Current Highlight from March 11, 2016
Early Doxorubicin-Induced Metabolomic Changes in Heart and Plasma
NCTR scientists measured significant early alterations in the levels of multiple metabolites in blood and heart tissue from mice treated with doxorubicin (DOX). The following were significantly altered in plasma from mice that received a cumulative DOX dose of 6 mg/kg (administered at 3 mg/kg/week) before cardiac troponin and histopathological cardiac injury was detected at the 18 and 24 mg/kg cumulative doses, respectively:
- 16 amino acids
- 2 biogenic amines
- 16 acylcarnitines
- lactate
- succinate
Additionally, 18 amino acids and 4 biogenic amines were altered in heart tissue at the same cumulative dose level. These early metabolic changes observed in plasma during the initial stages of DOX-induced cardiac injury could be candidates for early biomarkers of cardiotoxicity. DOX is an effective chemotherapeutic that is limited by a life-time dose due to cardiotoxicity; and early biomarkers of cardiotoxicity could have clinical applications for individualized treatment. A manuscript describing the study is now available at Journal of Applied Toxicology.
For additional information, please contact Laura Schnackenberg, Ph.D., Biomarkers and Alternative Models Branch, Division of Systems Biology, FDA/NCTR.
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