Nephroprotective Effect of Astaxanthin Against Radiotherapy Via TAS, TOS (Biochemical), TNF-α, CASPASE-3 (Immunohistochemical), SIRT1-P53 (Molecular) Pathway in Rats

Year 2023, , 14 - 20, 28.02.2023

Gamze Erkılınç , Mehmet Bedir , Leyla Elif Özgü Ayözger , Hatice Kübra Doğan , Nasıf Fatih Karakuyu

https://doi.org/10.54005/geneltip.1088311

Abstract

Aim: To evaluate the effects of Astaxanthin (ATX), known for its antioxidant properties, on the kidneys of rats given radiation by biochemical measuring total oxidant level (TOS), total antioxidant level (TAS), immunohistochemically by Cas3 (Cysteine Aspartate Specific ProteASEs), TNF-α (Tumor necrosis factor-alpha), and molecularly by P53, SIRT (Sirtuin -1) pathways.

Materials and Methods: The rats were divided into 4 groups (8 rats per group): control, radiotherapy (RT), RT+ATX, ATX. ATX was given to rats at 4 mg/kg for 7 days. We evaluated to effect of ATX in rats’ kidneys damaged by RT by comparing all groups with TAS, TOS, Cas 3, TNF-α, and SIRT-1, P53.
Results: TAS levels were similar among the control, RT, RT+ATX, and ATX groups. TOS levels were significantly lower in the ATX group compared to RT, Control, and RT+ATX groups. Histopathologically marked hyperemia and in some kidneys, small hemorrhages were observed in the RT group. In addition, marked glomerular sclerosis was also detected in this group. With ATX, we observed significant improvement in the RT+ATX group. Immunohistochemically revealed increased Cas3 expressions, tubular cells in TNF-α expressions in the RT group. ATX treatment decreased Cas3 and TNF-α expression in the RT+ATX group. No Cas3 and TNF-α expression was observed in both control and ATX groups. There was no significant difference between the groups in SIRT-1, P53 values.
Conclusion: Astaxanthin was observed that it is a carotenoid that may benefit the recovery of tubular and glomerular cells in kidney damage after radiation, and it has positive effects on oxidative stress.

Keywords

Radiotherapy effects, Rat kidney, Astaxanthin, Caspase 3, SIRT-1, P53, TNF-α

Supporting Institution

This study was supported by the Scientific Research Project Unit of Suleyman Demirel University

Project Number

TSG-2020-8134

Thanks

none

Astaksantin’in Sıçanlarda TAS, TOS (Biyokimyasal), TNF-α, CASPASE-3 (İmmünohistokimyasal), SIRT-1-P53 (Moleküler) Yolu Aracılığıyla Radyoterapiye Karşı Nefroprotektif Etkisi

Abstract

Amaç: Antioksidan özelliği ile bilinen Astaksantin'in (ATX) radyasyon verilen sıçanların böbrekleri üzerindeki etkilerini biyokimyasal olarak total oksidan düzeyi (TOS), total antioksidan düzeyi (TAS), Cas3 (Sistein Aspartat Spesifik ProteASE'ler), TNF-a (Tümör nekroz faktörü-alfa) ile immünohistokimyasal olarak ve P53, SIRT (Sirtuin -1) yolakları ile moleküler olarak değerlendirmek.
Gereç ve Yöntem: Sıçanlar 4 gruba ayrıldı (grup başına 8 sıçan): kontrol, radyoterapi (RT), RT+ATX, ATX. Sıçanlara 7 gün boyunca 4 mg/kg ATX verildi. RT ile hasar görmüş sıçanların böbreklerinde ATX'in etkisini tüm gruplarda TAS, TOS, Cas 3, TNF-α ve SIRT-1, P53 ile karşılaştırarak değerlendirdik.
Bulgular: TAS düzeyleri kontrol, RT, RT+ATX ve ATX grupları arasında benzerdi. TOS seviyeleri, ATX grubunda RT, Kontrol ve RT+ATX gruplarına kıyasla anlamlı derecede düşüktü. RT grubunda histopatolojik olarak belirgin hiperemi ve bazı böbreklerde küçük kanamalar gözlendi. Ayrıca bu grupta belirgin glomerüler skleroz da saptandı. ATX ile, RT+ATX grubunda belirgin şekilde iyileşme gözlemledik. İmmünohistokimyasal olarak RT grubunda Cas3 ekspresyonlarında artış, TNF-α’nın tübüler hücreler ekspresyonu saptandı. ATX tedavisi, RT+ATX grubunda Cas3 ve TNF-α ekspresyonunu azalttı. Hem kontrol hem de ATX gruplarında Cas3 ve TNF-α ekspresyonu gözlenmedi. SIRT-1, P53 değerlerinde gruplar arasında anlamlı fark yoktu.
Sonuç: Astaksantin'in radyasyon sonrası böbrek hasarında tübüler ve glomerüler hücrelerin iyileşmesine fayda sağlayabilecek bir karotenoid olduğu ve oksidatif stres üzerinde olumlu etkileri olduğu gözlendi.

