Influence of etoposide on the retention of radiolabeled low-density lipoprotein in the arterial wall.
BACKGROUND
Cardiovascular toxicity of chemotherapy for testicular cancer is a matter of discussion, since highly efficient agents can achieve cure of the disease, even in the metastasized setting. Acute ischemic events during the treatment period and a persistently elevated serum cholesterol thereafter are observations of particular concern in these patients, and the underlying basic mechanisms are unknown to date.


OBJECTIVE
To evaluate etoposide, which is part of the standard treatment for testicular cancer, as a potential cause of atherogenesis in an experimental model.


METHODS
Aortic 125I-labeled low-density lipoprotein retention was studied in 72 cholesterol-fed rabbits under etoposide treatment and was quantified according to the morphologically assessed type of surface lining. Aortic cholesterol content was determined both by Sudan III staining and quantitatively by a biochemical assay.


RESULTS
A reduced uptake of 125I-labeled low-density lipoprotein in the arterial wall was observed in the etoposide-treated animals, which resulted in a size reduction of sudanophilic areas and cholesterol content. Whereas the breakdown of 125I-labeled low-density lipoprotein in the liver was not significantly enhanced, the plasma decay of 125I-labeled low-density lipoprotein was faster and serum cholesterol was lower in the etoposide group than in controls.


CONCLUSIONS
Unexpectedly, we found an improvement of arterial wall lipid metabolism under etoposide treatment and can thus exclude this substance as a promoter of atherogenesis in this model.
Krainer
M
M
Department of Internal Medicine, Division of Oncology, University Hospital, Vienna, Austria.
Rodrigues
M
M
ZielinskiMD
C
C
Sinzinger
H
H
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000139:chemically induced / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D008078:Cholesterol, LDL / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology*; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011817:Rabbits; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D002791:Cholesterol, Dietary; D008078:Cholesterol, LDL; D007457:Iodine Radioisotopes; D005047:Etoposide; D002784:Cholesterol; D011464:Epoprostenol