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Aims: To examine the pretreatment effects of regular aerobic training on the IGF system (IGF-I, IGFBP-3 and IGF/IGFBP) and doxorubicin(DOX) induced hepatotoxicity in rats., Materials and Methods: Forty-eight male rats were divided into groups:(1) control+placebo (2)control+DOX10 mg.kg-1 (3)control+DOX20 mg.kg-1 (4) training+placebo (5) training+DOX10 mg.kg-1 (6) training+DOX20 mg.kg-1. Hepatotoxicity was induced by DOX with dosages of 10 and 20 mg.kg-1. The rats in groups 4, 5 and 6 performed treadmill running of 25-54 min/day and 15-20 m/min, 5 days/wk for 6 wks. At the end of the aerobic training protocol, rats in the 1 and 4 groups, in the 2 and 5 groups and in the 3 and 6 groups received saline solution, DOX10 mg.kg-1 and DOX20 mg.kg-1, respectively., Results: Administration of DOX20 mg.kg-1 caused a significant increase in IGF-1 and IGF-1/IGFBP-3, an insignificant decrease in IGFBP-3, as compared to the control+placebo group. However, after six weeks of aerobic training and DOX treatment with 10mg.kg-1 and or/ 20mg.kg-1 an insignificant decrease in IGF-1, an insignificant increase in IGFBP-3 and a significant decrease in IGF-1/IGFBP-3 were detected, in comparison to C+DOX10 and C+DOX20., Conclusions: Hepatotoxicity of doxorubicin is dose-dependent and pretreatment with regular aerobic training may improve DOX-induced hepatotoxicity by up-regulation of IGFBP3.

Background: Doxorubicin is an anthracycline antibiotic commonly used to treat a variety of cancers as a most effective antitumor. However, its clinical use is associated with the toxic effects in numerous healthy tissues. Here we investigated the pretreatment effect of regular aerobic exercise on oxidative stress in rats acutely exposed to DOX-induced hepatotoxicity., Materials and Methods: Forty-eight Wistar male rats were randomly divided into 2 groups: control and training. The training protocol included treadmill running between 25 to 54 min/day and 15 to 20 m/min, 5 days/week for 6 weeks. At the end of the exercise training protocol, rats from the control and trained groups were again randomly separated into 3 subgroups: DOX 10 mg/kg, DOX 20 mg/kg and saline. All treatments were carried 24 h after the last exercise bout and animals were sacrificed 24 h after DOX and saline injections., Results: Administration of DOX (10 and 20 mg.kg-1) resulted in imbalance in biomarkers related to oxidants and antioxidants in liver tissue, as compared to control groups. Six weeks of pretreatment training led to a significant increase in nitric oxide (NO), superoxide dismutase (SOD) and glutathione peroxidase (GPX) as compared to the control+DOX 10 mg/kg group. Training before DOX 20 mg/kg administration also led to a significant increase in NO and SOD, and a significant decrease in malondialdehyde (MDA). In addition, there was a significant difference between DOX 10 mg/kg and DOX 20 mg/kg treatments in MDA levels, only., Conclusions: The results of the present study indicate that pretreatment with aerobic exercise induces positive adaptations and has a potential protective effect against doxorubicin (DOX)-induced hepatotoxicity with doses of 10 and 20 mg.kg.

Objective: The purpose of this study was to determine pretreatment effects of moderate-term endurance training before the various dosages (10 and 20 mg.kg(-1)) of DOX on a heat shock protein (HSP70 kda) and cardiotoxicity in heart tissue., Methods: Forty-eight male rats were randomly assigned to nontraining (NT) and training (T) groups and three subgroups; DOX10 mg.kg(-1) and DOX20 mg.kg(-1) and saline treatment. The training program included treadmill running between 25-39 min/day and 15-17 m/min, 5 days/wk for 3 wk., Result: DOX administration, in particularly with 20 mg.kg(-1), caused up-regulation of oxidants and cardiac damage (MDA, CK, CPK-MB and CK/ CPK-MB) and down-regulation of cardioprotection (HSP70, SOD) markers, as compared to NT+saline group. Pretreatment effect of treadmill running endurance exercise in the presence of DOX with 10 mg.kg(-1) caused a significant increase in HSP70, SOD and a significant decrease in MDA and insignificant decrease in CK, CPK-MB and CK/CPK-MB, in comparisonT+DOX10 with NT+DOX10 group. However, there was no significant difference between T+DOX10 mg.kg(-1) and T+DOX20 mg.kg(-1) in the aforesaid markers., Conclusion: Dox-induced cardiotoxicity is related to oxidative stress. Our study suggests that pretreatment with endurance exercise may be considered as a potentially useful strategy to improve myocardial tolerance against single dose DOX-induced oxidative damage.

Background and Objective: Cardiotoxicity and oxidative stress is a life-threatening side effect of doxorubicin (DOX). We investigate the effects of short-term exercise as therapeutic tool for improvement of cardioprotection against DOX-induced cardiotoxicity in the rat., Methods: Wistar males (weighing 257 ± 28 g) were divided into six groups: (1) control+placebo (2) control+DOX 10 mg.kg(-1) (3) control+DOX 20mg.kg(-1) (4) training+placebo (5) training+ DOX10 mg.kg(-1) (6) training+DOX 20mg.kg(-1). Cardiotoxicity was induced by DOX (10 and 20 mg.kg(-1)). The rats in groups 4, 5 and 6 experienced treadmill running of 25 to 39 min.day(-1) and 15 to 17 m.min(-1), 5 days/ wk for 3 wk. At the end of the endurance training program, rats in the 1 and 4 groups, in the 2 and 5 groups and in the 3 and 6 groups received saline solution, DOX 10 mg.kg(-1) and DOX 20 mg.kg(-1), respectively., Result: DOX administration (10 and 20 mg.kg(-1)) caused significant increase in MDA and Apelin, an insignificant increase in NO and a significant decrease in SOD, as compared to the C+P group. Three weeks of the pretreatment endurance exercise resulted in a significant increase of Apelin and SOD, an insignificant increase of NO and an insignificant decrease of MDA, as compared to the C+P group. Furthermore, after three weeks of endurance training and DOX treatment with 10mg.kg(-1) and 20mg.kg(-1), a significant increase in apelin and SOD, and a significant decrease in MDA were detected in comparison to C+DOX10 and/or C+DOX20 groups. There was a significant difference between DOX10 mg.kg(-1) and DOX20 mg.kg(-1) treatments in MDA levels only., Conclusion: Pretreatment exercise may improve myocardial tolerance to DOX-induced cardiotoxicity by inhibition of oxidative stress and up- regulation of antioxidants in heart tissue.