Engeletin’in NF-κB/iNOS ve Cyt-c/CASP-3 sinyal yolları aracılığıyla doksorubisin kaynaklı kardiyotoksisiteye karşı koruyucu etkileri

Yıl 2025, Cilt: 50 Sayı: 3, 872 - 882, 30.09.2025

İrfan Çınar , Serdar Akyel , Büşra Dincer

https://doi.org/10.17826/cumj.1717960

Öz

Amaç: Bu çalışmanın amacı, Engeletin’in (ENG) Sitokrom c/ kaspaz 3 (Cyt-c/CASP-3) yoluyla apopitoz, Transforme Edici Büyüme Faktörü Beta 1 (TGF-β1) yoluyla fibrozis ve Doksorubisin (DOX) kaynaklı kardiyotoksisitede Nükleer Faktör Kappa B/ İndüklenebilir Nitrik Oksit Sentaz (NF-κB/iNOS) sinyalleme kaskadı yoluyla oksidatif durum üzerindeki etkilerini değerlendirmektir.
Gereç ve Yöntem: Çalışma beş gruptan oluşmaktadır: Kontrol, DOX (1 µM), DOX + ENG 10 µM, DOX + ENG 20 µM ve DOX + ENG 40 µM. Proinflamatuvar, apopitotik ve fibrotik sinyal kaskadlarındaki gen ekspresyon seviyeleri gerçek zamanlı ters transkripsiyon-kantitatif polimeraz zincir reaksiyonu analiz ile kantifiye edildi. Oksidatif stres parametreleri spektrofotometrik analiz ile belirlendi.
Bulgular: Bulgular ENG'nin kardiyomiyosit (H9c2) hücre canlılığını önemli ölçüde iyileştirdiğini, laktat dehidrogenaz (LDH) seviyelerini azalttığını (%52) ve DOX kaynaklı reaktif oksijen türleri (ROS) oluşumunu zayıflattığını göstermektedir. Dahası, ENG NF-κB (DOX: 2.220.09; DOXENG 10: 2.00 0.02; DOXENG 20: 1.800.06; DOXENG 40:1.230.05), inaktivasyonu yoluyla proinflamatuvar sitokinleri ve inflamatuvar enzimleri aşağı düzenledi. Veriler ayrıca ENG’nin apopitotik yolda Cyt-c, CASP-3, ve B-hücre Lenfoma 2/ Bcl-2 İlişkili X Proteini (Bcl2/BAX) (ekspresyonunu aşağı düzenleyerek kardiyomiyosit apopitozunu engellediğini gösterdi.
Sonuç: Genel olarak, bu gözlemler ENG’nin oksidatif stresi, kardiyomiyofibrozu ve apopitozu zayıflatarak DOX kaynaklı kardiyotoksisite üzerinde kardiyoprotektif etkisi olduğunu göstermektedir.

Anahtar Kelimeler

Engeletin , doksorubisin , kardiyotoksisite , apoptozis

Proje Numarası

KÜBAP-01/2022-26

Protective effects of engeletin on doxorubicin-induced cardiotoxicity via NF-κB/iNOS and Cyt-c/CASP-3 signaling pathways

Öz

Purpose: The goal of this study was to assess the effects of Engeletin (ENG) on apoptosis via the Cytochrome c/ Caspase 3 (Cyt-c/CASP-3) pathway, fibrosis via the Transforming Growth Factor Beta 1 (TGF-β1) pathway, and oxidative status via the Nuclear Factor kappa-light-chain-enhancer of activated B cells/ Inducible Nitric Oxide Synthase (NF-κB/iNOS) signaling cascade, in doxorubicin (DOX)-induced cardiotoxicity.
Materials and Methods: The study sample included five groups: Control, DOX (1 µM), DOX + ENG 10 µM, DOX + ENG 20 µM, and DOX + ENG 40 µM. Gene expression levels in the proinflammatory, apoptotic, and fibrotic signal cascades were quantified by real-time reverse transcription-quantitative polymerase chain reaction analysis. Oxidative stress parameters were determined by spectrophotometric analysis.
Results: Data demonstrate that ENG substantially improved H9c2 cell viability, diminished lactate dehydrogenase (LDH) levels (52%), and attenuated DOX-induced ROS generation. Furthermore, ENG down-regulated proinflammatory cytokines and inflammatory enzymes through NF-κB inactivation. The data also showed that ENG inhibited cardiomyocyte apoptosis by downregulating Cyt-c, CASP-3, and B-cell lymphoma 2/ Bcl-2-associated X protein (Bcl2/BAX) expression in the apoptotic pathway.
Conclusion: These observations suggest the cardioprotective effect of ENG on DOX-induced cardiotoxicity by attenuating oxidative stress, cardiomyofibrosis, and apoptosis.

Anahtar Kelimeler

Engeletin , doxorubicin , cardiotoxicity , apoptosis

Proje Numarası

KÜBAP-01/2022-26

Kaynakça

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