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KMID : 1200820210210040805
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Oriental Pharmacy and Experimental Medicine
2021 Volume.21 No. 4 p.805 ~ p.814
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Ameliorative effect of Dillenia indica fruits against doxorubicin-induced cardiomyocyte toxicity
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Tene Kalyani
Kumar Kalyan
Pemmaraju Deepak Bharadwaj
Kumar Jagadeesh
Shantanu P. A.
Gogoi Ranadeep
Naidu V. G. M.
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Abstract
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Drug-induced cardiotoxicity is a significant concern in cancer patients, and therefore cardio-oncology is gaining more attention. Doxorubicin (Dox) is a potent anticancer drug used against various malignancies, with cardiotoxicity as a dose-limiting factor. Although the mechanism of Dox-mediated cardiotoxicity is not fully understood, it is thought to encompass oxidative stress during the therapy leading to cardiotoxicity in cancer patients. Several oxidative stress-induced diseases and drug-induced toxicities can be effectively ameliorated using bioactive plant constituents. Dillenia indica (DI) is one such plant belonging to the family Dilleniaceae and is used as an ethno-medicinal agent for the treatment of various oxidative stress-mediated diseases like diabetes and cancer. In this study, we have evaluated the protective effect of the hydroalcoholic extract of Dillenia indica fruits (HADI) against the Dox-induced cardiomyocyte toxicity. The HADI was further evaluated for its efficacy in a Dox-induced cardiotoxicity models. Antioxidant assays (ABTS and DPPH) revealed a strong antioxidant potential of HADI. In vitro assay results indicated that pre-treatment with HADI had shown protective activity and reduced the ROS generation in H9c2 cell line. Non-invasive methods like high-frequency ultrasonography and electrocardiography were applied to evaluate the real time cardiac parameters. It was also found that pre-treatment with HADI restored functional parameters like ejection fraction, stroke volume as well as elevation of the T wave induced by Dox. Whereas the Dox treated mice had elevated levels of cardiac functional enzymes like creatinine kinase (CK-MB) and lactate dehydrogenase indicating the severity of cardiomyocyte toxicity. The results indicated that HADI pre-treatment has significantly reduced the upregulated enzyme levels. Taken together, our findings indicated that HADI ameliorated the Dox-induced cardiomyocyte toxicity by modulating the upregulated reactive oxygen species.
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KEYWORD
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Cardio-oncology, Doxorubicin, Cardiomyocytes, Reactive oxygen species (ROS)
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