Key result
Doxorubicin administration significantly increased intracellular total, essential, and branched-chain amino acids in skeletal muscle compared to control (P<0.05), indicating a net increase in protein degradation.
p-value: p=<0.05
Doxorubicin administration significantly increases intracellular total, essential, and branched-chain amino acids in skeletal muscle, suggesting a net increase in protein degradation.
May signal doxorubicin-induced muscle catabolism in animals; leaves open relevance to human chemotherapy cachexia.
Skeletal muscle (SM) health and integrity is dependent on the dynamic balance between protein synthesis and degradation, and central to this process is the availability of amino acids (AA) in the amino pool. While Doxorubicin (DOX) remains one of the most widely used chemotherapeutic agents for the treatment of solid and hematological malignancies, little is known of the effect of the drug on SM, particularly its effect on the availability of amino acids in the tissue. The purpose of this study was to examine the effect of DOX administration on vascular, interstitial and intracellular concentrations of AA in SM of the rat up to 8 days after the administration of a 1.5 or 4.5 mg/kg i.p. dose of DOX. In the plasma, total amino acids (TAA) were significantly increased compared to control where greater (P<0.05) concentrations were observed following the 1.5 mg/kg dose compared to the 4.5 mg/kg dose. Compared to control, the 1.5 mg/kg dose resulted in an increase (P<0.05) in interstitial TAA whereas the 4.5 mg/kg resulted in a sustained decrease (P<0.05). Intracellular TAA, essential amino acids (EAA) and branched-chain amino acids (BCAA) where significantly increased in each muscle group analyzed, following the 1.5 and 4.5 mg/kg doses compared to control. This study provides important insight into the amino acid response following DOX chemotherapy and presents a substantial foundation for future studies focused on reducing SM damage and recovery by targeting amino acid metabolism.
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Fabris et al. (2018) studied Healthy (Animal Model) (n=106). Doxorubicin vs. Sham injection of saline solution was evaluated on Intracellular, interstitial, and vascular concentrations of amino acids in skeletal muscle (p=<0.05). Doxorubicin administration significantly increased intracellular total, essential, and branched-chain amino acids in skeletal muscle compared to control (P<0.05), indicating a net increase in protein degradation.
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