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2‐Hydroxypropyl‐β‐cyclodextrin reduces retinal cholesterol in wild‐type and Cyp27a1 −/− Cyp46a1 −/− mice with deficiency in the oxysterol production
Author(s) -
ElDarzi Nicole,
Mast Natalia,
Petrov Alexey M.,
Pikuleva Irina A.
Publication year - 2021
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.15209
Subject(s) - oxysterol , cyp27a1 , cholesterol , liver x receptor , retinal , ldl receptor , biology , biochemistry , endocrinology , chemistry , medicine , lipoprotein , nuclear receptor , gene , transcription factor
2-Hydroxypropyl-β-cyclodextrin (HPCD) is an FDA approved vehicle for drug delivery and an efficient cholesterol-lowering agent. HPCD was proposed to lower tissue cholesterol via multiple mechanisms including those mediated by oxysterols. CYP27A1 and CYP46A1 are the major oxysterol-producing enzymes in the retina that convert cholesterol to 27- and 24-hydroxycholesterol, respectively. We investigated whether HPCD treatments affected the retina of wild-type and Cyp27a1 -/- Cyp46a1 -/- mice that do not produce the major retinal oxysterols.