Chicco et al.99 Ascensão A, Magalhães J, Soares JM, Ferreira R, Neuparth MJ, Marques F, et al. Moderate endurance training prevents doxorubicin-induced in vivo mitochondriopathy and reduces development of cardiac apoptosis. Am J Physiol Heart Circ Physiol. 2005;289(2):H722-31.
|
Female rats (n=28) |
10 µ DOX for 60 min |
Voluntary 8 weeks before DOX |
Resistance against cardiac dysfunction and oxidative damage, increase in heat shock protein (HSP72) |
Ascensão et al.1010 Chicco AJ, Hydock DS, Schneider CM, Hayward R. Low-intensity exercise training during doxorubicin treatment protects against cardiotoxicity. J Appl Physiol (1985). 2006;100(2):519-27.
|
Male rats (n=40) |
20 mg/kg single dose |
Treadmill running 60 min/day, 5 days/week, 14 weeks before DOX |
Maintenance of homeostasis, increase in mitochondrial defenses and reduced oxidative damage. |
Chicco et al.1111 Ascensão A, Magalhães J, Soares J, Ferreira R, Neuparth M, Marques F, et al. Endurance training attenuates doxorubicin-induced cardiac oxidative damage in mice. Int J Cardiol. 2005;100(3):451-60.
|
Male rats (n=28) |
2,5 mg/kg 3 x / week for 2 weeks (15mg/kg) |
Treadmill 60 min/day, 5 days/week, 2 weeks during DOX treatment |
Attenuated left ventricular dysfunction and apoptotic signal activation. |
Ascensão et al.1212 Chicco AJ, Schneider CM, Hayward R. Exercise training attenuates acute doxorubicin-induced cardiac dysfunction. J Cardiovasc Pharmacol. 2006;47(2):182-9.
|
Male rats (n=44) |
20 mg/kg single dose |
Swimming 1h/day, 5 days/week for 14 weeks before treatment |
Increase in cardiac muscle tolerance to DOX, with increased response of antioxidant system. |
Chicco et al.1313 Wonders KY, Hydock DS, Schneider CM, Hayward R. Acute exercise protects against doxorubicin cardiotoxicity. Integr Cancer Ther. 2008;7(3):147-54.
|
Male rats (n=42) |
15 mg/kg single dose |
Treadmill 1h/day, 5 days/week for 14 weeks before treatment |
Attenuated cardiac dysfunction and lipid peroxidation, and increased HSP72. |
Wonders et al.1414 Hydock DS, Lien CY, Schneider CM, Hayward R. Exercise preconditioning protects against doxorubicin-induced cardiac dysfunction. Med Sci Sports Exerc. 2008;40(5):808-17.
|
Male rats (n=not specified) |
15 mg/kg single dose |
Treadmill 1 hour on a single day before DOX |
Prevented cardiac dysfunction. |
Hydock et al.1515 Kavazis AN, Smuder AJ, Min K, Tümer N, Powers SK. Short-term exercise training protects against doxorubicin-induced cardiac moticondrial damage independent of HSP72. Am J Physiol Heart Circ Physiol. 2010;299(5):H1515-24.
|
Male rats (n=147) |
10 mg/kg single dose |
Voluntary and treadmill, 1h/day, 5 days/week for 8 weeks before treatment |
Protected against cardiotoxicity for up to 10 days, preserving cardiac function and myosin heavy chain expression. |
Wonders et al.1616 Ascensão A, Lumini-Oliveira J, Machado NG, Ferreira RM, Gonçalves IO, Moreira AC, et al. Acute exercise protects against calcium-induced cardiac mitochondrial permeability transition pore opening in doxorubicin-treated rats. Clin Sci (Lond). 2011;120(1):37-49.
|
Female rats (n=45) |
DOX 10mg/kg single dose + GW2974 |
Treadmill 60 min/day, 5 days/week for 8 weeks before treatment |
Preserved cardiac function and decreased apoptosis signaling and lipid peroxidation. |
Kavazis et al.1717 Hydock DS, Lien CY, Jensen BT, Schneider CM, Hayward R. Exercise preconditioning provides long-term protection against early chronic doxorubicin cardiotoxicity. Integr Cancer Ther. 2011;10(1):47-57.
|
Male rats (n=28) |
20 mg/kg single dose |
Treadmill 60 min/day, 5 days/week for one week |
Attenuated mitochondrial damage and preserved the antioxidant metabolism. |
Ascensão et al.1818 Ashraf J, Roshan VD. Is short-term exercise a therapeutic tool for improvement of cardioprotection against DOX-induced cardiotoxicity? An experimental controlled protocol in rats. Asian Pac J Cancer Prev. 2012;13(8):4025-30.
|
Male rats (n=20) |
20 mg/kg single dose |
Treadmill, 1hour on a single day before DOX |
Prevented the decrease in mitochondrial function and antioxidant metabolism |
Hydock et al.1919 Shirinbayan V, Roshan VD. Pretreatment effect of running exercise on HSP70 and DOX-induced cardiotoxicity. Asian Pac J Cancer Prev. 2012;13(11):5849-55.
