Reno-protective Effects of Brusatol Against Renal Ischemia Reperfusion Injury

Yıl 2023, Cilt: 9 Sayı: 2, 136 - 141, 01.05.2023

Fazile Nur Ekinci Akdemir Ayhan Tanyeli Ersen Eraslan Mustafa Can Güler Ömer Topdağı Tuncer Nacar

https://doi.org/10.53394/akd.1027038

Öz

Purpose: The aim of this study was to determine the potential beneficial effects of brusatol treatment on oxidative kidney injury induced by bilateral renal ischemia reperfusion (RIR) method.
Material and Method: In the existing study, experimental animals were randomly assigned to 4 groups as sham, renal ischemia reperfusion (RIR), DMSO and brusatol groups. Sham group; the back region was opened by incision and then sutured but no ischemia reperfusion (IR) model was established. In RIR group, 1 hour of ischemia following 24 hours of reperfusion was formed. In DMSO group, 0,3 ml, 1% DMSO was administered intraperitoneally for each rat once in two 2 days for 10 days and a last dose was applied 30 minutes before reperfusion. Then IR model was carried out as told in RIR group. In brusatol group, brusatol was applied intraperitoneally as 0,5 mg/ml for each rat every second days for 10 days before the experiment. The last dose was administered 30 minutes before reperfusion and IR was fulfilled as depicted in RIR group. Following reperfusion period, rats were immolated and renal tissues were isolated.
Results: TNF-α, MDA and IL-1β levels, OSI, TOS and MPO values were significantly raised but TAS and SOD levels were declined in RIR and DMSO groups compared to sham group. On the other side, TAS and SOD increased while OSI and TOS values, activity of MPO and TNF-α, MDA and IL-1β levels were significantly reduced in brusatol+I/R group due to brusatol therapy compared to sham and DMSO groups.
Conclusion: Consequently, brusatol demonstrated protective effects against RIR induced oxidative kidney injury in rats.

Anahtar Kelimeler

Brusatol, Renal Ischemia Reperfusion, Oxidative stress, Rat.

Destekleyen Kurum

-

Proje Numarası

-

Teşekkür

-

Brusatol'ün Renal İskemi Reperfüzyon Hasarına Karşı Renoprotektif Etkileri

Öz

Amaç: Bu çalışmanın amacı brusatol tedavisinin bilateral renal iskemi reperfüzyon (RIR) yöntemi ile indüklenen oksidatif böbrek hasarı üzerindeki potansiyel yararlı etkilerini belirlemektir.
Gereç ve Yöntem: Mevcut çalışmada, deney hayvanları rastgele sham, renal iskemi reperfüzyonu (RIR), DMSO ve brusatol grupları olarak 4 gruba ayrıldı. Sham grubu; arka bölge insizyon ile açıldı ve sonra sütüre edildi ancak iskemi reperfüzyon (IR) modeli oluşturulmadı. RIR grubunda 24 saatlik reperfüzyonu takiben 1 saatlik iskemi oluştu. DMSO grubunda, 10 gün boyunca iki günde bir kez her sıçan için 0,3 ml %1 DMSO intraperitonal olarak uygulandı ve reperfüzyondan 30 dakika önce son bir doz uygulandı. Daha sonra RIR grubunda anlatıldığı gibi IR modeli uygulandı. Brusatol grubunda brusatol, deneyden önce 10 gün boyunca her bir sıçan için 0,5 mg/ml olarak intraperitonal olarak uygulandı. Son doz reperfüzyondan 30 dakika önce uygulandı ve IR, RIR grubunda gösterildiği gibi gerçekleştirildi. Reperfüzyon döneminden sonra sıçanlar hareketsiz hale getirildi ve böbrek dokuları izole edildi.
Bulgular: TNF-a, MDA ve IL-1β düzeyleri, OSI, TOS ve MPO değerleri anlamlı olarak yükselmiş, ancak TAS ve SOD düzeyleri sham grubuna göre RIR ve DMSO gruplarında azalmıştır. Öte yandan TAS ve SOD artarken OSI ve TOS değerleri, MPO ve TNF-α, MDA ve IL-1β düzeylerinin brusatol + I/R grubunda sham ve DMSO gruplarına göre brusatol tedavisine bağlı olarak anlamlı düzeyde azaldığı görülmüştür.
Sonuç: Sonuç olarak, brusatol sıçanlarda RIR kaynaklı oksidatif böbrek hasarına karşı koruyucu etkiler göstermiştir.

