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 cyclospor ine, methylprednisolone, and the combination of both (CyP) on plasma l ipids and lipoproteins levels. Three groups received a low doses of cy closporine, methylprednisolone, and CyP (cyclosporine, 15 mg/kg/day; m ethylprednisolone, 1 mg/kg/day; and CyP, 15 plus 1 mg/kg/day of cyclos porine 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 methylpre dnisolone, respectively). The administration of cyclosporine produced an increase in plasma levels of triglycerides, very low density lipopr otein (VLDL) triglycerides, low-density lipoprotein (LDL) cholesterol and in total cholesterol/HDL cholesterol and LDL cholesterol/high-dens ity lipoprotein (HDL) cholesterol ratios. In addition, cyclosporine de creased plasma HDL cholesterol and HDL(2) cholesterol levels. The admi nistration of methylprednisolone produced an increase in triglycerides and VLDL triglycerides and a decrease in HDL cholesterol and HDL(2) c holesterol levels. Total cholesterol/HDL cholesterol and LDL cholester ol/HDL cholesterol ratios did not change after administration of methy lprednisolone. The association of both drugs resulted in a greater inc rease in triglycerides and VLDL triglycerides than the separated admin istration of either cyclosporine or methylprednisolone alone. In rats receiving cyclosporine the increase in triglycerides and VLDL triglyce rides may be due to a significant decrease in plasma lipoprotein lipas e activity. By contrast, plasma lipoprotein lipase activity did not ch ange in methylprednisolone-treated rats. These results suggest that bo th 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 c holesterol, 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 marke d increase in triglycerides. Cyclosporine is responsible for an increa se in LDL cholesterol.