Keywords

Radyoterapi etkileri, Rat böbreği, Astaksantin, Kaspaz 3, , Kaspaz 3, SIRT-1, P53, TNF-α

Project Number

TSG-2020-8134

References

• 1. Denham JW, Hauer-Jensen M. The radiotherapeutic injury–a complex ‘wound’. Radiother Oncol. 2002;63(2):129-45.
• 2. Koj A. Termination of acute-phase response: role of some cytokines and anti-inflammatory drugs. General Pharmacology: The Vascular System. 1998;31(1):9-18.
• 3. Akbulut G, Dilek ON, Kahraman A, Köken T, Serteser M. The correlation between renal tissue oxidative stress parameters and TNF-alpha levels in an experimental model of ischemia-reperfusion injury in mice. Ulusal Travma Dergisi. 2005;11(1):11-6.
• 4. Carlos CP, Sonehara NM, Oliani SM, Burdmann EA. Predictive usefulness of urinary biomarkers for the identification of cyclosporine A-induced nephrotoxicity in a rat model. PLoS One. 2014;9(7):e103660.
• 5. Tsai M-H, Cook JA, Chandramouli GV, DeGraff W, Yan H, Zhao S, et al. Gene expression profiling of breast, prostate, and glioma cells following single versus fractionated doses of radiation. Cancer Res. 2007;67(8):3845-52.
• 6. Karaman A. Mide kanserinde P53 tümör supresör geninin rolü. Türkiye Klinikleri Tıp Bilimleri Dergisi. 2003;23:67-73.
• 7. Jahan S, Munawar A, Razak S, Anam S, Ain QU, Ullah H, et al. Ameliorative effects of rutin against cisplatin-induced reproductive toxicity in male rats. BMC Urol. 2018;18(1):1-11.
• 8. Kume S, Uzu T, Horiike K, Chin-Kanasaki M, Isshiki K, Araki S-i, et al. Calorie restriction enhances cell adaptation to hypoxia through Sirt1-dependent mitochondrial autophagy in mouse aged kidney. The Journal of clinical investigation. 2010;120(4):1043-55.
• 9. Salminen A, Kaarniranta K. SIRT1: regulation of longevity via autophagy. Cell Signal. 2009;21(9):1356-60.
• 10. Donmez G, Guarente L. Aging and disease: connections to sirtuins. Aging Cell. 2010;9(2):285-90.
• 11. Hussein G, Sankawa U, Goto H, Matsumoto K, Watanabe H. Astaxanthin, a carotenoid with potential in human health and nutrition. J Nat Prod. 2006;69(3):443-9.
• 12. Higuera-Ciapara I, Felix-Valenzuela L, Goycoolea F. Astaxanthin: a review of its chemistry and applications. Crit Rev Food Sci Nutr. 2006;46(2):185-96.
• 13. Chen Y, Li D, Lu W, Xing J, Hui B, Han Y. Screening and characterization of astaxanthin-hyperproducing mutants of Haematococcus pluvialis. Biotechnol Lett. 2003;25(7):527-9.
• 14. Shibata A, Kiba Y, Akati N, Fukuzawa K, Terada H. Molecular characteristics of astaxanthin and β-carotene in the phospholipid monolayer and their distributions in the phospholipid bilayer. Chem Phys Lipids. 2001;113(1-2):11-22.
• 15. Qiu X, Fu K, Zhao X, Zhang Y, Yuan Y, Zhang S, et al. Protective effects of astaxanthin against ischemia/reperfusion induced renal injury in mice. J Transl Med. 2015;13(1):1-9.
• 16. Mentese A, Turkmen S, Karaguzel E, Karaca Y, Tatli O, Sumer AU, et al. The predictive value of ischemia-modified albumin in long-term results of ischemia-reperfusion injury in an experimental testicular torsion model. Urology. 2012;80(3):689-94.
• 17. Inborr J, Lignell Å, editors. Effect of feeding astaxanthin-rich algae meal (Haematococcus pluvialis) on performance and carotenoid concentration of different tissues of broiler chickens. Proceedings of the XIII WPSA Conference on Poultry Meat Quality in Poznan (Poland: Session M1); 1997.
• 18. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004;37(2):112-9.
