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.
Varghese
Z
Z
Renal Research Laboratory, Royal Free and UCL School of Medicine, London, England, United Kingdom. zac@rfhsm.ac.uk
Fernando
R L
RL
Turakhia
G
G
Psimenou
E
E
Fernando
O N
ON
Sweny
P
P
Powis
S H
SH
Moorhead
J F
JF
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