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

Year 2024, Volume: 35 Issue: 1, 1 - 7, 04.07.2024

Gökhan Akçakavak , Özhan Karataş , Zeynep Çelik , Ayşenur Tural , Osman Dağar , Ahmed Abduljabbar , Bahadır Kılınç , Mehmet Tuzcu

https://doi.org/10.35864/evmd.1458328

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.

Keywords

Cisplatin, histopathology, iNOS, taxifolin, p53.

Ethical Statement

Selcuk University Faculty of Veterinary Medicine Experimental Animal Production and Research Center Ethics Committee approved the ethical compliance of the study (Approval No: 2024/056)

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

Abstract

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.

Keywords

histopatoloji, iNOS, taksifolin, p53, sisplatin

Ethical Statement

.

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