SavedAdd your journal

Journals / Etlik Veteriner Mikrobiyoloji Dergisi / 2026 / Cilt: 35 Sayı: 1

Taxifolin attenuates cisplatin-induced kidney damage in rats via suppressing p53 and iNOS

Taxifolin, p53 ve iNOS'u baskılayarak sıçanlarda sisplatin kaynaklı böbrek hasarını hafifletir.

Gökhan Akçakavak(Veteriner Fakültesi)0000-0001-5949-4752
Özhan Karataş(CUMHURIYET UNIVERSITY)0000-0002-2778-8059
Zeynep Çelik(SELCUK UNIVERSITY)0000-0002-9667-5728
Ayşenur Tural(SELCUK UNIVERSITY)0000-0003-1585-3359
Osman Dağar(SELCUK UNIVERSITY)0000-0003-2209-7512
Ahmed Abduljabbar(Department of Medical Laboratory Technology, Erbil Technical Health and Medical College, Erbil Polytechnic Univercity, Erbil 44001, Iraq)0000-0001-9689-4018
Bahadır Kılınç(Etlik Central Veterinary Control and Research Institute, Pathology Department, Ankara, 06100, Türkiye)0000-0003-3426-2116
Mehmet Tuzcu(SELÇUK ÜNİVERSİTESİ)0000-0003-3118-1054
Pages
1–7
Publication Date
2024-07-04
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Current findings revealed nephroprotective and ameliorative effects of Tax against CP-induced kidney toxicity.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Cisplatin (CP) is a platinum-based anticancer drug used to treat many different solid tumors.
📊
Key Findings & Data:This study consisted of Control (C), Taxifolin (Tax), Cisplatin (CP) and Cisplatin + Taxifolin (CP + Tax) groups, and there were 6 rats in each group.
💡
Conclusion & Impact:Current findings revealed nephroprotective and ameliorative effects of Tax against CP-induced kidney toxicity.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:histopatoloji · iNOS · taksifolin

Abstract

Cisplatin (CP) is a platinum-based anticancer drug used to treat many different solid tumors. Although CP has strong anticancer properties, its clinical use is limited due to side effects such as ototoxicity, neurotoxicity, myelosuppression and nephrotoxicity. Taxifolin (Tax) is reported to exhibit various possess effects such as anti-inflammatory, antioxidant, antimicrobial, antiviral and anticancer. In this study, we aimed to investigate the possible effects of Tax on CP-induced nephrotoxicity. This study consisted of Control (C), Taxifolin (Tax), Cisplatin (CP) and Cisplatin + Taxifolin (CP + Tax) groups, and there were 6 rats in each group. CP was administered to rats intraperitoneally (i.p.) in a single dose of 7 mg/kg, and Tax was administered orally at a dose of 50 mg/kg for 7 consecutive days. Histopathologically, significant changes such as tubular epithelial degeneration and necrosis, tubular dilatation, inflammatory cell infiltrates, hyaline cast, and glomerular atrophy were detected in the CP group. It was seen that the CP+Tax group significantly reduced histopathological changes (p<0.001). In addition, immunohistochemically, the expressions of inducible nitric oxide synthase (iNOS) and p53 were highly irregular in the CP group relative to the control groups (p<0.001). Taxifolin treatment (CP+Tax group) significantly decreased the expressions of iNOS and p53 (p<0.001). Current findings revealed nephroprotective and ameliorative effects of Tax against CP-induced kidney toxicity.

