Buttar H, Pal Singh A. Curcumin alleviates ischemia reperfusion-induced acute kidney injury through NMDA receptor antagonism in rats. Ren Fail 2016; 38: 1462-1467. [DOI:10.1080/0886022X.2016.1214892]
16. Liu F, Ni W, Zhang J, Wang G, Li F, Ren W. Administration of Curcumin Protects Kidney Tubules Against Renal Ischemia-Reperfusion Injury (RIRI) by Modulating Nitric Oxide (NO) Signaling Pathway. Cell Physiol Biochem 2017; 44: 401-411. [DOI:10.1159/000484920]
17. Liu F H, Ni W J, Wang G K, Zhang J J. Protective role of curcumin on renal ischemia reperfusion injury via attenuating the inflammatory mediators and Caspase-3. Cell Mol Biol (Noisy-le-grand) 2016a; 62: 95-99.
18. Liu W, Zhai Y, Heng X, Che F Y, Chen W, Sun D, et al. Oral bioavailability of curcumin: problems and advancements. Journal of drug targeting 2016b; 24: 694-702. [DOI:10.3109/1061186X.2016.1157883]
19. Lugo-Baruqui J A, Ayyathurai R, Sriram A, Pragatheeshwar K D. Use of Mannitol for Ischemia Reperfusion Injury in Kidney Transplant and Partial Nephrectomies-Review of Literature. Current Urology Reports 2019; 20: 6. [DOI:10.1007/s11934-019-0868-6]
20. Malek M, Nematbakhsh M. Renal ischemia/reperfusion injury; from pathophysiology to treatment. Journal of renal injury prevention 2015; 4: 20-27.
21. Matsuzaki T, Watanabe H, Yoshitome K, Morisaki T, Hamada A, Nonoguchi H, et al. Downregulation of organic anion transporters in rat kidney under ischemia/reperfusion-induced acute [corrected] renal failure. Kidney Int 2007; 71: 539-47. [DOI:10.1038/]
22. McComb S, Chan P K, Guinot A, Hartmannsdottir H, Jenni S, Dobay M P, et al. Efficient apoptosis requires feedback amplification of upstream apoptotic signals by effector caspase-3 or -7. Sci Adv 2019; 5: eaau9433. [DOI:10.1126/sciadv.aau9433]
23. Moosavi M, Abbasi L, Zarifkar A, Rastegar K. The role of nitric oxide in spatial memory stages, hippocampal ERK and CaMKII phosphorylation. Pharmacol Biochem Behav 2014; 122: 164-72. [DOI:10.1016/j.pbb.2014.03.021]
24. Najafi H, Changizi Ashtiyani S, Sayedzadeh S A, Mohamadi Yarijani Z, Fakhri S. Therapeutic effects of curcumin on the functional disturbances and oxidative stress induced by renal ischemia/reperfusion in rats. Avicenna J Phytomed 2015; 5: 576-86.
25. Nørregaard R, Kwon T-H, Frøkiær J. Physiology and pathophysiology of cyclooxygenase-2 and prostaglandin E2 in the kidney. Kidney Research and Clinical Practice 2015; 34: 194-200. [DOI:10.1016/j.krcp.2015.10.004]
26. Patel N S, Cuzzocrea S, Collino M, Chaterjee P K, Mazzon E, Britti D, et al. The role of cycloxygenase-2 in the rodent kidney following ischaemia/reperfusion injury in vivo. European journal of pharmacology 2007; 562: 148-154. [DOI:10.1016/j.ejphar.2007.01.079]
27. Prasad S, Tyagi A K, Aggarwal B B. Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice. Cancer research and treatment : official journal of Korean Cancer Association 2014; 46: 2-18. [DOI:10.4143/crt.2014.46.1.2]
28. Sampaio L S, Iannotti F A, Veneziani L, Borelli-Tôrres R T, De Maio F, Piscitelli F, et al. Experimental ischemia/reperfusion model impairs endocannabinoid signaling and Na+/K+ ATPase expression and activity in kidney proximal tubule cells. Biochemical Pharmacology 2018; 154: 482-491. [DOI:10.1016/j.bcp.2018.06.005]
29. Shiva N, Sharma N, Kulkarni Y A, Mulay S R, Gaikwad A B. Renal ischemia/reperfusion injury: An insight on in vitro and in vivo models. Life Sciences 2020: 117860. [DOI:10.1016/j.lfs.2020.117860]
30. Soares R O S, Losada D M, Jordani M C, Évora P, Castro-E-Silva O. Ischemia/Reperfusion Injury Revisited: An Overview of the Latest Pharmacological Strategies. International journal of molecular sciences 2019; 20: 5034. [DOI:10.3390/ijms20205034]
31. Suleyman B, Albayrak A, Kurt N, Demirci E, Gundogdu C, Aksoy M. The effect of etoricoxib on kidney ischemia-reperfusion injury in rats: A biochemical and immunohistochemical assessment. International immunopharmacology 2014; 23: 179-185. [DOI:10.1016/j.intimp.2014.06.042]
32. Suleyman Z, Sener E, Kurt N, Comez M, Yapanoglu T. The effect of nimesulide on oxidative damage inflicted by ischemia-reperfusion on the rat renal tissue. Renal failure 2015; 37: 323-331. [DOI:10.3109/0886022X.2014.985996]
33. Villanueva S, Céspedes C, González A A, Vio C P, Velarde V. Effect of ischemic acute renal damage on the expression of COX-2 and oxidative stress-related elements in rat kidney. American Journal of Physiology-Renal Physiology 2007; 292: F1364-F1371. [DOI:10.1152/ajprenal.00344.2006]
34. Williams H D, Trevaskis N L, Charman S A, Shanker R M, Charman W N, Pouton C W, et al. Strategies to address low drug solubility in discovery and development. Pharmacol Rev 2013; 65: 315-499. [DOI:10.1124/pr.112.005660]
35. Wright J, Healy T, Balfour T, Hardcastle J. Effects of inhalation anaesthetic agents on the electrical and mechanical activity of the rat duodenum. British journal of anaesthesia 1982; 54: 1223-1230. [DOI:10.1093/bja/54.11.1223]
36. Xu Y, Hu N, Jiang W, Yuan H F, Zheng D H. Curcumin-carrying nanoparticles prevent ischemia-reperfusion injury in human renal cells. Oncotarget 2016; 7: 87390-87401. [DOI:10.18632/oncotarget.13626]
37. Yang B, Lan S, Dieudé M, Sabo-Vatasescu J-P, Karakeussian-Rimbaud A, Turgeon J, et al. Caspase-3 Is a Pivotal Regulator of Microvascular Rarefaction and Renal Fibrosis after Ischemia-Reperfusion Injury. Journal of the American Society of Nephrology : JASN 2018; 29: 1900-1916. [DOI:10.1681/ASN.2017050581]
38. Zhang J, Tang L, Li G S. The anti-inflammatory effects of curcumin on renal ischemia-reperfusion injury in rats. 2018; 40: 680-686. [DOI:10.1080/0886022X.2018.1544565]

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