THE EFFECT OF CYCLOSPORINE AND METHYLPREDNISOLONE ON PLASMA-LIPOPROTEIN LEVELS IN RATS

The aim of this study was to evaluate in rats the effects of cyclosporine, methylprednisolone, and the combination of both (CyP) on plasma lipids and lipoproteins levels. Three groups received a low doses of cyclosporine, methylprednisolone, and CyP (cyclosporine, 15 mg/kg/day; methylprednisolone, 1 mg/kg/day; and CyP, 15 plus 1 mg/kg/day of cyclosporine and methylprednisolone, respectively). Three additional groups received high doses (cyclosporine, 30 mg/kg/day; methylprednisolone, 2 mg/kg/day; and CyP, 30 plus 2 mg/kg/day of cyclosporine and methylprednisolone, respectively). The administration of cyclosporine produced an increase in plasma levels of triglycerides, very low density lipoprotein (VLDL) triglycerides, low-density lipoprotein (LDL) cholesterol and in total cholesterol/HDL cholesterol and LDL cholesterol/high-density lipoprotein (HDL) cholesterol ratios. In addition, cyclosporine decreased plasma HDL cholesterol and HDL(2) cholesterol levels. The administration of methylprednisolone produced an increase in triglycerides and VLDL triglycerides and a decrease in HDL cholesterol and HDL(2) cholesterol levels. Total cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol ratios did not change after administration of methylprednisolone. The association of both drugs resulted in a greater increase in triglycerides and VLDL triglycerides than the separated administration of either cyclosporine or methylprednisolone alone. In rats receiving cyclosporine the increase in triglycerides and VLDL triglycerides may be due to a significant decrease in plasma lipoprotein lipase activity. By contrast, plasma lipoprotein lipase activity did not change in methylprednisolone-treated rats. These results suggest that both drugs have an additive effect in increasing triglycerides and VLDL triglycerides levels. Furthermore, the combination of cyclosporine and methylprednisolone produced an increase in LDL cholesterol and VLDL cholesterol, and a decrease in HDL cholesterol and HDL(2) cholesterol. In summary, cyclosporine and methylprednisolone have separate effects on plasma lipid levels; the combination of both drugs produces a marked increase in triglycerides. Cyclosporine is responsible for an increase in LDL cholesterol.