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The Dose‐Related Effects of Doxorubicin Chemotherapy on Interstitial Amino Acid Concentrations in Skeletal Muscle
Author(s) -
MacLean David,
Fabris Sergio
Publication year - 2018
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.2018.32.1_supplement.536.14
Subject(s) - microdialysis , amino acid , interstitial space , doxorubicin , pharmacology , chemistry , skeletal muscle , saline , metabolism , chemotherapy , medicine , extracellular , biochemistry
Doxorubicin (DOX) is a frontline anticancer therapeutic which has proven effective in the treatment of various cancers. However, very little is known regarding the effect that DOX has on SM metabolism, specifically its influence on interstitial amino acid (AA) concentrations. In SM, the interstitial space represents an important active compartment located between the vasculature and the tissue and it has been shown to play a functional role in the regulation and integration of various metabolic substances. The purpose of the current study was to determine the effect of DOX on interstitial AA concentrations in SM. Rats received a 1.5 or 4.5 mg/kg dose of DOX i.p. and grouped into endpoints every 24 hrs up to 192 hrs. A control group was administered a sham i.p. injection of saline. Total amino acids (TAA), essential amino acids (EAA) and branched‐chain amino acids (BCAA) were quantified in the interstitial space. The administration of DOX resulted in a dose‐related difference in interstitial AA. The 1.5 mg/kg dose resulted in a transient increase (P<0.05) in TAA, EAA and BCAA from 24–96 hrs as compared to control. Contrarily, TAA, EAA and BCAA decreased (P<0.05) 24–192 hours following the administration of 4.5 mg/kg DOX as compared to control. This study by way of the microdialysis technique, represents the first time that amino acid concentrations have been quantified in the interstitial space following the administration of a chemotherapeutic drug. In addition, the possibility of a dose‐related effect of DOX on amino acid transport mechanisms from the skeletal muscle compartment into the interstitium/vasculature is of particular interest as this may represent a regulatory mechanism that has not previously been considered. Support or Funding Information Supported by NOSMFA This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .