Short-term exercise training attenuates acute doxorubicin cardiotoxicity

Area of Science:

• Cardiology
• Exercise Physiology
• Pharmacology

Background:

• Doxorubicin (DOX) is a vital chemotherapy drug, but its use is limited by dose-dependent cardiotoxicity.
• While chronic exercise is known to protect against DOX-induced heart damage, the effects of short-term exercise remain less understood.

Purpose of the Study:

• To investigate if short-term wheel running (WR) and treadmill exercise (TM) can attenuate cardiac dysfunction induced by DOX.
• To explore potential mechanisms, such as changes in calcium handling, underlying any protective effects of exercise.

Main Methods:

• Male Sprague-Dawley rats underwent a 5-day voluntary wheel running or treadmill exercise regimen.
• Animals then received either 10 or 15 mg/kg of DOX or saline.
• Cardiac function was assessed 5 days post-DOX exposure, and left ventricular SERCA2a protein expression was quantified via Western immunoblotting.

Main Results:

• Both WR and TM exercise preconditioning significantly attenuated DOX-induced in vivo and ex vivo cardiac dysfunction.
• Exercise protocols preserved fractional shortening and left ventricular developed pressure compared to sedentary DOX-treated rats.
• Left ventricular sarcoendoplasmic reticulum calcium-ATPase 2a (SERCA2a) expression was maintained in exercise-preconditioned groups.

Conclusions:

• Short-term exercise prior to doxorubicin treatment can serve as a valuable adjuvant therapy to mitigate acute cardiotoxicity.
• The preservation of cardiac function may be partly attributed to exercise-induced maintenance of calcium handling in cardiomyocytes.