• 19. Chen Q, Tao J, Xie X. Astaxanthin promotes Nrf2/ARE signaling to inhibit HG-induced renal fibrosis in GMCs. Mar Drugs. 2018;16(4):117.
• 20. Chang MX, Xiong F. Astaxanthin and its effects in inflammatory responses and inflammation-associated diseases: recent advances and future directions. Molecules. 2020;25(22):5342.
• 21. Hagen C, Grünewald K, Xyländer M, Rothe E. Effect of cultivation parameters on growth and pigment biosynthesis in flagellated cells of Haematococcus pluvialis. Journal of Applied Phycology. 2001;13(1):79-87.
• 22. Gao D, Wang H, Xu Y, Zheng D, Zhang Q, Li W. Protective effect of astaxanthin against contrast-induced acute kidney injury via SIRT1-P53 pathway in rats. Int Urol Nephrol. 2019;51(2):351-8.
• 23. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem. 2004;37(4):277-85.
• 24. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38(12):1103-11.
• 25. Kunkler P, Farr R, Luxton R. The limit of renal tolerance to X rays. The British journal of radiology. 1952;25(292):190-201.
• 26. Robbins ME, Zhao W, Davis CS, Toyokuni S, Bonsib SM. Radiation-induced kidney injury: a role for chronic oxidative stress? Micron. 2002;33(2):133-41.
• 27. Atessahin A, Yilmaz S, Karahan I, Ceribasi AO, Karaoglu A. Effects of lycopene against cisplatin-induced nephrotoxicity and oxidative stress in rats. Toxicology. 2005;212(2-3):116-23.
• 28. Abdel-Wahab WM, Moussa FI, Saad NA. Synergistic protective effect of N-acetylcysteine and taurine against cisplatin-induced nephrotoxicity in rats. Drug Des Devel Ther. 2017;11:901.
• 29. Wang X, Zhao H, Shao Y, Wang P, Wei Y, Zhang W, et al. Nephroprotective effect of astaxanthin against trivalent inorganic arsenic-induced renal injury in wistar rats. Nutr Res Pract. 2014;8(1):46-53.
• 30. Ikeuchi M, Koyama T, Takahashi J, Yazawa K. Effects of astaxanthin in obese mice fed a high-fat diet. Biosci Biotechnol Biochem. 2007;71(4):893-9.
• 31. Naito Y, Uchiyama K, Aoi W, Hasegawa G, Nakamura N, Yoshida N, et al. Prevention of diabetic nephropathy by treatment with astaxanthin in diabetic db/db mice. Biofactors. 2004;20(1):49-59.
• 32. Ghlissi Z, Hakim A, Sila A, Mnif H, Zeghal K, Rebai T, et al. Evaluation of efficacy of natural astaxanthin and vitamin E in prevention of colistin-induced nephrotoxicity in the rat model. Environ Toxicol Pharmacol. 2014;37(3):960-6.
• 33. Cermik H, Taslipinar MY, Aydin I, Agilli M, Aydin FN, Ucar F, et al. The relationship between N-acetylcysteine, hyperbaric oxygen, and inflammation in a rat model of acetaminophen-induced nephrotoxicity. Inflammation. 2013;36(5):1145-52.
• 34. Guo S-X, Zhou H-L, Huang C-L, You C-G, Fang Q, Wu P, et al. Astaxanthin attenuates early acute kidney injury following severe burns in rats by ameliorating oxidative stress and mitochondrial-related apoptosis. Mar Drugs. 2015;13(4):2105-23.
• 35. Scott SL, Earle JD, Gumerlock PH. Functional P53 increases prostate cancer cell survival after exposure to fractionated doses of ionizing radiation. Cancer Res. 2003;63(21):7190-6.
• 36. Haas-Kogan DA, Kogan SS, Yount G, Hsu J, Haas M, Deen DF, et al. P53 function influences the effect of fractionated radiotherapy on glioblastoma tumors. International Journal of Radiation Oncology* Biology* Physics. 1999;43(2):399-403.
• 37. Dahlberg WK, Azzam EI, Yu Y, Little JB. Response of human tumor cells of varying radiosensitivity and radiocurability to fractionated irradiation. Cancer Res. 1999;59(20):5365-9.