Özet

Sisplatin (SP), birçok farklı solid tümörün tedavisinde kullanılan platin bazlı bir antikanser ilaçtır. Sisplatin güçlü antikanser özelliklere sahip olmasına rağmen ototoksisite, nörotoksisite, miyelosüpresyon ve nefrotoksisite gibi yan etkileri nedeniyle klinik kullanımı sınırlıdır. Taksifolin (Tak)'in antiinflamatuar, antioksidan, antimikrobiyal, antiviral ve antikanser gibi çeşitli etkilere sahip olduğu bildirilmektedir. Bu çalışmada Tak'in SP kaynaklı nefrotoksisite üzerindeki olası etkilerinin araştırılması amaçlandı. Bu çalışma Kontrol (K), Taksifolin (Tak), Sisplatin (SP) ve Sisplatin+Taksifolin (SP+Tak) gruplarından oluştu ve her grupta 6 sıçan yer aldı. SP, sıçanlara intraperitoneal (i.p.) olarak tek doz 7 mg/kg uygulandı ve Tak, oral olarak 50 mg/kg dozunda ardışık 7 gün uygulandı. Histopatolojik olarak SP grubunda tübüler epitelyal dejenerasyon ve nekroz, tübüler dilatasyon, yangı hücre infiltrasyonu, hiyalin silindir ve glomerüler atrofi gibi önemli değişiklikler tespit edildi. SP+Tak grubunun histopatolojik değişiklikleri anlamlı düzeyde azalttığı görüldü (p<0,001). Ayrıca immünohistokimyasal olarak indüklenebilir nitrik oksit sentaz (iNOS) ve p53 ekspresyonlarının SP grubunda kontrol gruplarına göre oldukça düzensiz olduğu görüldü (p<0,001). Taksifolin tedavisi (SP+Tak grubu) iNOS ve p53 ekspresyonlarını anlamlı düzeyde azalttı (p<0.001). Mevcut bulgular, Tak'in SP kaynaklı böbrek toksisitesine karşı nefroprotektif ve iyileştirici etkileri ortaya koydu.

🔖

Cite This Article

Akçakavak, G., Karataş, Ö., Çelik, Z., Tural, A., Dağar, O., Abduljabbar, A., Kılınç, B., Tuzcu, M. (2024). Taxifolin attenuates cisplatin-induced kidney damage in rats via suppressing p53 and iNOS. Etlik Veteriner Mikrobiyoloji Dergisi, Cilt: 35 Sayı: 1, 1–7. https://doi.org/10.35864/evmd.1458328

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (48)

