Effect of Pretreatment of Aerobic Training on Doxorubicin-induced Left Ventricular Apoptosis Gene Expression in Aging Model Rats

AbstractObjective: Aging can affect adaption of the heart tissue apoptotic system to aerobic exercise and induction of doxorubicin. Therefore, the aim of this study was to evaluate the effect of pretreatment of aerobic training on doxorubicin-induced left ventricular apoptosis gene expression in aging model rats.Methods: ۴۲ adult Wistar male rats were randomly assigned to ۶ groups of ۷ rats: control of young, control of aging, aging + saline, aging + doxorubicin, aging + aerobic exercise + saline and aging + aerobic exercise + doxorubicin. Aging was induced by intraperitoneal injection of D- galactose (۱۰۰mg/kg). The training protocol included treadmill running with a gradual increase between ۲۵min/day to ۵۴min/day and in velocity of ۱۵m/min to ۲۰m/min, ۵ days/week for ۶ weeks. During the two ultimate weeks of the training, animals underwent a ۱۵ day intraperitoneal (i.p.) doxorubicin regimen, receiving ۱ mg .kg−۱ of doxorubicin per day. The rats were sacrificed ۴۸ hours after the last training and injection session and part of the left ventricle was investigated by Real Time- PCR analysis to evaluate the expression of Bax and Bcl-۲ genes expression.Results: ANOVA revealed that doxorubicin injection induced a significant increase in expression of Bax and Bax/Bcl-۲ ratio and an insignificant decrease in Bcl-۲ gene expression. On the other hand, aerobic training before and during the induction of doxorubicin prevented the increase in Bax/Bcl-۲ ratio and the doxorubicin-induced decrease in Bcl-۲ gene expression.Conclusion: Due to the significant decrease in Bax/Bcl-۲ ratio in heart of the trained rats which were treated with doxorubicin, it can be concluded that aerobic exercise training prior to and during treatment with doxorubicin as a non-pharmacological strategy, probably protects cardiomyocytes from doxorubicin-induced apoptosis.

کلیدواژه ها:

Aerobic exercise ، Doxorubicin ، Cardiotoxicity ، Pre-treatment ، Heart apoptosis ، دوکسوروبیسین ، سمیت قلبی ، پیش درمان ، تمرین هوازی ، آپوپتوز قلب