Detection of acrolein-lysine adducts in plasma low-density lipoprotein and in aorta of cyclophosphamide-administered rats.

Cyclophosphamide (CY) is an alkylating agent used for the treatment of various types of cancer and is also used as a potent immunosuppressant. Acrolein, a metabolite of CY is cytotoxic and has the ability to covalently bind with proteins in vitro to form acrolein-protein adducts. These protein adducts are considered to be putative markers of oxidative stress and cause damage to protein in aging, atherosclerosis and diabetes. We have, for the first time, detected acrolein-lysine adducts in plasma low-density lipoprotein (LDL) and in the aorta of CY-treated animals by agarose gel electrophoresis, immunoblot and immunohistochemical methods. The extent of lipid peroxidation caused by the metabolite acrolein in plasma LDL was also measured quantitatively by using high-performance liquid chromatography. These results confirm the role of acrolein-lysine adducts in the development of atherosclerosis or atherogenesis.