  1. Akcakavak G, Kazak F, Karatas O, Alakus H, Alakus I, Kirgi O, Celik Z, Yilmaz Deveci MZ, Ozdemir O, Tuzcu M. (2024) Eucalyptol regulates Nrf2 and NF-kB signaling and alleviates gentamicin-induced kidney injury in rats by downregulating oxidative stress, oxidative DNA damage, inflammation, and apoptosis. Toxicol Mech Methods, 34(4), doi: 10.1080/15376516.2023.2297234.
  2. Akcakavak G, Kazak F, Yilmaz Deveci MZ. (2023) Eucalyptol Protects against Cisplatin-Induced Liver Injury in Rats. Biol Bullet, 50(5), 987-994. doi: 10.1134/s106235902360085x
  3. Aladaileh SH, Al-Swailmi FK, Abukhalil MH, Ahmeda AF, Mahmoud AM. (2021) Punicalagin prevents cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammatory response, and apoptosis in rats. Life sci, 286, 120071. doi: 10.1016/j.lfs.2021.120071.
  4. Alanezi AA, Almuqati AF, Alfwuaire MA, Alasmari F, Namazi NI, Althunibat OY, Mahmoud AM. (2022) Taxifolin prevents cisplatin nephrotoxicity by modulating Nrf2/HO-1 pathway and mitigating oxidative stress and inflammation in mice. Pharmaceuticals, 15(11), 1310. doi: 10.3390/ph15111310.
  5. Aldemir M, Okulu, Kösemehmetoğlu K, Ener, Topal F, Evirgen O, Gürleyik E, Avcı A. (2014) Evaluation of the protective effect of quercetin against cisplatin‐induced renal and testis tissue damage and sperm parameters in rats. Andrologia, 46(10), 1089-1097. doi: 10.1111/and.12197.
  6. Althunibat OY, Abukhalil MH, Jghef MM, Alfwuaires MA, Algefare AI, Alsuwayt B, Alazragi R, Abourehab MA, Almuqati AF, Karimulla S. (2023). Hepatoprotective effect of taxifolin on cyclophosphamide-induced oxidative stress, inflammation, and apoptosis in mice: Involvement of Nrf2/HO-1 signaling. Biomol Biomed, 23(4), 649. doi: 10.17305/bb.2022.8743.
  7. Bassett EA, Wang W, Rastinejad F, El-Deiry WS. (2008) Structural and functional basis for therapeutic modulation of p53 signaling. Clin cancer res, 14(20), 6376-6386. doi: 10.1158/1078-0432.CCR-08-1526.
  8. Ben Ayed W, Ben Said A, Hamdi A, Mokrani A, Masmoudi Y, Toukabri I, Limayem I, Yahyaoui Y. (2020) Toxicity, risk factors and management of cisplatin-induced toxicity: A prospective study. J Oncol Pharm Pract, 26(7), 1621-1629. https://doi.org/10.1177/1078155219901305
  9. Chirino YI, Trujillo J, Sánchez-González DJ, Martínez-Martínez CM, Cruz C, Bobadilla NA, Pedraza-Chaverri J. (2008) Selective iNOS inhibition reduces renal damage induced by cisplatin. Toxicol let, 176(1), 48-57. Dasari S, Tchounwou PB. (2014) Cisplatin in cancer therapy: molecular mechanisms of action. European J Pharm, 740, 364-378. doi: 10.1016/j.ejphar.2014.07.025.
  10. Erhan E, Salcan I, Dilber M, GÜRSUL C, Yilmaz K., Çoban, TA, Cimen FK, Suleyman H. (2021) Taxifolinin sıçanlarda amikasin ile indüklenen ototoksisiteye karşı koruyucu etkisi: Biyokimyasal ve histopatolojik değerlendirme. Kafkas J Med Sci, 11(2), 318-323.
  11. Ersoy A, Yaşar H, Tanoğlu C, Yazici G, Çoban T, Arslan Y, Süleyman H. (2021) The Effect of Taxifolin on Acrylamide-induced Oxidative and Proinflammatory Brain Injury in Rats: A Biochemical and Histopathological Study. Indian J Pharml Edu Res, 55(3s). doi: 10.5530/ijper.55.3s.183
  12. Geyikoglu F, Emir M, Colak S, Koc K, Turkez H, Bakir M, Hosseinigouzdagani M, Cerig S, Keles ON, Ozek NS. (2017) Effect of oleuropein against chemotherapy drug-induced histological changes, oxidative stress, and DNA damages in rat kidney injury. J Food Drug Anal, 25(2), 447-459. doi: 10.1016/j.jfda.2016.07.002.
  13. Halliwell B. (2006) Reactive species and antioxidants. Redox biology is a fundamental theme of aerobic life. Plant physiol, 141(2), 312-322. doi: 10.1104/pp.106.077073.
  14. Jain S, Vaidya A. (2023) Comprehensive review on pharmacological effects and mechanism of actions of taxifolin: A bioactive flavonoid. Pharmacol Res Mod Chin Med, p.100240.
