title: Exercise mitigates cardiac doxorubicin accumulation and preserves function in the rat.
abstract: OBJECTIVE
  Doxorubicin (DOX) is an effective antineoplastic agent with well-characterized cardiotoxic effects. Although exercise has been shown to protect against DOX cardiotoxicity, a clear and concise mechanism to explain its cardioprotective effects is lacking. The purpose of this study was to determine if exercise training reduces cardiac DOX accumulation, thereby providing a possible mechanism to explain the cardioprotective effects of exercise against DOX toxicity.
  
  
  METHODS
  Sprague-Dawley rats were randomly assigned to 1 of 3 primary experimental groups: sedentary (n = 77), wheel running (n = 65), or treadmill (n = 65). Animals in wheel running and treadmill groups completed 10 weeks of exercise before DOX treatment. DOX was administered 24 hours after the last training session as a bolus intraperitoneal injection at 10 mg/kg. Subgroups of rats from each primary group were killed at 1, 3, 5, 7, and 9 days after DOX exposure to assess cardiac function and DOX accumulation.
  
  
  RESULTS
  Ten weeks of exercise preconditioning reduced myocardial DOX accumulation, and this reduction in accumulation was associated with preserved cardiac function.
  
  
  CONCLUSIONS
  These data suggest that the cardioprotective effects of exercise against DOX-induced injury may be due, in part, to a reduction in myocardial DOX accumulation.
authors: *School of Sport and Exercise Science and the Rocky Mountain Cancer Rehabilitation Institute, University of Northern Colorado, Greeley, CO; †Department of Exercise and Rehabilitative Sciences, Slippery Rock University, Slippery Rock, PA; and ‡Department of Athletics, National Taiwan University, Taipei, Taiwan.
authors: Brock T
authors: BT
authors: Jensen
authors: Chia-Ying
authors: CY
authors: Lien
authors: David S
authors: DS
authors: Hydock
authors: Carole M
authors: CM
authors: Schneider
authors: Reid
authors: R
authors: Hayward
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics*; D001522:Behavior, Animal; D054715:Cardiotoxins / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics*; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000517:prevention & control*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics*; D004452:Echocardiography; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D009043:Motor Activity; D009206:Myocardium / Q000737:chemistry*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; D054715:Cardiotoxins; D004317:Doxorubicin