PMID- 34205494
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210710
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 10
IP  - 6
DP  - 2021 Jun 21
TI  - Nerolidol Attenuates Oxidative Stress, Inflammation, and Apoptosis by Modulating 
      Nrf2/MAPK Signaling Pathways in Doxorubicin-Induced Acute Cardiotoxicity in Rats.
LID - 10.3390/antiox10060984 [doi]
LID - 984
AB  - 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-kappaB/MAPK 
      signaling and increased the levels and expression of pro-inflammatory cytokines 
      (TNF-alpha, IL-6, and IL-1beta) 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.
FAU - Arunachalam, Seenipandi
AU  - Arunachalam S
AD  - Department of Pharmacology and Therapeutics, College of Medicine and Health 
      Sciences, United Arab Emirates University, Al Ain 17666, United Arab Emirates.
FAU - Nagoor Meeran, M F
AU  - Nagoor Meeran MF
AUID- ORCID: 0000-0001-6863-7372
AD  - Department of Pharmacology and Therapeutics, College of Medicine and Health 
      Sciences, United Arab Emirates University, Al Ain 17666, United Arab Emirates.
FAU - Azimullah, Sheikh
AU  - Azimullah S
AUID- ORCID: 0000-0002-0788-7164
AD  - Department of Pharmacology and Therapeutics, College of Medicine and Health 
      Sciences, United Arab Emirates University, Al Ain 17666, United Arab Emirates.
FAU - Sharma, Charu
AU  - Sharma C
AD  - Department of Internal Medicine, College of Medicine and Health Sciences, United 
      Arab Emirates University, Al Ain 17666, United Arab Emirates.
FAU - Goyal, Sameer N
AU  - Goyal SN
AD  - Shri Vile Parle Kelavani Mandal's Institute of Pharmacy, Dhule 424001, India.
FAU - Ojha, Shreesh
AU  - Ojha S
AUID- ORCID: 0000-0001-7801-2966
AD  - Department of Pharmacology and Therapeutics, College of Medicine and Health 
      Sciences, United Arab Emirates University, Al Ain 17666, United Arab Emirates.
LA  - eng
GR  - CMHS/CMHS, UAEU/
PT  - Journal Article
DEP - 20210621
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC8235529
OTO - NOTNLM
OT  - acute cardiotoxicity
OT  - cardioprotective
OT  - doxorubicin
OT  - inflammation
OT  - nerolidol
OT  - oxidative stress
OT  - sesquiterpene
COIS- The authors have no competing interests to declare. The funders of the research 
      grant have no role in study design, interpretation, and publication. The received 
      funding did not lead to any conflict of interests regarding the publication of 
      this manuscript.
EDAT- 2021/07/03 06:00
MHDA- 2021/07/03 06:01
PMCR- 2021/06/21
CRDT- 2021/07/02 01:24
PHST- 2021/04/08 00:00 [received]
PHST- 2021/05/06 00:00 [revised]
PHST- 2021/05/13 00:00 [accepted]
PHST- 2021/07/02 01:24 [entrez]
PHST- 2021/07/03 06:00 [pubmed]
PHST- 2021/07/03 06:01 [medline]
PHST- 2021/06/21 00:00 [pmc-release]
AID - antiox10060984 [pii]
AID - antioxidants-10-00984 [pii]
AID - 10.3390/antiox10060984 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2021 Jun 21;10(6):984. doi: 10.3390/antiox10060984.