Restorative Potential of Bromelain Against Doxorubicin Hepatotoxicity

Abstract

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.

Keywords

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

Ethical Statement

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).

Thanks

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

Abstract

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. 

Keywords

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

Supporting Institution

No financial support was received for this study.

Ethical Statement

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).

Thanks

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.

References

1. Topuz Ş, Taşgıt A, Cilesiz E, Gökce R, Ülger DA, Oğuz ŞS. Views of mothers about national newborn screening tests performed in Turkey. Health. 2021;73:81-1.
2. Erdal İ, Kahraman AB, Yıldız Y, Yalçın SS. Newborn screening programs promote vaccine acceptance among parents in Turkey: A cross-sectional study. Postgrad Med. 2025;137(5):423-38.
3. Wright SJ, Ulph F, Dharni N, Payne K. Eliciting preferences for information provision in newborn bloodspot screening programs. Value Health. 2017;20(4):651-61.
4. Newborn Screening Program [homepage on the Internet]. Ankara: Turkish Ministry of Health, General Directorate of Public Health [cited 03 Mar 2026]. Available from: https://hsgm.saglik.gov.tr/tr/tarama-programlari/ntp.html
5. Newborn Screening Program Brochure [homepage on the Internet]. Ankara: Turkish Ministry of Health, General Directorate of Public Health [cited 03 Mar 2026]. Available from: https://hsgm.saglik.gov.tr/depo/birimler/cocuk-ergen-sagligi-db/Dokumanlar/Afisler-Brosurler/Yenidogan_Tarama_Programi_Brosur.pdf
6. İçke S, Genç RE. National newborn screening tests carried out with heel lance and their importance. J Pediatr Res. 2017.
7. Evcili F, Cesur B, Yurtsal B, Kaya N. Views of mothers about newborn screening tests and participation status in screening programs. Mersin Univ J Health Sci. 2017;10:25-35.
8. Turkish Statistical Institute (TÜİK). Statistics on Family, 2024 [homepage on the Internet]. [cited 14 May 2025]. Available from: https://veriportali.tuik.gov.tr/tr/press/53898

9. Okyay P, Abacıgil F. Reliability and validity study of health literacy scales in Turkey. Turkey Health Literacy Scale-32 (TSOY-32). Ankara: Turkish Ministry of Health, 2016:1025.
10. Botkin JR, Rothwell E, Anderson RA, et al. Public attitudes regarding the use of residual newborn screening specimens for research. Pediatrics. 2012;129(2):231-8.
11. Nicholls SG, Southern KW. Parental decision-making and acceptance of newborn bloodspot screening: an exploratory study. PLoS One. 2013;8(11):e79441.
12. Gonçalves-Fernández ML, Pino-Juste M. Health literacy in healthy adults: A systematic review of recent evidence. Aten Primaria. 2025;57(11):103300.
13. Sentell T, Kostareva U, Taira DA, Tolentino NK, Polovina Y, Kreif T, et al. Health literacy and the Pacific: A scoping literature review of journal articles. Public Health. 2026;250:106051.
14. Aygun O, Topcu M. The relationship between parental health literacy levels and anthropometric measurements of children in Turkey. BMC Pediatr. 2023;23(1):559.
15. Alp S, Kara NO. A Research to Examine Parental Health Literacy and Use of Pediatric Services. Selçuk University Journal of Social Sciences Institute. 2023;50:1-19.