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. SETTING: 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. CONCLUSION: 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.