Endurance exercise training preserves cardiac function in rats receiving doxorubicin and the HER-2 inhibitor GW2974.
OBJECTIVE
To determine if endurance exercise training performed prior to administration of the anticancer drugs DOX and GW2974 would be cardioprotective.


METHODS
Rats remained sedentary or exercise trained for 10 weeks. Following the exercise or sedentary period, rats were randomly assigned to treatment groups. Rats in sedentary and exercise groups received saline or a combination of 10 mg/kg DOX and 30 mg/kg GW2974. Cardiac function was assessed 2, 5, or 10 days following treatments.


RESULTS
Sedentary animals receiving DOX/GW2974 experienced significant cardiac dysfunction. At 2-, 5-, and 10-days post, cardiac function in trained, drug-treated animals was significantly preserved. Additionally, animals exercised prior to DOX/GW2974 injections had significantly lower levels of myocardial lipid peroxidation and caspase-3 and -8 activities compared to their sedentary counterparts.


CONCLUSIONS
Exercise training protected against the cardiac dysfunction associated with DOX/GW2974 administration and may be related to an inhibition in apoptotic signaling.
Department of Health, Physical Education, and Recreation, Wright State University, Dayton, OH 45435, USA.
Karen Y
KY
Wonders
David S
DS
Hydock
Stephanie
S
Greufe
Carole M
CM
Schneider
Reid
R
Hayward
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D004317:Doxorubicin / Q000009:adverse effects* / Q000494:pharmacology; D005081:Exercise Therapy / Q000379:methods*; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011799:Quinazolines / Q000009:adverse effects* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D017725:Ventricular Pressure / Q000502:physiology
D000970:Antineoplastic Agents; C506645:GW2974; D011799:Quinazolines; D008315:Malondialdehyde; D004317:Doxorubicin; C505528:Casp8 protein, rat; D053148:Caspase 3; D053181:Caspase 8