In vivo Skeletal Muscle Function and Doxorubicin Treatment in the Rat

Abstract

The chemotherapy drug doxorubicin (DOX) has been shown to cause skeletal muscle dysfunction when measured ex vivo, but little is known about the effects of DOX on in vivo skeletal muscle function. The aim of this study was to examine the effects of two different bolus DOX treatments on skeletal muscle function measured in vivo using a rat grip strength meter. Baseline grip strength was assessed prior to rats receiving intraperitoneal injections of 10 mg/kg DOX (DOX1), 15 mg/kg DOX (DOX2), or saline as a control (CON). Grip strength was then assessed daily for seven days. At baseline, no between group differences in grip strength were observed, but a between group difference was observed at day four with DOX2 having a lower grip strength than CON and DOX1. This reduced grip strength in DOX2 continued through day seven. DOX1 had reduced grip strength when compared to CON only at day six. These results suggest that DOX administration affects in vivo skeletal muscle function in a dose‐dependent manner. As such, this model provides a novel approach for analyzing DOX myotoxicity and interventions aimed at minimizing this side effect.