Dietary phytosterols reduce cyclosporine-induced hypercholesterolemia in apolipoprotein E-knockout mice.
BACKGROUND
Cyclosporine-induced hypercholesterolemia is a major concern after solid organ transplantation. Reducing this side effect of cyclosporine by dietary agents may be safe, cost-effective, and attractive to both patients and health professionals.


METHODS
In this study, the interactions between dietary phytosterols (2% w/w) and cyclosporine (0.02% w/w) in regard to blood cyclosporine concentrations, lipoprotein profile, and histological and morphometrical features of atherosclerotic lesions were studied over 14 weeks in apolipoprotein E-knockout mice.


RESULTS
Cyclosporine alone increased plasma non-HDL cholesterol, and triglyceride concentrations and reduced HDL-cholesterol levels as compared to controls. However, these changes were not associated with further increases in atherogenesis as compared to controls. Unlike cyclosporine, phytosterols reduced non-HDL cholesterol and atherosclerosis, and increased HDL-cholesterol concentrations, as compared to the control group. The addition of dietary phytosterols to cyclosporine reduced the extent of cyclosporine-induced hypercholesterolemia, but not cyclosporine-induced hypertriglyceridemia. The extent of atherosclerosis in the combination therapy group was significantly lower than that in the control group or cyclosporine-treated group. Blood cyclosporine concentrations were comparable between the two groups of cyclosporine-treated and the combination therapy groups at the end of the study.


CONCLUSIONS
This study suggests that simultaneous consumption of dietary phytosterols and cyclosporine may attenuate posttransplant hypercholesterolemia associated with the immunosuppressive cyclosporine. Additional studies are required to understand the mechanisms by which dietary phytosterols reduce cyclosporine-induced hypercholesterolemia.
Moghadasian
Mohammed H
MH
Department of Human Nutritional Sciences, University of Manitoba and the National Centre for Agri-food Research in Medicine, St. Boniface Hospital Research Centre, Winnipeg, Manitoba, Canada. mmoghadasian@sbrc.ca
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D001835:Body Weight; D016572:Cyclosporine / Q000009:adverse effects* / Q000097:blood; D004032:Diet; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010840:Phytosterols / Q000008:administration & dosage*; D019737:Transplants / Q000009:adverse effects
D001057:Apolipoproteins E; D007166:Immunosuppressive Agents; D008055:Lipids; D010840:Phytosterols; D016572:Cyclosporine