Cyclosporine increases the oxidizability of low-density lipoproteins in renal transplant recipients.
Blood specimens from twenty-six renal transplant recipients treated with cyclosporine (CsA) were collected at weekly intervals, two months after transplantation. Specimens were grouped according to their CsA concentrations. Group I consisted of ten specimens with CsA concentration of >400 ng/ml; group II consisted of ten specimens with CsA concentrations ranging from 120-300 ng/ml; and group III consisted of six specimens with CsA concentrations of < 100 ng/ml. In addition, specimens from five renal transplant patients who, instead of CsA, received the immunosuppressant FK506 (group IV), and from six healty individuals were included. Plasma low-density lipoproteins (LDL) were isolated and their susceptibility to oxidation was studied by continuously monitoring the formation of conjugated dienes during copper ion-mediated oxidation. Patients with higher blood concentrations of CsA (groups I and II) had significantly higher oxidizability of LDL, as indicated by the shorter time required to start the oxidation (lag phase). The oxidizability of samples with low concentration of CsA (group III) was not significantly different from that of FK506-treated patients or healthy individuals. There was a negative correlation (r = -0702, P < 0.01) between oxidizability (lag phase) and CsA concentration in LDL. No correlation between blood CsA and plasma cholesterol or triglyceride concentration was evident during a three-month period postoperatively. Similarly, no correlation between the degree of oxidizability and plasma cholesterol or triglycerides was found at the time of the experiment. These findings suggest a prooxidant effect of CsA to plasma LDL, and may indicate that CsA is an important risk factor in the accelerated atherosclerosis of renal transplant recipients.
Apanay
D C
DC
Department of Pathology, Emory University Hospital, Atlanta, Georgia 30322.
Neylan
J F
JF
Ragab
M S
MS
Sgoutas
D S
DS
D002784:Cholesterol / Q000097:blood; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use*; D005227:Fatty Acids / Q000032:analysis; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D016030:Kidney Transplantation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010084:Oxidation-Reduction; D016559:Tacrolimus / Q000627:therapeutic use; D017392:Thiobarbituric Acid Reactive Substances; D014184:Transplantation, Homologous; D014280:Triglycerides / Q000097:blood
D005227:Fatty Acids; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; D016572:Cyclosporine; D002784:Cholesterol; D016559:Tacrolimus