EFFECT OF CYCLOSPORINE ON SERUM-LIPIDS AND MODIFICATION WITH LSL-90202, A LYSINE SALT OF EICOSAPENTAENOIC ACID

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 lipid s and its modification using dietary supplementation with LSL 90202, a lysine salt of eicosapentaenoic acid, was studied. Thirty-one male Wi star rats were divided into four groups, receiving (1) 20 mg/kg CS-A i n olive oil (CS-A group; n = 8); (2) isovolumetric olive oil (olive oi l group; n = 8); (3) 20 mg/kg CS-A in olive oil plus 20 mg/kg LSL 9020 2 (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 w ere given by daily gavage. On day 28, CS-A whole-blood levels and seru m levels of total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol fractions (HDL, HDL-2, HDL-3, non-HDL), and malondia ldehyde were measured. On day 28, the rats given CS-A showed significa ntly higher cholesterol, triglyceride, and non-HDL cholesterol serum l evels than rats given olive oil. Rats given CS-A and LSL 90202 (20 mg/ kg) showed significantly lower triglyceride serum levels than rats giv en CS-A only. Rats given CS-A and LSL 90202 (40 mg/kg) showed signific antly lower triglyceride, total cholesterol, and non-HDL cholesterol s erum levels than rats given CS-A only. There were no differences in HD L, HDL-2, and HDL-3 cholesterol serum levels between the groups. The C S-A whole-blood levels were not different between groups of animals gi ven CS-A. The rats given CS-A and CS-A plus LSL 90202 (20 mg/kg) showe d 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 giv en CS-A only. In summary, our results show that CS-A can produce hyper lipidemia and that dietary supplementation with LSL 90202 may be consi dered a therapeutic approach for the correction of hyperlipidemia asso ciated with CS-A.