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Time course of doxorubicin accumulation and dysfunction in the rat aorta
Author(s) -
Gibson Noah M.,
Hydock David S.,
Hayward Reid
Publication year - 2012
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.26.1_supplement.866.9
Subject(s) - doxorubicin , medicine , pharmacology , anthracycline , vasodilation , aorta , saline , vascular tissue , toxicity , endothelium , endothelial dysfunction , chemotherapy , biology , cancer , breast cancer , botany
Doxorubicin (DOX) is a highly effective anthracycline antibiotic used to treat a wide array of cancers. Its use is limited due to dose‐dependent acute and chronic cardiovascular toxicity. However, little is known about the mechanisms of DOX induced vascular dysfunction. The purpose of this study was to determine if DOX accumulates in vascular tissue and contributes to the onset and progression of vascular dysfunction over time. Male Sprague‐Dawley rats were randomly assigned to receive 15 mg DOX/kg of body mass or saline (SAL); DOX rats were further randomized to be sacrificed 1, 3 or 5 days post treatment. Isolated aortic rings were used to examine vascular function, and aortic DOX accumulation was quantified using high performance liquid chromatography. While DOX did in fact accumulate in vascular tissue (204±89 ng DOX/g LV) within 24 hours, there was no significant difference in accumulation over time (183±107 ng DOX/g LV at 3 days; 156±60 ng DOX/g LV at 5 days). There were significant differences between SAL and DOX groups (p<0.05) in vasocontriction, endothelium‐dependent and ‐ independent vasodilation, however there were no functional differences over time with DOX treatment. Our results show that there is early‐onset, sustained vascular dysfunction during the 5 days following DOX treatment, which is accompanied by a sustained accumulation of DOX in vascular tissue.