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

Journal Article · Mon Sep 17 00:00:00 EDT 1979 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(79)90591-5· OSTI ID:7055897

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
• OSTI ID: 7055897
• Journal Information: Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 25:12; ISSN LIFSA
• Country of Publication: United States
• Language: English

Related Subjects

550300 -- Cytology
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL TISSUES
ANIMALS
ANTIBIOTICS
BIOLOGICAL EFFECTS
BODY
CALCIUM IONS
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
CHARGED PARTICLES
COMPARATIVE EVALUATIONS
CYTOPLASM
DIGESTIVE SYSTEM
DOXORUBICIN
DRUGS
ENZYME ACTIVITY
GLANDS
HEART
IN VITRO
IN VIVO
IONS
KIDNEYS
LIVER
MAMMALS
METABOLISM
METABOLITES
MITOCHONDRIA
MORPHOLOGICAL CHANGES
ORGANOIDS
ORGANS
RABBITS
SENSITIVITY
TISSUES
UPTAKE
VERTEBRATES