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

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.