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http://crossmark.crossref.org/dialog/?doi=10.1007/s00280-016-3233-1&domain=pdf
Web End = Cancer Chemother Pharmacol (2017) 79:399409
DOI 10.1007/s00280-016-3233-1
ORIGINAL ARTICLE
http://crossmark.crossref.org/dialog/?doi=10.1007/s00280-016-3233-1&domain=pdf
Web End = Modulation ofcyclophosphamide-induced cardiotoxicity bymethyl palmitate
DinaS.El-Agamy1,2 MohamedA.Elkablawy3,4 HanyM.Abo-Haded5
Abstract
Purpose Cyclophosphamide (CP) is a frequently used anticancer and immunosuppressant although its use has been associated with severe cardiotoxicity. The present study examined the ability of methyl palmitate (MP) to counteract CP-induced cardiotoxicity.
Methods Adult male Wistar rats were divided into four groups. The rst one served as control while the second received a single injection of CP (200 mg/kg, i.p.). The other two groups were administered MP at two dierent dose levels (300, 400mg/kg) for 10 days before and 7 days after CP single injection.
Results CP injection resulted in marked cardiac injury as presented by ECG abnormal changes, elevation of serum creatine kinase-MB (CK-MB), cardiac troponin I, troponin T and lactate dehydrogenase (LDH) and enormous histopathological lesions. Moreover, CP-induced oxidative stress as it elevated malondialdehyde (MDA) and
* Dina S. [email protected]; [email protected]
1 Present Address: Department ofPharmacology andToxicology, College ofPharmacy, Taibah University, P.O. Box344, Al-MadinahAl-Munawwarah30001, SaudiArabia
2 Department ofPharmacology andToxicology, Faculty ofPharmacy, Mansoura University, Mansoura35516, Egypt
3 Department ofPathology, College ofMedicine, Taibah University, Al-MadinahAl-Munawwarah30001, SaudiArabia
4 Department ofPathology, Faculty ofMedicine, Menoua University, Menoua, Egypt
5 Cardiology Unit, Department ofPediatrics, College ofMedicine, Taibah University, Al-MadinahAl-Munawwarah30001, SaudiArabia
Received: 21 October 2016 / Accepted: 26 December 2016 / Published online: 27 January 2017 Springer-Verlag Berlin Heidelberg 2017
diminished superoxide dismutase activity and glutathione content in heart tissue. Additionally, CP-induced overexpression of toll-like receptors-4 (TLR-4) and nuclear factor kappa-B (NF-B) accompanied by overproduction of inammatory cytokines (TNF-, NO). CP activated cardiomyocyte apoptosis as it increased apoptosis parameters (Bax and caspase-3) and decreased anti-apoptotic marker (Bcl-2). On the other hand, MP treatment attenuated all of the measured parameters of CP-induced cardiotoxicity.MP counteracted CP-induced oxidative stress and suppressed TLR-4 and NF-B overexpression. Also, levels of cytokines and apoptotic markers were declined while Bcl-2 was elevated in MP treated animals.
Conclusions MP may serve as a new cardioprotective candidate. The cardioprotective eects of MP may be attributed to its ability to suppress oxidative stress and interrupt TLR4/NF-B signaling pathway with subsequent amelioration of apoptosis.
Keywords Heart Cyclophosphamide Methyl palmitate Oxidative stress Nuclear factor kappa-BApoptosis
Introduction
Cyclophosphamide (CP) is a potent alkylating agent that is...