The Effect of Doxorubicin Administration on Intramuscular BCAA Concentrations in the Rat

Abstract

The purpose of the present study was to examine the effect of Doxorubicin (DOX) administration on total intramuscular branch chained amino acids (BCAA) in the soleus (SOL) and white gastrocnemius (WG) of the rat following a single IP administration of 1.5 or 4.5 mg/kg DOX after 24, 48, 72, 96, 120, 144, 168 and 192 hrs. The administration of 1.5 mg/kg DOX did not cause significant changes in BCAA concentrations in the SOL or the WG. However the 4.5 mg/kg dose resulted in a decrease (P<0.05) of BCAA in the SOL 24, 168 and 192 hours (105±8, 120±10 and 155±15 µmol/kg dw, respectively) post injection compared to control (304±34 µmol/kg dw). Similarly, BCAA significantly decreased in the WG 24, 144, 168 and 192 hours (93±8, 123±10, 107±11 and 154±19 µmol/kg dw, respectively) after the administration of the 4.5 mg/kg dose compared to control (317±44 µmol/kg dw). BCAA concentrations in the SOL were decreased (P<0.05) following the 4.5 mg/kg dose, when compared to 1.5 mg/kg, after 24 (224±3 %), 72 (138±3 %), 144 (154±2 %), 168 (183±5 %) and 192 hours (149±6 %). Likewise, BCAA concentrations in the WG were decreased (P<0.05) following the administration of 4.5 mg/kg DOX after 24 (288±8 %), 144 (224±1 %), 168 (239±8 %) and 192 hours (151±11 %) when compared to the 1.5 mg/kg dose. There were no consistent differences when comparing between muscle types. These data represent, for the first time, alterations in BCAA in the skeletal muscle as a function of DOX administration. This presents a significant clinical implication as a single administration of DOX effectively reduces BCAA which promotes muscle wasting and a poor clinical outcome. Supported by NSERC.