Sisplatin uygulanan sıçanlarda selenyum takviyesinin böbrek fonksiyonu üzerindeki koruyucu etkisinin araştırılması

Year 2024, Volume: 49 Issue: 2, 304 - 313, 30.06.2024

Melek Altunkaya , Gülsüm Abuşoğlu , Bahadir Ozturk

https://doi.org/10.17826/cumj.1400660

Abstract

Amaç: Selenyum, hücreleri cisplatin kaynaklı toksisitenin önemli bir belirteci olan oksidatif stresten koruma yeteneğine sahip önemli bir antioksidan ve antikarsinojendir. Bu çalışma, böbrek hasarı ile ilişkili kreatinin, nötrofil jelatinaz ile ilişkili lipokalin (NGAL) ve galektin-3'teki değişiklikleri inceleyerek, cisplatin kaynaklı nefrotoksisitede selenyumun serbest radikaller üzerindeki etkisini ortaya çıkarmayı amaçlamıştır.
Gereç ve Yöntem: 60 günlük 24 Wistar albino sıçan eşit olarak dört gruba ayrıldı: kontrol, cisplatin, selenyum ve cisplatin+selenyum. Deney, sıçanların doğumundan sonraki 39. günde başladı. Kontrollere intraperitoneal olarak tek doz fizyolojik salin uygulandı. Selenyum ve cisplatin+selenyum gruplarındaki sıçanlara 21 gün boyunca günde 1 mg/kg selenyum gastrik gavaj yoluyla verildi. Cisplatin ve cisplatin+selenyum gruplarındaki sıçanlara 57. günde 7,5 mg/kg cisplatin intraperitoneal olarak uygulandı. Deney, cisplatin uygulamasından üç gün sonra sonlandırıldı. Doku örnekleri selenyum için ICP-MS yöntemi, plazma kreatinin için biyokimyasal yöntem, NGAL ve galektin-3 için ELISA yöntemi kullanılarak analiz edildi.
Bulgular: Böbrek dokusu selenyum düzeyleri selenyum takviyesi verilen gruplarda anlamlı derecede yüksekti (kontrol;146.8 ± 10.8 ng/dl, selenyum;520.2 ± 31.2 ng/dl, cisplatin;140 ± 6.4 ng/dl, cisplatin + selenyum; 363.4 ± 33.6 ng/dl (). Plazma kreatinin seviyeleri cisplatin uygulanan gruplarda istatistiksel olarak anlamlı derecede yüksekti (kontrol; 0.33 ± 0.01 mg/dl, selenyum; 0.30 ± 0.01 mg/dl, cisplatin; 0.47 ± 0.02 mg/dl, cisplatin + selenyum; 0.45 ± 0.04). Böbrek dokusunda gruplar arasında NGAL düzeyinde fark bulunmazken, Galectin-3 düzeyinde diğer gruplara göre cisplatin grubunda artış görüldü. Bu artış cisplatin+selenyum grubunda cisplatin grubuna göre daha düşüktü. Kalp dokusu NGAL ve galektin-3 düzeyleri cisplatin grubunda daha yüksekti.
Sonuç: Selenyum takviyesinin, kreatinin, NGAL ve galektin-3 seviyelerindeki değişikliklerden de anlaşılacağı üzere cisplatinin neden olduğu nefrotoksisite ve kardiyotoksisite üzerinde iyileştirici bir etkisi olabilir.

Keywords

Böbrek, kalp, cisplatin, selenyum, NGAL, galektin-3

Ethical Statement

This study was approved by the Animal Experiments Ethics Committee of Selçuk University Experimental Medicine Application and Research Center with decision number 2023-23, dated April 28, 2023.

Supporting Institution

This work was financially supported by the Scientific Research Projects (BAP) Department of Selçuk University (23401079).

Project Number

23401079

Investigation of the protective effect of selenium supplementation on renal function in cisplatin-administered rats

Abstract

Purpose: Selenium is an important antioxidant and anticarcinogen with the ability to protect cells from oxidative stress, a significant marker of cisplatin-induced toxicity. This study aimed to reveal the effect of selenium on free radicals in cisplatin-induced nephrotoxicity by examining changes in creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and galectin-3, which are associated with kidney damage.
Materials and Methods: Twenty-four Wistar albino rats, aged 60 days, were equally divided into four groups: control, cisplatin, selenium, and cisplatin+selenium. The experiment started on the 39th day after the rats were born. Controls were intraperitoneally administered a single dose of physiological saline. Rats in the selenium and cisplatin+selenium groups were administered 1 mg/kg of selenium by gastric gavage per day for 21 days. The rats in the cisplatin and cisplatin+selenium groups were intraperitoneally administered 7.5 mg/kg of cisplatin on the 57th day. The experiment was terminated 3 days after single-dose administration. Tissue samples were analyzed using the ICP-MS method for selenium, the biochemical method for plasma creatinine, and the ELISA method for NGAL and galectin-3.
Results: Kidney tissue selenium levels were significantly higher in the selenium-supplemented groups (control;146.8 ± 10.8 ng/dl, selenium;520.2 ± 31.2 ng/dl, cisplatin;140 ± 6.4 ng/dl; cisplatin + selenium; 363.4 ± 33.6 ng/dl). Plasma creatinine levels were statistically significantly higher in the cisplatin-administered groups (control; 0.32 ± 0.01 mg/dl, selenium; 0.32 ± 0.01 mg/dl, cisplatin; 0.47 ± 0.02 mg/dl; cisplatin + selenium; 0.45 ± 0.04). There was no difference in kidney tissue NGAL levels; however, galectin-3 levels were significantly increased in the cisplatin group compared with the other groups. This increase was lower in the cisplatin+selenium group than in the cisplatin group. Heart tissue NGAL and galectin-3 levels were higher in the cisplatin group.
Conclusion: Selenium supplementation may have a healing effect on the nephrotoxicity and cardiotoxicity caused by cisplatin, as indicated by changes in creatinine, NGAL, and galectin-3 levels.

Keywords

kidney, heart, cisplatin, selenium, NGAL, galectin-3

Project Number

23401079

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