Skeletal Muscle an Active Compartment in the Sequestering and Metabolism of Doxorubicin Chemotherapy.
Doxorubicin remains one of the most widely used chemotherapeutic agents however its effect on healthy tissue, such as skeletal muscle, remains poorly understood. The purpose of the current study was to examine the accumulation of doxorubicin (DOX) and its metabolite doxorubicinol (DOXol) in skeletal...
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Format: | Article |
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Public Library of Science (PLoS)
2015-01-01
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Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4581622?pdf=render |
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author | Sergio Fabris David A MacLean |
author_facet | Sergio Fabris David A MacLean |
author_sort | Sergio Fabris |
collection | DOAJ |
description | Doxorubicin remains one of the most widely used chemotherapeutic agents however its effect on healthy tissue, such as skeletal muscle, remains poorly understood. The purpose of the current study was to examine the accumulation of doxorubicin (DOX) and its metabolite doxorubicinol (DOXol) in skeletal muscle of the rat up to 8 days after the administration of a 1.5 or 4.5 mg kg-1 i.p. dose. Subsequent to either dose, DOX and DOXol were observed in skeletal muscle throughout the length of the experiment. Interestingly an efflux of DOX was examined after 96 hours, followed by an apparent re-uptake of the drug which coincided with a spike and rapid decrease of plasma DOX concentrations. The interstitial space within the muscle did not appear to play a significant rate limiting compartment for the uptake or release of DOX or DOXol from the tissue to the circulation. Furthermore, there was no evidence that DOX preferentially accumulated in a specific muscle group with either dose. It appears that the sequestering of drug in skeletal muscle plays an acute and important role in the systemic availability and metabolism of DOX which may have a greater impact on the clinical outcome than previously considered. |
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institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-04-13T00:13:43Z |
publishDate | 2015-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
spelling | doaj.art-855e0cdc3fcb453eb126228fad21e9792022-12-22T03:11:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013907010.1371/journal.pone.0139070Skeletal Muscle an Active Compartment in the Sequestering and Metabolism of Doxorubicin Chemotherapy.Sergio FabrisDavid A MacLeanDoxorubicin remains one of the most widely used chemotherapeutic agents however its effect on healthy tissue, such as skeletal muscle, remains poorly understood. The purpose of the current study was to examine the accumulation of doxorubicin (DOX) and its metabolite doxorubicinol (DOXol) in skeletal muscle of the rat up to 8 days after the administration of a 1.5 or 4.5 mg kg-1 i.p. dose. Subsequent to either dose, DOX and DOXol were observed in skeletal muscle throughout the length of the experiment. Interestingly an efflux of DOX was examined after 96 hours, followed by an apparent re-uptake of the drug which coincided with a spike and rapid decrease of plasma DOX concentrations. The interstitial space within the muscle did not appear to play a significant rate limiting compartment for the uptake or release of DOX or DOXol from the tissue to the circulation. Furthermore, there was no evidence that DOX preferentially accumulated in a specific muscle group with either dose. It appears that the sequestering of drug in skeletal muscle plays an acute and important role in the systemic availability and metabolism of DOX which may have a greater impact on the clinical outcome than previously considered.http://europepmc.org/articles/PMC4581622?pdf=render |
spellingShingle | Sergio Fabris David A MacLean Skeletal Muscle an Active Compartment in the Sequestering and Metabolism of Doxorubicin Chemotherapy. PLoS ONE |
title | Skeletal Muscle an Active Compartment in the Sequestering and Metabolism of Doxorubicin Chemotherapy. |
title_full | Skeletal Muscle an Active Compartment in the Sequestering and Metabolism of Doxorubicin Chemotherapy. |
title_fullStr | Skeletal Muscle an Active Compartment in the Sequestering and Metabolism of Doxorubicin Chemotherapy. |
title_full_unstemmed | Skeletal Muscle an Active Compartment in the Sequestering and Metabolism of Doxorubicin Chemotherapy. |
title_short | Skeletal Muscle an Active Compartment in the Sequestering and Metabolism of Doxorubicin Chemotherapy. |
title_sort | skeletal muscle an active compartment in the sequestering and metabolism of doxorubicin chemotherapy |
url | http://europepmc.org/articles/PMC4581622?pdf=render |
work_keys_str_mv | AT sergiofabris skeletalmuscleanactivecompartmentinthesequesteringandmetabolismofdoxorubicinchemotherapy AT davidamaclean skeletalmuscleanactivecompartmentinthesequesteringandmetabolismofdoxorubicinchemotherapy |