title: Modulation of cyclophosphamide-induced cardiotoxicity by methyl palmitate.
abstract: 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.
  
  
  
  Adult male Wistar rats were divided into four groups. The first 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 different dose levels (300, 400 mg/kg) for 10 days before and 7 days after CP single injection.
  
  
  
  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 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-κB) accompanied by overproduction of inflammatory cytokines (TNF-α, 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-κB overexpression. Also, levels of cytokines and apoptotic markers were declined while Bcl-2 was elevated in MP treated animals.
  
  
  
  MP may serve as a new cardioprotective candidate. The cardioprotective effects of MP may be attributed to its ability to suppress oxidative stress and interrupt TLR4/NF-κB signaling pathway with subsequent amelioration of apoptosis.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, P.O. Box 344, Al-Madinah Al-Munawwarah, 30001, Saudi Arabia. dinaagamy1@yahoo.com.|Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt. dinaagamy1@yahoo.com.
authors.forename: Dina S
authors.initials: DS
authors.lastname: El-Agamy
authors.affiliation: Department of Pathology, College of Medicine, Taibah University, Al-Madinah Al-Munawwarah, 30001, Saudi Arabia.|Department of Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Elkablawy
authors.affiliation: Cardiology Unit, Department of Pediatrics, College of Medicine, Taibah University, Al-Madinah Al-Munawwarah, 30001, Saudi Arabia.
authors.forename: Hany M
authors.initials: HM
authors.lastname: Abo-Haded
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D066126:Cardiotoxicity / Q000188:drug therapy; D003520:Cyclophosphamide / Q000633:toxicity*; D004562:Electrocardiography / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D010168:Palmitates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D051197:Toll-Like Receptor 4 / Q000235:genetics
chemical_list: D016328:NF-kappa B; D010168:Palmitates; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D003520:Cyclophosphamide; C019012:methyl palmitate
keywords: Apoptosis; Cyclophosphamide; Heart; Methyl palmitate; Nuclear factor kappa-B; Oxidative stress