Nootkatone Ameliorates Doxorubicin Induced Myocardial Injury through Modulation of NF-κB Signals and Oxidative Stress

Suhail Al-Salam, Karthishwaran Kandhan, Manjusha Sudhadevi, Saeed Tariq

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Background/Aims: Doxorubicin (DOXO) is a potent chemotherapeutic drug that is used in the treatment of a large number of cancers. Despite its important chemotherapeutic characteristics, its usage is limited because of the serious side effects; the most noticeable is cardiotoxicity which can manifest acutely or years after completion of treatment leading to left ventricular dysfunction, dilated cardiomyopathy and heart failure. Nootkatone (NK) is a recognized bioactive compound isolated from the heartwood of Cupressus nootkatensis and has been reported to have antiseptic, antioxidant, and anti-allergic activities. Methods: Male C57B6/J mice were used for mice model of DOXO-cardiac toxicity. Mice were given either DOXO or NK or DOXO+NK or vehicle (normal saline) after which the mice again had free access to food and water. Heart and plasma samples were collected 5 days after DOXO administration and were used for immunohistochemistry, electron microscopy and enzyme linked immunosorbent assay (ELISA). Results: There were significant reduction in inflammatory markers in hearts of DOXO-NK-treated mice when compared with DOXO-treated mice. Moreover, there were significant increase in antioxidant proteins and reduction of oxidative stress in hearts of DOXO-NK-treated mice when compared with DOXO-treated mice. There was a significant reduction in myocardial damage as shown by significant reduction of troponin I in DOXO-NK-treated mice when compared with DOXO-treated mice. Conclusion: Nootkatone improves DOXO-induced myocardial injury through modulation of NF-κB signals and reduction of oxidative stress.

Original languageEnglish
Pages (from-to)401-417
Number of pages17
JournalCellular Physiology and Biochemistry
Volume56
Issue number4
DOIs
Publication statusPublished - 2022

Keywords

  • Doxorubicin
  • Heart
  • Myocardial injury
  • Oxidative stress

ASJC Scopus subject areas

  • Physiology

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