title: Effects of local irradiation combined with sunitinib on early remodeling, mitochondria, and oxidative stress in the rat heart.
abstract: Thoracic (chemo)radiation therapy is increasingly administered with tyrosine kinase inhibitors (TKI). While TKI have adverse effects on the heart, it is unknown whether combination with other cancer therapies causes enhanced toxicity. We used an animal model to investigate whether radiation and sunitinib interact in their effects on the heart.
  
  
  
  Male Sprague-Dawley rats received local heart irradiation (9Gy per day, 5days). Oral sunitinib (8 or 15mg/kg bodyweight per day) started on day 1 of irradiation and continued for 2weeks. Cardiac function was examined with echocardiography. Cardiac remodeling, cell death, left ventricular (LV) oxidative stress markers, mitochondrial morphology and mitochondrial permeability transition pore (mPTP) opening were assessed.
  
  
  
  Cardiac diameter, stroke volume, and LV volume, mass and anterior wall thickness increased in time, but only in the vehicle group. Sunitinib reduced LV inner diameter and volume in systole, which were counteracted by radiation. Sunitinib and radiation showed enhanced effects on mitochondrial morphology and mPTP opening, but not on cardiac troponin I, mast cell numbers or markers of oxidative stress.
  
  
  
  This study found no early enhanced effects of radiation and sunitinib on cardiac function or structure. Long-term effects remain to be determined.
authors.affiliation: University of Arkansas for Medical Sciences, Department of Pharmaceutical Sciences, Division of Radiation Health, Little Rock, United States.
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Sridharan
authors.affiliation: Oakwood University, Huntsville, United States.
authors.forename: Chanice J
authors.initials: CJ
authors.lastname: Thomas
authors.affiliation: University of Arkansas for Medical Sciences, Department of Pharmaceutical Sciences, Division of Radiation Health, Little Rock, United States.
authors.forename: Maohua
authors.initials: M
authors.lastname: Cao
authors.affiliation: University of Arkansas for Medical Sciences, Department of Pediatrics, Little Rock, United States.
authors.forename: Stepan B
authors.initials: SB
authors.lastname: Melnyk
authors.affiliation: University of Arkansas for Medical Sciences, Department of Pediatrics, Little Rock, United States.
authors.forename: Oleksandra
authors.initials: O
authors.lastname: Pavliv
authors.affiliation: Veterans Affairs Boston Healthcare System, Department of Medicine, United States; Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, United States.
authors.forename: Jacob
authors.initials: J
authors.lastname: Joseph
authors.affiliation: University of Arkansas for Medical Sciences, Department of Pharmacology and Toxicology, Little Rock, United States.
authors.forename: Sharda P
authors.initials: SP
authors.lastname: Singh
authors.affiliation: University of Arkansas for Medical Sciences, Department of Radiation Oncology, Little Rock, United States.
authors.forename: Sunil
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, United States.
authors.forename: Eduardo G
authors.initials: EG
authors.lastname: Moros
authors.affiliation: University of Arkansas for Medical Sciences, Department of Pharmaceutical Sciences, Division of Radiation Health, Little Rock, United States. Electronic address: mboerma@uams.edu.
authors.forename: Marjan
authors.initials: M
authors.lastname: Boerma
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000528:radiation effects; D000083162:Mitochondrial Permeability Transition Pore; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077210:Sunitinib; D020257:Ventricular Remodeling / Q000187:drug effects / Q000528:radiation effects
chemical_list: D007211:Indoles; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011758:Pyrroles; D000077210:Sunitinib
keywords: Heart; Ionizing radiation; Mitochondria; Oxidative stress; Sunitinib