Effects of doxorubicin and its aglycone metabolite on calcium sequestration by rabbit heart, liver, and kidney mitochondria

Journal Article · Mon Jan 01 04:00:00 EST 1979 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(79)90591-5· OSTI ID:7098589

Revis, N W; Marusic, N

Previous investigators have shown that following doxorubicin treatment heart mitochondria appear swollen and contain intramitochondrial dense inclusion bodies identified as calcium phosphate. In vitro studies have shown that similar morphological changes occur in mitochondria previously loaded with excess calcium. The present studies were performed to determine the effects of doxorubicin and its aglycone metabolite on /sup 45/Ca/sup 2 +/ uptake by mitochondria isolated from the heart, liver, and kidney of the rabbit. Doxorubicin (100 ..mu..M) significantly inhibited the initial rate of /sup 45/Ca/sup 2 +/ accumulated by mitochondria isolated from the three tissues. In contrast, the aglycone metabolite (100 ..mu..M) induced the reverse effect. In preloaded mitochondria the aglycone stimulated the release of calcium while doxorubicin was without effect. Mitochondria from the heart were significantly more sensitive to the effects of these anthracyclines than were mitochondria from the other two tissues. If these in vitro effects also occur in vivo, then the aglycone metabolite would be a more likely candidate in explaining the morphological changes in heart mitochondria previously described.

• Research Organization: Oak Ridge National Lab., TN
• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 7098589
• Journal Information: Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 25:12; ISSN LIFSA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ALKALINE EARTH ISOTOPES
ANIMALS
ANTIBIOTICS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL ACCUMULATION
BIOLOGICAL EFFECTS
BODY
CALCIUM 45
CALCIUM ISOTOPES
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
CHEMOTHERAPY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DOXORUBICIN
DRUGS
EVEN-ODD NUCLEI
GLANDS
HEART
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KIDNEYS
LIVER
MAMMALS
METABOLISM
METABOLITES
MITOCHONDRIA
MORPHOLOGICAL CHANGES
NUCLEI
ORGANOIDS
ORGANS
RABBITS
RADIOISOTOPES
SIDE EFFECTS
THERAPY
TRACER TECHNIQUES
VERTEBRATES