Calcineurin inhibitors enhance low-density lipoprotein oxidation in transplant patients

Background. Our objective was to assess the pro-oxidant status of neoral an d tacrolimus in renal transplant patients and monitor the protection provid ed by vitamin C and vitamin E in normalizing low density lipoprotein (LDL) oxidation lag time of tacrolimus-treated patients. Methods. Plasma LDL was isolated by density gradient ultracentrifugation fr om renal transplant patients receiving neoral, tacrolimus and tacrolimus wi th vitamin C and vitamin E. Oxidation was initiated by the addition of CuCl 2 at 37 degrees C and monitored at 234 nm over 480 minutes and oxidation la g time was computed. Total antioxidant capacity of serum was measured using the enhanced chemiluminescent method. Results. LDL from tacrolimus-treated patients had significantly lower oxida tion lag time and serum antioxidant activity in comparison with neoral-trea ted patients, and this was particularly significant during the first four m onths after transplantation. Vitamin C and E supplementation in tacrolimus treated patients provided protection against oxidation and normalized their oxidation lag time. Conclusion. Calcineurin-inhibiting drugs, CsA and tacrolimus, have pro-oxid ant activity and they increase the susceptibility of LDL to oxidation. Neor al formulation is fortified with DL-alpha tocopherol and therefore provides protection against oxidation. The present study clearly demonstrates the b enefit of giving vitamin C and E supplements to patients taking tacrolimus and this seems to be particularly important during the early period after t ransplantation.