Anahtar Kelimeler

Brusatol, Renal İskemi Reperfüzyonu, Oksidatif stres, Sıçan.

Proje Numarası

-

Kaynakça

• 1. Han SJ, Noh MR, Jung JM, Ishii I, Yoo J, Kim JI, Park KM. Hydrogen sulfide-producing cystathionine gamma-lyase is critical in the progression of kidney fibrosis. Free Rad Biol Med. 2017;112:423-32
• 2. Zuk A, Bonventre JV. Acute Kidney Injury. Ann Rev Med. 2016;67:293-307
• 3. Lameire NH, Bagga A, Cruz D, De Maeseneer J, Endre Z, Kellum JA, Liu KD, Mehta RL, Pannu N, Biesen WV, Vanholder R. Acute kidney injury: an increasing global concern. Lancet 2013;382:170-9
• 4. Makris K, Spanou L. Acute kidney injury: definition, pathophysiology and clinical phenotypes. The Clinical Biochemist. Reviews. 2016;37:85-98.
• 5. Kunzendorf U, Haase M, Rolver L, Haase-Fielitz A. Novel aspects of pharmacological therapies for acute renal failure. Drugs 2010; 70:1099-114
• 6. Venkatachalam MA, Weinberg JM, Kriz W, Bidani AK. Failed Tubule Recovery, AKI-CKD Transition, and Kidney Disease Progression. J Soci Nephrol. 2015;26:1765-76
• 7. Xie Y, Xiao J, Fu C, Zhang Z, Ye Z, Zhang X. Ischemic Preconditioning promotes autophagy and alleviates renal ischemia/reperfusion injury. BioMed Res Int. 2018;8353987
• 8. Nath KA, Norby SM. Reactive oxygen species and acute renal failure. Am J Med. 2000;109:665-78
• 9. Bonventre JV, Yang L. Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest. 2011;121:4210-21
• 10. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38:1103-11
• 11. Jang HS, Kim J, Park YK, Park KM. Infiltrated macrophages contribute to recovery after ischemic injury but not to ischemic preconditioning in kidneys. Transplant. 2008;85:447-55
• 12. Yasar M, Erdi I, Kaya B. The preventive effects of atorvastatin and N-acetyl cysteine in experimentally induced ischemia-reperfusion injury in rats. Bratis Med J. 2018;119:167-74
• 13. Wu SH, Chen XQ, Lu J, Wang MJ. BML-111 attenuates renal ischemia/reperfusion injury via peroxisome proliferator-activated receptor-alpha-regulated heme oxygenase-1. Inflammation. 2016;39:611-24
• 14. Leonard MO, Kieran NE, Howell K, Burne MJ, Varadarajan R, Dhakshinamoorthy S, Porter AG, O'Farrelly C, Rabb H, Taylor CT. Reoxygenation-specific activation of the antioxidant transcription factor Nrf2 mediates cytoprotective gene expression in ischemia-reperfusion injury. FASEB J. 2006;20:2624-6
• 15. Liu JH, Qin JJ, Jin HZ, Hu XJ, Chen M, Shen YH, Yan SK, Zhang WD. A new triterpenoid from Brucea javanica. Arc Pharm Res. 2009;32:661-6
• 16. Tang W, Xie J, Xu S, Lv H, Lin M, Yuan S, Bai J, Hou Q, Yu S. Novel nitric oxide-releasing derivatives of brusatol as anti-inflammatory agents: design, synthesis, biological evaluation, and nitric oxide release studies. J Med Chem. 2014;57(18):7600-12
• 17. Ekinci Akdemir FN, Yildirim S, Kandemir FM, Tanyeli A, Küçükler S, Bahaeddin Dortbudak M. Protective effects of gallic acid on doxorubicin-induced cardiotoxicity; an experimantal study. Arch Physiol Biochem. 2019;1-8
• 18. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal-tissues by thiobarbituric acid reaction. Anal Biochem. 1979; 95:351-8
