Endurance exercise attenuates cardiotoxicity induced by androgen deprivation and doxorubicin.
Doxorubicin (DOX) is associated with cardiac dysfunction and irreversible testicular damage. Androgen deprivation therapy (ADT) is administered prior to DOX treatment to preserve testicular function. However, ADT may exacerbate DOX-induced cardiac dysfunction. Exercise is cardioprotective, but the effects of exercise on cardiac function during combined ADT and DOX treatment are currently unknown. In this study, male Sprague-Dawley rats were randomly assigned to experimental groups: control (CON), ADT, DOX, or ADT+DOX. Animals received ADT or control implants on days 1 and 29 of the 56-day protocol. Animals remained sedentary (SED) or engaged in treadmill endurance exercise (TM) beginning on day 1. On day 15, the animals received DOX at 1 mg·(kg body mass)(-1)·d(-1) by intraperitoneal injection for 10 consecutive days, or an equivalent volume of saline. On day 57, cardiac function was assessed in vivo and ex vivo. Animals treated with DOX alone, or with combined ADT+DOX, showed significant (P < 0.05) reductions in left ventricular developed pressure (-21% and -27%), maximal rate of pressure development (-29% and -32%), and maximal rate of pressure decline (25% and 31%), respectively when compared with the sedentary control animals. Endurance exercise training attenuated (P > 0.05) cardiac dysfunction associated with combined ADT+DOX treatment, indicating that exercise during simultaneous ADT+DOX treatment is cardioprotective.
a School of Sport and Exercise Science, University of Northern Colorado, Greeley, CO 80639, USA.
Traci L
TL
Parry
David S
DS
Hydock
Brock T
BT
Jensen
Chia-Ying
CY
Lien
Carole M
CM
Schneider
Reid
R
Hayward
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D066126:Cardiotoxicity; D004317:Doxorubicin / Q000009:adverse effects*; D017273:Goserelin / Q000009:adverse effects*; D006331:Heart Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D007986:Luteinizing Hormone / Q000819:agonists*; D008297:Male; D018995:Myosin Heavy Chains / Q000378:metabolism; D010805:Physical Conditioning, Animal; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
D000728:Androgens; D000903:Antibiotics, Antineoplastic; D017273:Goserelin; D004317:Doxorubicin; D007986:Luteinizing Hormone; D018995:Myosin Heavy Chains