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Ameliorative effect of Dillenia indica fruits against doxorubicin-induced cardiomyocyte toxicity

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Abstract

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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Abbreviations

DPPH:

2,2-Diphenyl-1-picrylhydrazyl

ABTS:

(2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid))

DCFDA:

2′,7′-Dichlorofluorescin diacetate

DNTB:

(5,5′-Dithio-bis-[2-nitrobenzoic acid])

CK-MB:

Creatine kinase-MB

LDH:

Lactate dehydrogenase

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Acknowledgements

The authors would like to acknowledge the Department of Pharmaceuticals (DOP), India. We would also like to acknowledge the National Mission On Himalayan Studies (NMHS), G.B Plant National Institute of Himalayan Environment and Sustainable Development (GBPNIHESD), India. Ref No: GBPI/NMHS-2017-18/HSF-02.

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Authors and Affiliations

  1. Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Guwahati, India

    Kalyani Tene & Ranadeep Gogoi

  2. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Guwahati, Assam, 781102, India

    Kalyan Kumar, Deepak Bharadwaj Pemmaraju, Jagadeesh Kumar, P. A. Shantanu & V. G. M. Naidu

  3. Biological Sciences and Technology Division, CSIR-North-East Institute of Science and Technology, Jorhat, Assam, 785006, India

    Ranadeep Gogoi

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  1. Kalyani Tene
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Correspondence to Ranadeep Gogoi or V. G. M. Naidu.

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Ethical statement

The study was approved by the Institutional Animal Ethics Committee (IAEC), Guwahati, India (NIPS/NIPER/18/02).

Conflict of interest

Kalyani Tene has no conflict of interest. Kalyan Kumar has no conflict of interest. Deepak Bharadwaj Pemmaraju has no conflict of interest. Jagadeesh Kumar has no conflict of interest. P. A. Shantanu has no conflict of interest. Ranadeep Gogoi has no conflict of interest. V. G. M. Naidu has no conflict of interest.

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Tene, K., Kumar, K., Pemmaraju, D.B. et al. Ameliorative effect of Dillenia indica fruits against doxorubicin-induced cardiomyocyte toxicity. ADV TRADIT MED (ADTM) 21, 805–814 (2021). https://doi.org/10.1007/s13596-020-00510-1

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