|
Female rats (n=49) |
15 mg/kg single dose + goserelin acetate |
Treadmill 60 min/day, for 8 weeks during treatment |
Attenuated dysfunction of left ventricle and mitral and aortic valves. |
Hydock et al.2020 Martins RA, Minari AL, Chaves MD, Santos RW, Barbisan LF, Ribeiro DA. Exercise preconditioning modulates genotoxicity induced by doxorubicin in multiple organs of rats. Cell Biochem Funct. 2012;30(4):293-6.
|
Male rats (n=94) |
1 mg/kg/day for 10 days (10 mg/kg) |
Voluntary and treadmill, 1h/day, 5 days/week for 8 weeks before treatment |
Prevented cardiac dysfunction and expression of myosin heavy chain even after 1 month of treatment. |
Hornsby et al 2121 Smuder AJ, Kavazis AN, Min K, Powers SK. Doxorubicin-induced markers of myocardial autophagic signaling in sedentary and exercise trained animals. J Appl Physiol (1985). 2013;115(2):176-85.
|
Humans (n=20) |
60 mg/m2 + 600 mg/m2 cyclophosphamide One dose every 3 weeks for 12 weeks. |
Cycle ergometry 60 min/day, 3 days/week for 12 weeks during treatment. |
Attenuated the increase in natriuretic peptides. |
Hayward et al.77 Hayward R, Lyen CY, Jensen BT, Hydock DS, Schneider CM. Exercise training mitigates anthracycline-induced chronic cardiotoxicity in a juvenile rat model. Pediatr Blood Cancer. 2012;59(1):149-54.
|
Rat pups (n=64) |
2 mg/kg/day during 12 days (14 mg/kg) |
Voluntary for 10 weeks during and after treatment |
Preserved cardiac growth curve and body mass, and attenuated cardiac dysfunction. |
Ashrafi and Roshan2222 Marques-Aleixo I, Santos-Alves E, Mariani D, Rizo-Roca D, Padrão AI, Rocha-Rodrigues S, et al. Physical exercise prior and during treatment reduces sub-chronic doxorubicin-induced mitochondrial toxicity and oxidative stress. Mitochondrion. 2015;20:22-33.
|
Male rats (n=48) |
10 mg/kg, 20 mg/kg |
Treadmill warm up + 39 min/day, 5 days/week for 4 weeks before DOX |
Protected against oxidative damage and preserved the balance between production and catabolism of oxidative agents oxidative. |
Shirinbayan and Roshan 2323 Chicco AJ, Schneider CM, Hayward R. Voluntary exercise protects against acute doxorubicin cardiotoxicity in the isolated perfused rat heart. Am J Physiol Regul Integr Comp Physiol. 2005;289(2):R424-31.
|
Male rats (n=48) |
10mg/kg, 20mg/kg |
Treadmill warm up + 39 min/day, 5 days/week for 4 weeks before DOX |
Decrease the risk of cardiac disturbance and preserved the antioxidant systems. |
Martins et al.2424 Wonders KY, Hydock DS, Greufe S, Schneider CM, Hayward R. Endurance exercise training preserves cardiac function in rats receiving doxorubicin and the HER-2 inhibitor GW2974. Cancer Chemother Pharmacol. 2009;64(6):1105-13.
|
Male rats (n=12) |
15 mg/kg single dose |
Swimming 60 min/day, 5 days/week, for over 21 days of treatment |
Protection to cardiac cell DNA. |
Smuder et al.2525 Hydock DS, Parry TL, Jensen BT, Lien CY, Schneider CM, Hayward R. Effects of endurance training on combined goserelin acetate and doxorubicin treatment-induced cardiac dysfunction. Cancer Chemother Pharmacol. 2011;68(3):685-92.
|
Male rats (n=24) |
20 mg/kg single dose |
Treadmill 60 min/day, 5 days/week for one week before treatment |
Inhibited the increase in lysosomal autophagy signaling. |
Jensen et al.2626 Jensen BT, Lien CY, Hydock DS, Schneider CM, Hayward R. Exercise mitigates cardiac doxorubicin accumulation and preserves function in the rat. J Cardiovasc Pharmacol. 2013;62(3):263-9.
|
Female rats (n=77) |
10 mg/kg single dose |
Voluntary and treadmill, 1h/day, 5 days/week for 10 weeks before treatment |
Reduced the time and the level of myocardial DOX accumulation. |
Marques-Aleixo et al.2727 Hornsby WE, Douglas PS, West MJ, Kenjale AA, Lane AR, Schwitzer ER, et al. Safety and efficacy of aerobic training in operable breast cancer patients receiving neoadjuvant chemotherapy: a phase II randomized trial. Acta Oncol. 2014;53(1):65-74.
|
Male rats (n=36) |
2 mg/kg/ week for 7 weeks |
Voluntary and treadmill 1 h/day, 5 days/week for 12 weeks |
Improved mitochondrial bioenergetic fitness and prevented the damage caused by oxidative stress. |