Influence of etoposide on the retention of radiolabeled low-density lipoprotein in the arterial wall

Background.-Cardiovascular toxicity of chemotherapy for testicular cancer i s a matter of discussion, since highly efficient agents can achieve cure of the disease, even in the metastasized setting. Acute ischemic events durin g the treatment period and a persistently elevated serum cholesterol therea fter are observations of particular concern in these patients, and the unde rlying basic mechanisms are unknown to date. Objective.-To evaluate etoposide, which is part of the standard treatment f or testicular cancer, as a potential cause of atherogenesis in an experimen tal model. Setting.-Aortic I-125-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 c holesterol content was determined both by Sudan III staining and quantitati vely by a biochemical assay. Results.-A reduced uptake of I-125-labeled low-density lipoprotein in the a rterial wall was observed in the etoposide-treated animals, which resulted in a size reduction of sudanophilic areas and cholesterol content. Whereas the breakdown of I-125-labeled low-density lipoprotein in the liver was not significantly enhanced the plasma decay of I-125-labeled low-density I;lip oprotein was faster and serum cholesterol was lower in the etoposide group than in controls. Conclusion.-Unexpectedly, we found an improvement of arterial wall lipid me tabolism under etoposide treatment and can thus exclude this substance as a promoter of atherogenesis in this model.