  15. Kara AV, Aldemir MN, Ozcicek F, Mammadov R, Yazici GN, Sunar M, Gulaboglu M (2019). Protective effect of taxifolin on cisplatin-induced nephrotoxicity in rats. Anal Quant Cytopathol Histopathol, 41, 47-54. doi: 10.3390/ph15111310
  16. Kazak F, Deveci MZY, Akçakavak G. (2022) Eucalyptol alleviates cisplatin-induced kidney damage in rats. Drug and chemical toxicology, 47(2), 172-179 doi: 10.1080/01480545.2022.2156530.
  17. Kurutas EB. (2015). The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr J, 15, 1-22. doi: 10.1186/s12937-016-0186-5.
  18. Le X, Hanna EY. (2018) Optimal regimen of cisplatin in squamous cell carcinoma of head and neck yet to be determined. Ann Transl Med, 6(11), 229. doi: 10.21037/atm.2018.05.10.
  19. Levine AJ, Oren M. (2009). The first 30 years of p53: growing ever more complex. Nat rev cancer, 9(10), 749-758. doi: 10.1038/nrc2723.
  20. Liu Z, Jia J, Chen F, Yang F, Zu Y, Yang L. (2014). Development of an ionic liquid-based microwave-assisted method for the extraction and determination of taxifolin in different parts of Larix gmelinii. Molecules, 19(12), 19471-19490. doi: 10.3390/molecules191219471
  21. McSweeney KR, Gadanec LK, Qaradakhi T, Ali BA, Zulli A, Apostolopoulos V. (2021). Mechanisms of cisplatin-induced acute kidney injury: pathological mechanisms, pharmacological interventions, and genetic mitigations. Cancers, 13(7), 1572. doi: 10.3390/cancers13071572
  22. Mercantepe F, Mercantepe T, Topcu A, Yılmaz A, Tumkaya L. (2018) Protective effects of amifostine, curcumin, and melatonin against cisplatin-induced acute kidney injury. Naunyn-Schmiedeberg's Arch Pharmacol, 391, 915-931. doi: 10.1007/s00210-018-1514-4.
  23. Molitoris BA, Dagher PC, Sandoval RM, Campos SB, Ashush H, Fridman E, Brafman A, Faerman A, Atkinson SJ, Thompson JD. (2009) siRNA targeted to p53 attenuates ischemic and cisplatin-induced acute kidney injury. J Am Soc of Nephrol, 20(8), 1754-1764. doi: 10.1681/ASN.2008111204
  24. Morsy MA, Ibrahim SA, Amin EF, Kamel MY, Rifaai RA, Hassan MK. (2014). Sildenafil ameliorates gentamicin-induced nephrotoxicity in rats: role of iNOS and eNOS. J Toxicol, 2014, 489382 doi: 10.1155/2014/489382.
  25. Obeidat HM, Althunibat OY, Alfwuaires MA, Aladaileh SH, Algefare AI, Almuqati AF, Alasmari F, Aldal’in HK, Alanezi AA, Alsuwayt B. (2022).
  26. Cardioprotective effect of taxifolin against isoproterenol-induced cardiac injury through decreasing oxidative stress, inflammation, and cell death, and activating Nrf2/HO-1 in mice. Biomolecules, 12(11), 1546. doi: 10.3390/biom12111546.
  27. Okkay U, Ferah Okkay I, Cicek B, Aydin IC, Ozkaraca M (2022). Hepatoprotective and neuroprotective effect of taxifolin on hepatic encephalopathy in rats. Metab Brain Dis, 37(5), 1541-1556. Doi: 10.1007/s11011-022-00952-3
  28. Ölmeztürk Karakurt TC, Eren N, Subaşı F, Kuyrukluyıldız U, Çoban TA, Süleyman H, Mokhtare B. (2023). Effects of taxifolin on tramadol-induced oxidative and inflammatory liver injury in rats: an experimental study. Drug and chem toxicol, 1-6.
  29. Pan H, Mukhopadhyay P, Rajesh M, Patel V, Mukhopadhyay B, Gao B, Haskó G, Pacher P. (2009) Cannabidiol attenuates cisplatin-induced nephrotoxicity by decreasing oxidative/nitrosative stress, inflammation, and cell death. J Pharmacol Exp Ther, 328(3), 708-714. doi: 10.1124/jpet.108.147181.
  30. Sabapathy K, Lane DP. (2018) Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others. Nature Rev Clin Oncol, 15(1), 13-30. doi: 10.1038/nrclinonc.2017.151.
  31. Simovic Markovic B, Gazdic M, Arsenijevic A, Jovicic N, Jeremic J, Djonov V, Arsenijevic N, Lukic ML, Volarevic V. (2017) Mesenchymal stem cells attenuate cisplatin-induced nephrotoxicity in iNOS-dependent manner. Stem cells int, 2017, 1315378 doi: 10.1155/2017/1315378.
  32. Skinner R, Pearson, English M, Price L, Wyllie R, Coulthard M, Craft A. (1998) Cisplatin dose rate as a risk factor for nephrotoxicity in children. British J Cancer, 77(10), 1677-1682. doi: 10.1038/bjc.1998.276.
