The Protective Effect of Regular Aerobic Training on Doxorubicin-Induced Hepatotoxicity in Rats: The Insulin-Like Growth Factor System

Background: The liver plays a central role in insulin-like growth factor (IGF) system homeostasis. We examine the protective aerobic training on the IGF system following doxorubicin (DOX) induced hepatotoxicity. Materials and Methods: In this experimental study 48 Wistar male rats (weighing 257±28 g) were divided into 6 groups: (1) control+placebo (2) control+DOX 10 mg/kg (3) control+DOX 20 mg/kg (4) training+placebo (5) training+DOX 10 mg/kg (6) training+DOX 20 mg/kg. Hepatotoxicity was induced by DOX (10 and 20 mg/kg). Rats in the 4, 5 and 6 groups performed treadmill running of 25 to 54 min/day and 15 to 20 m/min, 5 days/week for 3 weeks. Results: While, DOX 10 mg/kg administration result in an insignificant increase in IGF-1 and IGF-1/IGFBP-3 and an insignificant decrease in IGFBP-3, DOX 20 mg/kg administration caused a significant increase in IGF-1 and IGF-1/IGFBP-3, an insignificant decrease in IGFBP-3, as compared to the group 1. Three weeks of the endurance exercise resulted in a significant decrease of IGF-1 and IGF-1/IGFBP-3 levels, and significant increase in IGFBP-3, as compared to the group 1. Furthermore, after 3 weeks endurance training and DOX treatment with 10 mg/kg 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 group 2. Conclusion: DOX hepatotoxicity is dose-dependent, acute administration of DOX 20 mg/kg caused an imbalance in the IGF system and protective aerobic training may improve DOX-induced hepatotoxicity by up-regulation of IGFBP3.