Document Detail

Calcineurin inhibitors enhance low-density lipoprotein oxidation in transplant patients.
MedLine Citation:
PMID:  10412758     Owner:  NLM     Status:  MEDLINE    
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.
Z Varghese; R L Fernando; G Turakhia; E Psimenou; O N Fernando; P Sweny; S H Powis; J F Moorhead
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Kidney international. Supplement     Volume:  71     ISSN:  0098-6577     ISO Abbreviation:  Kidney Int. Suppl.     Publication Date:  1999 Jul 
Date Detail:
Created Date:  1999-09-15     Completed Date:  1999-09-15     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7508622     Medline TA:  Kidney Int Suppl     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  S137-40     Citation Subset:  IM    
Renal Research Laboratory, Royal Free and UCL School of Medicine, London, England, United Kingdom.
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MeSH Terms
Ascorbic Acid / therapeutic use
Calcineurin / antagonists & inhibitors*
Cholesterol / blood
Cyclosporine / therapeutic use
Drug Therapy, Combination
Immunosuppressive Agents / therapeutic use
Kidney Transplantation*
Lipoproteins, LDL / blood,  drug effects*,  metabolism
Middle Aged
Tacrolimus / therapeutic use
Time Factors
Triglycerides / blood
Urea / blood
Vitamin E / therapeutic use
Reg. No./Substance:
0/Immunosuppressive Agents; 0/Lipoproteins, LDL; 0/Triglycerides; 0/oxidized low density lipoprotein; 109581-93-3/Tacrolimus; 1406-18-4/Vitamin E; 50-81-7/Ascorbic Acid; 57-13-6/Urea; 57-88-5/Cholesterol; 59865-13-3/Cyclosporine; EC

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