TY - JOUR
T1 - Cyclosporine, Low-Density Lipoprotein, and Cholesterol
AU - de GROEN, PIET C.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1988
Y1 - 1988
N2 - Lipoproteins are known to be able to transport a variety of drugs. This report suggests that low-density lipoprotein not only functions as an important carrier of cyclosporine in plasma but also facilitates transport of cyclosporine across the cell membrane by means of the low-density lipoprotein receptor. Such a mechanism would explain (1) the similar tissue distribution of cyclosporine and the low-density lipoprotein receptor, (2) the increase in immunosuppression and toxicity with low total serum cholesterol levels, and (3) the relative absence of immunosuppression and toxicity with high levels of cyclosporine in the blood in patients with hypertriglyceridemia. In addition to receptor-mediated uptake, a disturbance of the blood-brain barrier is suggested as an explanation of the high frequency of cyclosporine-induced central nervous system toxicity after liver transplantation. Cyclosporine-induced inhibition of the mitochondrial steroid 26-hydroxylase, an enzyme involved in the formation of bile acids from cholesterol and deficient in patients with cerebrotendinous xanthomatosis, may cause or contribute to the observed central nervous system toxicity. It also may explain the similar clinical features of cyclosporine-induced central nervous system toxicity and cerebrotendinous xanthomatosis.
AB - Lipoproteins are known to be able to transport a variety of drugs. This report suggests that low-density lipoprotein not only functions as an important carrier of cyclosporine in plasma but also facilitates transport of cyclosporine across the cell membrane by means of the low-density lipoprotein receptor. Such a mechanism would explain (1) the similar tissue distribution of cyclosporine and the low-density lipoprotein receptor, (2) the increase in immunosuppression and toxicity with low total serum cholesterol levels, and (3) the relative absence of immunosuppression and toxicity with high levels of cyclosporine in the blood in patients with hypertriglyceridemia. In addition to receptor-mediated uptake, a disturbance of the blood-brain barrier is suggested as an explanation of the high frequency of cyclosporine-induced central nervous system toxicity after liver transplantation. Cyclosporine-induced inhibition of the mitochondrial steroid 26-hydroxylase, an enzyme involved in the formation of bile acids from cholesterol and deficient in patients with cerebrotendinous xanthomatosis, may cause or contribute to the observed central nervous system toxicity. It also may explain the similar clinical features of cyclosporine-induced central nervous system toxicity and cerebrotendinous xanthomatosis.
UR - http://www.scopus.com/inward/record.url?scp=0023745182&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023745182&partnerID=8YFLogxK
U2 - 10.1016/S0025-6196(12)64916-7
DO - 10.1016/S0025-6196(12)64916-7
M3 - Article
C2 - 3172850
AN - SCOPUS:0023745182
SN - 0025-6196
VL - 63
SP - 1012
EP - 1021
JO - Mayo Clinic Proceedings
JF - Mayo Clinic Proceedings
IS - 10
ER -