Nerolidol attenuates oxidative stress, inflammation, and apoptosis by modulating nrf2/mapk signaling pathways in doxorubicin-induced acute cardiotoxicity in rats

Seenipandi Arunachalam, M. F. Nagoor Meeran, Sheikh Azimullah, Charu Sharma, Sameer N. Goyal, Shreesh Ojha

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

The clinical usage of doxorubicin (DOX), a potent anthracycline antineoplastic drug, is often limited by its cardiotoxic effects. Thus, for improving usage of DOX, the aim of this study was to assess the cardioprotective effects of nerolidol (NERO) in a rat model of DOX-induced acute cardiotoxicity and examine underlying molecular mechanisms that contribute to these effects. To induce acute cardiotoxicity male albino Wistar rats were injected with single dose intraperitoneal DOX (12.5 mg/kg). The rats were treated with NERO (50 mg/kg, orally) for five days. DOX-injected rats showed elevated levels of cardiac marker enzymes and enhanced oxidative stress markers along with altered Nrf2/Keap1/HO-1 signaling pathways. DOX administration also induced the activation of NF-κB/MAPK signaling and increased the levels and expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) as well as expression of inflammatory mediators (iNOS and COX-2) in the heart. DOX also triggered DNA damage and apoptotic cell death in the myocardium. Additionally, histological studies revealed structural alterations of the myocardium. NERO treatment exhibited protection against the deleterious results of DOX on myocardium, as evidenced by the restoration of altered biochemical parameters, mitigated oxidative stress, inflammation, and apoptosis. The findings of the present study demonstrate that NERO provides cardioprotective effects against DOX-induced acute cardiotoxicity attributed to its potent antioxidant, anti-inflammatory, and antiapoptotic activities through modulating cellular signaling pathways.

Original languageEnglish
Article number984
JournalAntioxidants
Volume10
Issue number6
DOIs
Publication statusPublished - Jun 2021

Keywords

  • Acute cardiotoxicity
  • Cardioprotective
  • Doxorubicin
  • Inflammation
  • Nerolidol
  • Oxidative stress
  • Sesquiterpene

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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