PMID- 34170670
OWN - NLM
STAT- MEDLINE
DCOM- 20210708
LR  - 20210708
IS  - 1520-5118 (Electronic)
IS  - 0021-8561 (Linking)
VI  - 69
IP  - 26
DP  - 2021 Jul 7
TI  - Nerolidol, a Sesquiterpene from the Essential Oils of Aromatic Plants, Attenuates 
      Doxorubicin-Induced Chronic Cardiotoxicity in Rats.
PG  - 7334-7343
LID - 10.1021/acs.jafc.0c05667 [doi]
AB  - The clinical usage of doxorubicin (DOX), a potent anthracycline antineoplastic 
      drug, is limited due to its cardiotoxicity. The aim of this study was to assess 
      the possible cardioprotective effects of nerolidol (NERO) in a rat model of 
      DOX-induced chronic cardiotoxicity and the underlying molecular mechanisms. DOX 
      (2.5 mg/kg) was injected intraperitoneally once in a week for 5 weeks to induce 
      chronic cardiotoxicity in male albino Wistar rats. The rats were treated with 
      NERO (50 mg/kg, orally) 6 days a week for a duration of 5 weeks. DOX-injected 
      rats showed a significant decline in cardiac function, elevated levels of serum 
      cardiac marker enzymes, and enhanced oxidative stress markers along with altered 
      PI3K/Akt and Nrf2/Keap1/HO-1 signaling pathways. DOX also triggered the 
      activation of NF-kappaB/MAPK signaling and increased the levels/expression of 
      proinflammatory cytokines (TNF-alpha, IL-6, and IL-1beta) and expression of inflammatory 
      mediators (iNOS and COX-2) in the heart. DOX activated NLRP3 
      inflammasome-mediated pyroptotic cell death along with fibrosis, mitochondrial 
      dysfunction, DNA damage, and apoptosis in the myocardium. Additionally, 
      histological studies, TUNEL staining, and myocardial lesions revealed structural 
      alterations of the myocardium. NERO treatment showed considerable protective 
      effects on the biochemical and molecular parameters studied. The findings 
      demonstrate that NERO protects against DOX-induced chronic cardiotoxicity and the 
      observed cardioprotective effects are attributed to its potent antioxidant and 
      free radical scavenging properties.
FAU - Meeran, M F Nagoor
AU  - Meeran MFN
AD  - Department of Pharmacology and Therapeutics, College of Medicine and Health 
      Sciences, United Arab Emirates University, PO Box-17666, Al Ain 17666, United 
      Arab Emirates.
FAU - Azimullah, Sheikh
AU  - Azimullah S
AD  - Department of Pharmacology and Therapeutics, College of Medicine and Health 
      Sciences, United Arab Emirates University, PO Box-17666, Al Ain 17666, United 
      Arab Emirates.
FAU - Mamoudh, Hebaallah Hashiesh
AU  - Mamoudh HH
AD  - Department of Pharmacology and Therapeutics, College of Medicine and Health 
      Sciences, United Arab Emirates University, PO Box-17666, 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, PO Box-17666, Al Ain 17666, United Arab Emirates.
FAU - Kumar, Sanjay
AU  - Kumar S
AD  - Division of Hematology, Department of Nephrology, Mayo Clinic, Rochester, 
      Minnesota 55905, United States.
AD  - Department of Life Science, School of Basic Science and Research, Sharda 
      University, Greater Noida, Uttar Pradesh, India 201310.
FAU - Goyal, Sameer N
AU  - Goyal SN
AD  - Shri Vile Parle Kelavani Mandal's, Institute of Pharmacy, Dhule, Maharashtra 424 
      001, 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, PO Box-17666, Al Ain 17666, United 
      Arab Emirates.
LA  - eng
PT  - Journal Article
DEP - 20210625
PL  - United States
TA  - J Agric Food Chem
JT  - Journal of agricultural and food chemistry
JID - 0374755
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Oils, Volatile)
RN  - 0 (Sesquiterpenes)
RN  - 80168379AG (Doxorubicin)
RN  - QR6IP857S6 (nerolidol)
SB  - IM
MH  - Animals
MH  - Antibiotics, Antineoplastic/metabolism/toxicity
MH  - Apoptosis
MH  - Cardiotoxicity/drug therapy/metabolism
MH  - Doxorubicin/toxicity
MH  - Kelch-Like ECH-Associated Protein 1/metabolism
MH  - Male
MH  - Myocardium/metabolism
MH  - NF-E2-Related Factor 2/genetics/metabolism
MH  - *Oils, Volatile/pharmacology
MH  - Oxidative Stress
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - *Sesquiterpenes/metabolism
OTO - NOTNLM
OT  - apoptosis
OT  - doxorubicin
OT  - myocardial fibrosis
OT  - nerolidol
OT  - sesquiterpene
EDAT- 2021/06/26 06:00
MHDA- 2021/07/09 06:00
CRDT- 2021/06/25 17:09
PHST- 2021/06/26 06:00 [pubmed]
PHST- 2021/07/09 06:00 [medline]
PHST- 2021/06/25 17:09 [entrez]
AID - 10.1021/acs.jafc.0c05667 [doi]
PST - ppublish
SO  - J Agric Food Chem. 2021 Jul 7;69(26):7334-7343. doi: 10.1021/acs.jafc.0c05667. 
      Epub 2021 Jun 25.