Restorative Potential of Bromelain Against Doxorubicin Hepatotoxicity

Öz

Background: Doxorubicin (DOX) is a commonly used drug in cancer treatment but has acute and chronic toxic side effects.  Bromelain (BRM),which is a protease enzyme, has antioxidant activities. In the current study it was aimed to investigate the potential effects of BRM on DOX induced liver injury. 

Materials and Methods: Four equal groups (n:7) of Wistar albino male rats were used: control, DOX, BRM, DOX+BRM. Liver tissues of all groups were evaluated for histopathology, inflammation,  apoptosis, regenerative, and vascular mechanical changes.
Results: In the DOX group, histological damage was evident (p<0.005), also tumor necrosis factor (TNF-α), interleukin 6 (IL-6), caspase-3, and proliferating cell nuclear antigen (PCNA) immunoreactivities were increased (p<0.005), whereas no statistically significant changes was observed for vascular endothelial growth factor (VEGF) expression (p>0.05). In the DOX + BRM group, BRM reduced overexpression of inflammatory cytokines, caspase-3 and PCNA (p<0.005). Additionally, VEGF expression was found to be statistically higher (p<0.005) in the DOX+BRM group when compared to the DOX group. Conclusions: BRM exhibited hepatoprotective potential against DOX hepatotoxicity in rats.

Conclusions: BRM exhibited hepatoprotective potential against DOX hepatotoxicity in rats.

Anahtar Kelimeler

• Doxorubicin
• Bromelain
• Hepatotoxicity
• Inflammation
• Caspase-3/PCNA/VEGF

Etik Beyan

Ethical approval for this study was obtained from the Harran University Local Ethics Committee for Animal Experiments (approval no. 2004-006/01-16; date: November 11, 2024).

Teşekkür

The author would like to thank Prof. Fatih Uckardes (Department of Biostatistics and Medical Informatics, Faculty of Medicine, Adiyaman University, Türkiye) for his assistance with the statistical analysis.

Bromelain'in Doksorubisin Kaynaklı Karaciğer Toksisitesine Karşı İyileştirici Potansiyeli

Öz

Amaç: Doksorubisin (DOX), kanser tedavisinde yaygın olarak kullanılan bir ilaçtır ancak, akut ve kronik toksik yan etkileri vardır. Bromelain (BRM), bir proteaz enzimi olup antioksidan aktiviteye sahiptir. Mevcut çalışmada BRM'nin DOX kaynaklı karaciğer hasarı üzerindeki potansiyel etkilerinin araştırılması amaçlandı. 
Materyal ve metod: Wistar albino erkek sıçanlardan oluşan dört eşit grup (n:7) kullanıldı: kontrol, DOX, BRM, DOX+BRM. Tüm grupların karaciğer dokuları histopatoloji, inflamasyon, apoptoz, rejenerasyon ve vasküler mekanik değişiklikler açısından değerlendirildi. 
Bulgular: DOX grubunda histolojik hasar belirgindi (p<0,005), ayrıca tümör nekroz faktörü (TNF-α), interlökin 6 (IL-6), kaspaz-3 ve prolifere hücre nükleer antijeni (PCNA) immünreaktiviteleri artarken (p<0,005), vasküler endotelyal büyüme faktörünün (VEGF)  ekspresyonunda istatistiksel olarak anlamlı bir değişiklik gözlenmedi (p>0,05).  DOX + BRM grubunda, BRM, inflamatuar sitokinler, kaspaz-3 ve PCNA'nın aşırı ekspresyonunu azalttı (p<0,005). Ayrıca, DOX+BRM grubunda VEGF ekspresyonunun, DOX grubuna kıyasla istatistiksel olarak arttığı (p<0,005) gözlemlendi. 
Sonuç: BRM, sıçanlarda DOX'un neden olduğu hepatotoksisiteye karşı hepatoprotektif etki gösterdi. 

Anahtar Kelimeler

• Doksorubisin
• Bromelain
• Hepatotoksisite
• İnflamasyon
• Kaspaz-3/PCNA/VEGF

Destekleyen Kurum

No financial support was received for this study.

Etik Beyan

Ethical approval for this study was obtained from the Harran University Local Ethics Committee for Animal Experiments (approval no. 2004-006/01-16; date: November 11, 2024).

Teşekkür

Yazar, istatistiksel analiz konusunda sağladığı destekten dolayı Prof. Dr. Fatih Uckardes’e (Adıyaman Üniversitesi Tıp Fakültesi Biyoistatistik ve Tıp Bilişimi Anabilim Dalı, Türkiye) teşekkür eder.

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