  33. Tang C, Ma Z, Zhu J, Liu Z, Liu Y, Liu Y, Cai J, Dong Z. (2019) P53 in kidney injury and repair: mechanism and therapeutic potentials. Pharmacol Ther, 195, 5-12. doi: 10.1016/j.pharmthera.2018.10.013.
  34. Topal I, Özdamar MY, Catakli T, Malkoc İ, Hacimuftuoglu A, Mamoulakis C, Tsatsakis A, Tsarouhas K, Tsitsimpikou C, Taghizadehghalehjoughi A. (2023). Renoprotective effect of taxifolin in paracetamol-induced nephrotoxicity: emerging evidence from an animal model. J Clin Med, 12(3), 876. doi: 10.3390/jcm12030876.
  35. Tuñón MAJ, Sánchez-Campos S, Gutiérrez B, Culebras JM, González-Gallego J. (2003) Effects of FK506 and rapamycin on generation of reactive oxygen species, nitric oxide production and nuclear factor kappa B activation in rat hepatocytes. Biochem Pharmaco, 66(3), 439-445. doi: 10.1016/s0006-2952(03)00288-0.
  36. Unver E, Tosun M, Olmez H, Kuzucu M, Cimen FK, Suleyman Z. (2019) The effect of taxifolin on cisplatin-induced pulmonary damage in rats: A biochemical and histopathological evaluation. Mediators of inflamm, 2019, 3740867. doi: 10.1155/2019/3740867.
  37. Vannini F, Kashfi K, Nath N. (2015) The dual role of iNOS in cancer. Redox biol, 6, 334-343. doi: 10.1016/j.redox.2015.08.009.
  38. Wagner MJ, Livingston JA, Patel SR, Benjamin RS. (2016) Chemotherapy for bone sarcoma in adults. J Oncol Pract, 12(3), 208-216. doi: 10.1200/JOP.2015.009944.
  39. Wang Z, Li YF, Han XY, Sun YS, Zhang LX, Liu W, Liu XX, Li W, Liu YY. (2018) Kidney protection effect of ginsenoside re and its underlying mechanisms on cisplatin-induced kidney injury. Cell Physiol Biochem, 48(5), 2219-2229. doi: 10.1159/000492562.
  40. Wu L, Gokden N, Mayeux PR. (2007) Evidence for the role of reactive nitrogen species in polymicrobial sepsis-induced renal peritubular capillary dysfunction and tubular injury. J Am Soc Nephrology, 18(6), 1807-1815. doi: 10.1681/ASN.2006121402.
  41. Wu W, Fu Y, Liu Z, Shu S, Wang Y, Tang C, Cai J, Dong Z. (2021) NAM protects against cisplatin-induced acute kidney injury by suppressing the PARP1/p53 pathway. Toxicol Appl pharmacol, 418, 115492. doi: 10.1016/j.taap.2021.115492.
  42. Yang R, Yang X, Zhang F. (2023) New Perspectives of Taxifolin in Neurodegenerative Diseases. Curr Neuropharmacol, 21(10), 2097. doi: 10.2174/1570159X21666230203101107.
  43. Yang X, He Z Zheng, Wang N, Mulinge M, Schmit JC, Steinmetz A, Seguin-Devaux C. (2021) Chemical constituents of Cassia abbreviata and their anti-HIV-1 activity. Molecules, 26(9), 2455. doi: 10.3390/molecules26092455.
  44. Zhang J, Zou Y, Cheng‐Jing Y, Xiang‐Heng, Wang, XP, Yu XJ, Li GS, Wang J. (2020) Pioglitazone alleviates cisplatin nephrotoxicity by suppressing mitochondria‐mediated apoptosis via SIRT1/p53 signalling. J Cell Mol Med, 24(20), 11718-11728. doi: 10.1111/jcmm.15782.
  45. Aldemir M, Okulu, Kösemehmetoğlu K, Ener, Topal F, Evirgen O, Gürleyik E, Avcı A. (2014) Evaluation of the protective effect of quercetin against cisplatin‐induced renal and testis tissue damage and sperm parameters in rats. Andrologia, 46(10), 1089-1097. doi: 10.1111/and.12197.
  46. Skinner R, Pearson, English M, Price L, Wyllie R, Coulthard M, Craft A. (1998) Cisplatin dose rate as a risk factor for nephrotoxicity in children. British J Cancer, 77(10), 1677-1682. doi: 10.1038/bjc.1998.276.
  47. Yang X, He Z Zheng, Wang N, Mulinge M, Schmit JC, Steinmetz A, Seguin-Devaux C. (2021) Chemical constituents of Cassia abbreviata and their anti-HIV-1 activity. Molecules, 26(9), 2455. doi: 10.3390/molecules26092455.
  48. Zhang J, Zou Y, Cheng‐Jing Y, Xiang‐Heng, Wang, XP, Yu XJ, Li GS, Wang J. (2020) Pioglitazone alleviates cisplatin nephrotoxicity by suppressing mitochondria‐mediated apoptosis via SIRT1/p53 signalling. J Cell Mol Med, 24(20), 11718-11728. doi: 10.1111/jcmm.15782.