title: Cyclosporin A does not increase the oxidative susceptibility of low density lipoprotein in vitro.
abstract: Accelerated atherosclerosis is the leading cause of morbidity in renal transplant recipients. The pathogenic mechanisms responsible for the progression of atherosclerosis in renal transplant recipients have not been elucidated. Cyclosporin A (CsA) is an immunosuppressive agent used post-transplant and may contribute to increased oxidative susceptibility of low density lipoprotein (LDL). There is a paucity of data testing the effect of CsA on LDL oxidation. Hence, the aim of this study was to test the effect of in vitro enrichment of LDL with CsA on LDL oxidation. LDL oxidation in presence of different concentrations of CsA was tested using metal-dependent (copper), metal-independent (AAPH) and cell-mediated (macrophages) oxidation systems. In all 3 systems, CsA had no significant effect on LDL oxidation. Also, pre-incubation of LDL with CsA did not affect LDL oxidation and LDL alpha tocopherol levels. Thus, the results of our studies with CsA indicate that it is not a direct pro-oxidant.
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235-9073, USA.
authors.forename: S
authors.initials: S
authors.lastname: Devaraj
authors.forename: D J
authors.initials: DJ
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Vazquez
authors.forename: I
authors.initials: I
authors.lastname: Jialal
mesh_terms: D000578:Amidines / Q000494:pharmacology; D002478:Cells, Cultured; D003300:Copper / Q000494:pharmacology; D016572:Cyclosporine / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology*; D009000:Monocytes / Q000502:physiology; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
chemical_list: D000578:Amidines; D007166:Immunosuppressive Agents; D008077:Lipoproteins, LDL; D016877:Oxidants; D017392:Thiobarbituric Acid Reactive Substances; C099252:oxidized low density lipoprotein; C046728:2,2'-azobis(2-amidinopropane); D003300:Copper; D016572:Cyclosporine