Sequestration of /sup 45/Ca/sup 2 +/ by mitochondria from rabbit heart, liver, and kidney after doxorubicin or digoxin/doxorubicin treatment

Journal Article · Sun Dec 31 23:00:00 EST 1978 · Exp. Mol. Pathol.; (United States)

DOI:https://doi.org/10.1016/0014-4800(79)90043-1· OSTI ID:6500655

Revis, N; Marusic, N

Doxorubicin, an antibiotic of the anthracycline group, has proven effective in treating a variety of malignant disorders. However, its use has been limited due to the cardiotoxic side effects which include myocardial necrosis that is characterized by mitochondrial calcification. The present studies were conducted to determine if treatment of rabbits with doxorubicin (an anthracycline) would affect the ability of mitochondria isolated from heart, liver, and kidney to retain /sup 45/Ca/sup 2 +/. Increases in mitochondrial retention of /sup 45/Ca/sup 2 +/ by all of the tissues studied were observed, although only that from the heart showed a significant increase. The changes in /sup 45/Ca/sup 2 +/ retention and morphology (i.e., increased mitochondrial swelling and intra-mitochondrial calcium phosphate crystals) of heart mitochondria from doxorubicin-treated rabbits suggest that this anthracycline directly or indirectly affects mitochondrial flux of calcium. That liver and kidney (as compared to heart) mitochondria are relatively insensitive to the effects of doxorubicin suggests a chemical difference in the mitochondria isolated from these tissues. Digoxin/doxorubicin treatment of rabbits, however, leads to a decrease in mitochondrial retention of /sup 45/Ca/sup 2 +/, except for heart tissue, which again was significantly increased over the control. The effects of this treatment on the Na/sup +//K/sup +/ activated ATPase of the heart, and on the accumulation of doxorubicin by the heart, were not significantly different from the control, suggesting that digoxin and doxorubicin do not compete for the same binding site.

• Research Organization: Oak Ridge National Lab., TN
• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 6500655
• Journal Information: Exp. Mol. Pathol.; (United States), Journal Name: Exp. Mol. Pathol.; (United States) Vol. 31; ISSN EXMPA
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560172* -- Radiation Effects-- Nuclide Kinetics & Toxicology-- Animals-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALINE EARTH ISOTOPES
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTINEOPLASTIC DRUGS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BODY
CALCIUM 45
CALCIUM ISOTOPES
CARBOHYDRATES
CARDIAC GLYCOSIDES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DIGITALIS GLYCOSIDES
DIGOXIN
DOXORUBICIN
DRUGS
EVEN-ODD NUCLEI
GLANDS
GLYCOSIDES
HEART
INTERMEDIATE MASS NUCLEI
ISOTOPES
KIDNEYS
LIVER
MAMMALS
METABOLISM
MITOCHONDRIA
NUCLEI
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
RABBITS
RADIOISOTOPES
RADIONUCLIDE KINETICS
RESPONSE MODIFYING FACTORS
RETENTION
VERTEBRATES