Premium
The differential accumulation of doxorubicin in the soleus and gastrocnemius muscle of the rat
Author(s) -
Fabris Sergio Antonio,
Chenard Pamela,
Anderson Lindsay,
MacLean David
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1152.12
Subject(s) - skeletal muscle , soleus muscle , chemistry , gastrocnemius muscle , endocrinology , doxorubicin , medicine , intracellular , chemotherapy , biochemistry
The purpose of the present study was to examine intramuscular (IM) doxorubicin (DOX) levels in the soleus (S) and gastrocnemius (G) muscles of Sprague‐Dawley rats following the administration of DOX (1.5 or 4.5 mg/kg). Muscles were collected at 24, 48, 72 and 192 hrs post injection. DOX concentrations were elevated (P<0.05) as compared to control at all time points. Following the 1.5 mg/kg dose, concentrations peaked in both muscles after 48 hrs, but were higher (P<0.05) in the S (1.47±0.46 nmol/g) as compared to the G (0.78±0.24 nmol/g). Similarly, DOX was higher (P<0.05) in the S (0.40±0.13 nmol/g) than the G (0.08±0.02 nmol/g) after 192 hours. The 4.5 mg/kg dose resulted in similar peak DOX concentrations in both the G (2.43±0.52 nmol/g) and the S (2.46±1.35 nmol/g), but this occurred sooner (48 hr) in the S as compared to the G (72 hrs). DOX levels were not different between muscle groups following 192 hrs. These data not only support the notion that DOX accumulates in skeletal muscle in a dose dependent manor, but clearly demonstrate that fiber type differences are a factor in the rate of accumulation and removal or degradation of intracellular DOX. These findings have clinical implications as skeletal muscle may be an important compartment for the sequestering of DOX from the circulation, effectively limiting its therapeutic impact. Supported by NSERC.