• 19. Sun Y, Oberley LW, Li Y. A Simple Method for Clinical Assay of Superoxide-Dismutase. Clin Chem. 1988;34:497-500
• 20. Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol. 1982;78:206-9
• 21. Boozari M, Hosseinzadeh H. Natural medicines for acute renal failure: A review. Phytother Res. 2017;31:1824-35
• 22. Sandal S, Bansal P, Cantarovich M. The evidence and rationale for the perioperative use of loop diuretics during kidney transplantation: A comprehensive review. Transplant Rev (Orlando). 2018;32:92-101
• 23. Wang F, Yu G, Liu SY, Li JB, Wang JF, Bo LL, Qian LR, Sun XJ, Deng XM. Hydrogen-rich saline protects against renal ischemia/reperfusion injury in rats. J Surg Res. 2011;167:339-44
• 24. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol. 2012;298:229-317
• 25. Bonventre JV. Mechanisms of ischemic acute renal failure. Kidney international. 1993;43:1160-78
• 26. Yazici A, Aksit H, Sari ES, Yay A, Erken HA, Akşit D, Cakmak H, Seyrek K, Ermiş SS. Comparison of pre-treatment and post-treatment use of selenium in retinal ischemia reperfusion injury. Int J Ophthal. 2015;8:263-8
• 27. Yang L, Brooks CR, Xiao S, Sabbisetti V, Yeung MY, Hsiao LL, Ichimura T, Kuchroo V, Bonventre JV. KIM-1-mediated phagocytosis reduces acute injury to the kidney. J Clin Invest. 2015;125:1620-36
• 28. Bolisetty S, Agarwal A. Neutrophils in acute kidney injury: not neutral any more. Kidney Int. 2009;75:674-6
• 29. Chatterjee PK, Cuzzocrea S, Brown PA, Zacharowski K, Stewart KN, Mota-Filipe H, Thiemermann C. Tempol, a membrane-permeable radical scavenger, reduces oxidant stress-mediated renal dysfunction and injury in the rat. Kidney Int. 2000;58:658-73
• 30. Rauch J, Kolch W, Laurent S, Mahmoudi M. Big signals from small particles: regulation of cell signaling pathways by nanoparticles. Chem Rev. 2013;113:3391-406
• 31. Warren JS. Interleukins and tumor necrosis factor in inflammation. Crit Rev Clin Lab Sci. 1990;28:37-59
• 32. Nawroth PP, Stern DM. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med. 1986;163:740-5
• 33. Soares BL, Freitas MA, Montero EF, Pitta GB, Fausto Miranda Jr. Alprostadil attenuates inflammatory aspects and leucocytes adhesion on renal ischemia and reperfusion injury in rats. Acta Cir Bras. 2014;29(2):55-60
• 34. Kline J, Rachoin JS. Acute kidney injury and chronic kidney disease: it's a two-way street. Ren Fail. 2013;35:452-5
• 35. Liu X, Xu H, Zhang Y, Wang P, Gao W. Brusatol inhibits amyloid-beta-induced neurotoxicity in U-251 cells via regulating the Nrf2/HO-1 pathway. J Cel Biochem. 2019;120:10556-63
• 36. Turpaev K, Krizhanovskii C, Wang X, Sargsyan E, Bergsten P, Welsh N. The protein synthesis inhibitor brusatol normalizes high-fat diet-induced glucose intolerance in male C57BL/6 mice: role of translation factor eIF5A hypusination. FASEB J. 2019;33:3510-22
• 37. Zhou J, Wang T, Dou Y, Huang Y, Qu C, , Xie Y, Huang P, Lin Z, Su Z. Brusatol ameliorates 2, 4, 6-trinitrobenzenesulfonic acid-induced experimental colitis in rats: Involvement of NF-kappaB pathway and NLRP3 inflammasome. Int Immunopharmacol. 2018;64:264-74