Pretreatment effects of regular aerobic training on the IGF system and hepatotoxicity induced by doxorubicin in rats.

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.