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Eur J Cancer Clin Oncol. 1988 Jul;24(7):1123-31.

Cytofluorescence localization and disposition of doxorubicin and doxorubicinol in rat cardiac tissue.

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Institute of Medical Pharmacology, University of Pisa, Italy.


The localization of cardiac cytofluorescence and tissue levels of doxorubicin (DXR) and doxorubicinol (DXR-ol) were studied in rats treated with a single (9 mg/kg: 1-day study) or 3 weekly doses (3 mg/kg: 7-week study) of the compounds. A striking orange-red fluorescence was observed in cardiac cell nuclei from DXR 1-day rats, whilst heart cells from DXR-ol 1-day rats displayed a faint, diffuse fluorescence. Neither cardiac tissue from DXR nor from DXR-ol 7-week animals showed any drug-specific fluorescence. HPLC assay showed that in DXR 1-day rats the drug was concentrated in the heart, which also contained the endogenously produced DXR-ol. Plasma levels of DXR-ol were initially high in DXR-ol 1-day rats but rapidly decreased with time; cardiac levels of DXR-ol remained low. Hearts from DXR 7-week rats contained appreciable amounts of DXR and DXR-ol, while very low levels of DXR-ol were found in DXR-ol 7-week animals. The data correlated well with the ECG alterations recorded during the study, which were more severe in DXR- than in DXR-ol-treated rats. These results indicate that the lower tissue uptake of exogenously administered DXR-ol might explain its lower toxic cardiac potential compared with DXR.

[Indexed for MEDLINE]

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