Calcineurin inhibitors enhance low-density lipoprotein oxidation in transplant patients

Abstract

Calcineurin inhibitors enhance low-density lipoprotein oxida-complexes with their respective immunophilins and tion in transplant patients.these complexes then inhibit a key enzyme serine/threo-Background. Our objective was to assess the pro-oxidant nine phosphatase, calcineurin, which is involved in the status of neoral and tacrolimus in renal transplant patients and dephosphorylation of the transcription factor NFA-T. monitor the protection provided by vitamin C and vitamin E in normalizing low density lipoprotein (LDL) oxidation lag Calcineurin-mediated dephosphorylation of NFA-T is a time of tacrolimus-treated patients. pivotal step in the transcription and translation of the Methods. Plasma LDL was isolated by density gradient ul-IL-2 gene. The susceptibility of low density lipoprotein tracentrifugation from renal transplant patients receiving neo-(LDL) to oxidation is increased by cyclosporine (CsA) ral, tacrolimus and tacrolimus with vitamin C and vitamin E.[2, 3]. Oxidized LDL (Ox-LDL) may be of critical impor-Oxidation was initiated by the addition of CuCl 2 at 37ЊC and monitored at 234 nm over 480 minutes and oxidation lag time tance in triggering a cascade of cellular processes that was computed. Total antioxidant capacity of serum was mealeads to the formation of fatty streak and eventually sured using the enhanced chemiluminescent method. atherosclerotic lesions in the artery wall [4, 5]. The sus-Results. LDL from tacrolimus-treated patients had signifi-

Assessment of Oxidative Stress in the Early Posttransplant Period: Comparison of Cyclosporine A and Tacrolimus-Based Regimens

“…Several mechanisms may be involved in the oxidant effects of these drugs. Both drugs have been reported to increase the oxidability of LDL particles [7, 8, 29]. In animal models, the metabolisms of calcineurin inhibitors are accompanied by increased free ROS, with a concomitant increase in levels of MDA, an end product of lipid peroxidation [30, 31].…”

“…However, the acute and chronic nephrotoxicities of both drugs limit their beneficial effects [5, 6]. Both drugs are reported to enhance oxidative stress and augment atherosclerosis by increasing the oxidizability of low-density lipoprotein (LDL) particles [7, 8]. Yet the data are controversial as there are inconsistent reports indicating unaltered [9] or improved oxidative stress following kidney transplantation [10, 11].…”

“…Some reports claim that different calcineurin inhibitors have different effects on oxidative stress. There may be several reasons of these distinctions as the exact mechanism is not clear [8, 12]. …”

Efeito renoprotetor dos flavonoides do vinho na nefrotoxicidade do imunossupressor Tacrolimus

“…The concomitant administration of FK506 and Vitis vinifera L promoted a significant reduction in the levels of urinary peroxides and improved renal function, observed by the increase of creatinine clearance. Another study showed the pro-oxidant action of calcineurin inhibitors through lipid peroxidation and confirmed the renoprotective effects of the use of vitamins A and C, both antioxidants (24) . The renoprotective effects afforded by Vitis vinifera L may be related to scavenging free radicals, inhibition of lipid peroxidation, or even its action in both pathways.…”

Stabilization of Oxidative Stress 1 Year after Kidney Transplantation: Effect of Calcineurin Immunosuppressives

“…26 Even though the prooxidant activities of Tac and CyA have been intensively studied, a large number of contradictory results have been published. Some authors consider CyA to be a more potent prooxidant than Tac, 27 but other studies have not confirmed these findings. 7 Our results showed that there were no significant differences between effects of CyA and Tac on OS-related parameters after transplantation.…”