Short-Term Effect of Various Doses of Cyclosporin A on Plasma Lipoproteins and its Distribution in Blood: An Experimental Study

Abstract

Hyperlipidaemia commonly develops in both transplant recipients and experimental animals receiving cyclosporin A (CsA). However, the threshold of CsA induced-changes on lipoproteins and the role of parenteral vehicle (cremophor) has not been defined. Male Wistar rats were classified into five groups of six animals each and received CsA in cremophor vehicle at doses of 5, 10 or 20 mg kg-1 d-1, s.c., vehicle alone or saline for 7 d. Blood was obtained 24 h after the last dose and plasma was analysed. Plasma very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein subfractions (HDL-2, HDL-3) were isolated by sequential ultracentrifugation and their content of cholesterol, triglyceride and phospholipid was determined. Whole blood and trough plasma CsA levels were measured by monoclonal radioimmunoassay. Plasma lipids did not differ significantly among the five groups. At a dose of 20 mg kg-1 d-1 of CsA VLDL cholesterol rose significantly (P<0.05). Administration of either CsA or cremophor vehicle increased HDL-2 phospholipids (P<0.05) and decreased HDL-3 cholesterol. There was not a linear relationship between whole blood and plasma CsA levels and increasing CsA doses. Short-term treatment with low doses of CsA have little influence on lipid profile in the rat. Changes on lipoprotein composition can be attributed mainly to cremophor vehicle, conceivably due to its ethanol content.