Calcineurin inhibitors enhance low-density lipoprotein oxidation in transplant patients

Kidney Int Suppl. 1999 Jul:71:S137-40. doi: 10.1046/j.1523-1755.1999.07134.x.

Abstract

Background: Our objective was to assess the pro-oxidant status of neoral and tacrolimus in renal transplant patients and monitor the protection provided 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 from renal transplant patients receiving neoral, tacrolimus and tacrolimus with vitamin C and vitamin E. Oxidation was initiated by the addition of CuCl2 at 37 degrees C and monitored at 234 nm over 480 minutes and oxidation lag time was computed. Total antioxidant capacity of serum was measured using the enhanced chemiluminescent method.

Results: LDL from tacrolimus-treated patients had significantly lower oxidation lag time and serum antioxidant activity in comparison with neoral-treated patients, and this was particularly significant during the first four months 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-oxidant activity and they increase the susceptibility of LDL to oxidation. Neoral formulation is fortified with DL-alpha tocopherol and therefore provides protection against oxidation. The present study clearly demonstrates the benefit of giving vitamin C and E supplements to patients taking tacrolimus and this seems to be particularly important during the early period after transplantation.

MeSH terms

  • Adult
  • Ascorbic Acid / therapeutic use
  • Calcineurin Inhibitors*
  • Cholesterol / blood
  • Cyclosporine / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation*
  • Lipoproteins, LDL / blood
  • Lipoproteins, LDL / drug effects*
  • Lipoproteins, LDL / metabolism
  • Male
  • Middle Aged
  • Oxidation-Reduction
  • Tacrolimus / therapeutic use
  • Time Factors
  • Triglycerides / blood
  • Urea / blood
  • Vitamin E / therapeutic use

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Lipoproteins, LDL
  • Triglycerides
  • oxidized low density lipoprotein
  • Vitamin E
  • Cyclosporine
  • Urea
  • Cholesterol
  • Ascorbic Acid
  • Tacrolimus