Exploring Esculetin's Protective Role: Countering Doxorubicin-Induced Oxidative Stress in Rat Heart

Year 2024, Volume: 4 Issue: 1, 44 - 52, 29.03.2024

Neslihan Öztürk , Medine Sibel Karağaç , Esra Nur Yeşilkent , Murat Isıyel , Hilal Tosun , Habibe Karadaş , Hamid Ceylan , Yeliz Demir

https://doi.org/10.5281/zenodo.10892230

Abstract

Doxorubicin (DOX) and other anthracyclines are potent chemotherapy drugs used against cancer; however, their clinical application is linked to significant and potentially life-threatening cardiotoxicity. Despite extensive research over many years, the available treatment choices are still constrained. DOX is typically believed to primarily affect mitochondria, and the characteristic feature of DOX-induced cardiotoxicity is mitochondrial dysfunction. In this study was designed to explore the protective effects of esculetin against DOX-induced cardiotoxicity in Sprague-Dawley rats, considering its known properties. Cardiotoxicity was induced by administering DOX via intraperitoneal injection at a weekly dosage of 5 mg/kg body weight for two consecutive weeks. Rats receiving DOX injections were simultaneously supplemented with esculetin at doses of 50 and 100 mg/kg body weight through intraperitoneal administration over the same period. The investigation, oxidative stress enzymes in heart tissue employed biochemical and molecular methods. Enzyme activities and expression levels of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were assessed in heart tissues.Intoxication with DOX resulted in a reduction in antioxidant status, affecting CAT and GPx and SOD. Both enzyme activity and mRNA expression decreased in the DOX group. There was an increase in DOX and esculetin combined groups. The present study proposes that DOX-induced detrimental effects on heart tissue are potentially mitigated by esculetin via modulation of oxidative stress.

Keywords

Cardiotoxicity, doxorubicin, esculetin, oxidative stress

Ethical Statement

Ethics committee approval was received for this study from the ethics committee of Atatürk University (Protocol Number: 2021/4–123).

Project Number

Ardahan Üniversitesi BAP birimi Proje No: 2021-003

Eskuletin'in Koruyucu Rolünü Keşfetmek: Sıçan Kalbinde Doksorubisinin Neden Olduğu Oksidatif Stresle Mücadele

Abstract

Doksorubisin (DOX) ve diğer antrasiklinler kansere karşı kullanılan güçlü kemoterapi ilaçlarıdır; ancak klinik uygulamaları önemli ve potansiyel olarak yaşamı tehdit eden kardiyotoksisite ile bağlantılıdır. Uzun yıllar süren kapsamlı araştırmalara rağmen, mevcut tedavi seçenekleri hala kısıtlıdır. DOX'un tipik olarak öncelikle mitokondriyi etkilediğine inanılır ve DOX kaynaklı kardiyotoksisitenin karakteristik özelliği mitokondriyal disfonksiyondur. Bu çalışma, bilinen özellikleri göz önünde bulundurularak Sprague-Dawley sıçanlarında DOX kaynaklı kardiyotoksisiteye karşı esculetin'in koruyucu etkilerini araştırmak üzere tasarlanmıştır. Kardiyotoksisite, DOX'un intraperitoneal enjeksiyon yoluyla haftalık 5 mg/kg vücut ağırlığı dozunda iki ardışık hafta boyunca uygulanmasıyla indüklenmiştir. DOX enjeksiyonu yapılan sıçanlara aynı süre boyunca 50 ve 100 mg/kg vücut ağırlığı dozlarında intraperitoneal uygulama yoluyla eş zamanlı olarak esculetin takviyesi yapılmıştır. Kalp dokusundaki oksidatif stres enzimlerinin araştırılmasında biyokimyasal ve moleküler yöntemler kullanılmıştır. Kalp dokularında katalaz (CAT), glutatyon peroksidaz (GPx) ve süperoksit dismutaz (SOD) enzim aktiviteleri ve ekspresyon seviyeleri değerlendirildi.DOX ile intoksikasyon, CAT ve GPx ve SOD'yi etkileyerek antioksidan durumda bir azalmaya neden oldu. DOX grubunda hem enzim aktivitesi hem de mRNA ekspresyonu azalmıştır. DOX ve esculetin kombine gruplarında ise artış görülmüştür. Bu çalışma, kalp dokusu üzerinde DOX'un neden olduğu zararlı etkilerin, oksidatif stresin modülasyonu yoluyla esculetin tarafından potansiyel olarak hafifletildiğini öne sürmektedir.

Keywords

Kardiyotoksisite, doksorubisin, esculetin, oksidatif stres

Ethical Statement

Ethics committee approval was received for this study from the ethics committee of Atatürk University (Protocol Number: 2021/4–123).

Project Number

Ardahan Üniversitesi BAP birimi Proje No: 2021-003

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