Effect of Ciclosporin on Serum Lipids and Modification with LSL 90202, a Lysine Salt of Eicosapentaenoic Acid

Abstract

Ciclosporin (CS-A) has recently been considered a separate risk factor for the development of hyperlipidemia in transplant patients. In the present work, the effect of chronic CS-A administration on serum lipids and its modification using dietary supplementation with LSL 90202, a lysine salt of eicosapentaenoic acid, was studied. Thirty-one male Wistar rats were divided into four groups, receiving (1) 20 mg/kg CS-A in olive oil (CS-A group; n = 8); (2) isovolumetric olive oil (olive oil group; n = 8); (3) 20 mg/kg CS-A in olive oil plus 20 mg/kg LSL 90202 (CS-A + LSL 20 group;) and (4) 20 mg/kg CS-A in olive oil plus 40 mg/kg LSL 90202 (CS-A + LSL 40 group; n = 8). Both, CS-A and LSL 90202 were given by daily gavage. On day 28, CS-A whole-blood levels and serum levels of total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol fractions (HDL, HDL-2, HDL-3, non-HDL), and malondialdehyde were measured. On day 28, the rats given CS-A showed significantly higher cholesterol, triglyceride, and non-HDL cholesterol serum levels than rats given olive oil. Rats given CS-A and LSL 90202 (20 mg/kg) showed significantly lower triglyceride serum levels than rats given CS-A only. Rats given CS-A and LSL 90202 (40 mg/kg) showed significantly lower triglyceride, total cholesterol, and non-HDL cholesterol serum levels than rats given CS-A only. There were no differences in HDL, HDL-2, and HDL-3 cholesterol serum levels between the groups. The CS-A whole-blood levels were not different between groups of animals given CS-A. The rats given CS-A and CS-A plus LSL 90202 (20 mg/kg) showed similar malondialdehyde serum levels which were higher than in rats given olive oil. The rats given CS-A plus LSL 90202 (40 mg/kg) showed significantly higher malondialdehyde serum levels than the animals given CS-A only. In summary, our results show that CS-A can produce hyperlipidemia and that dietary supplementation with LSL 90202 may be considered a therapeutic approach for the correction of hyperlipidemia associated with CS-A.