Calcineurin inhibitors enhance low-density lipoprotein oxidation in transplant patients.
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.


CONCLUSIONS
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.
Renal Research Laboratory, Royal Free and UCL School of Medicine, London, England, United Kingdom. zac@rfhsm.ac.uk
Z
Z
Varghese
R L
RL
Fernando
G
G
Turakhia
E
E
Psimenou
O N
ON
Fernando
P
P
Sweny
S H
SH
Powis
J F
JF
Moorhead
D000328:Adult; D001205:Ascorbic Acid / Q000627:therapeutic use; D065095:Calcineurin Inhibitors; D002784:Cholesterol / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D016559:Tacrolimus / Q000627:therapeutic use; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D014508:Urea / Q000097:blood; D014810:Vitamin E / Q000627:therapeutic use
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D008077:Lipoproteins, LDL; D014280:Triglycerides; C099252:oxidized low density lipoprotein; D014810:Vitamin E; D016572:Cyclosporine; D014508:Urea; D002784:Cholesterol; D001205:Ascorbic Acid; D016559:Tacrolimus