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• W2005215222 abstract "Orphan nuclear receptors (ONRs) have been implicated in the regulation of lipids. Several clinical studies conducted either prospectively or epidemiologically have pointed to a link between the regulation of hepatic CYP enzymes and HDL-cholesterol (HDL-C) and/or apolipoprotein A1 (apoA1). The treatment of rats with a series of imidazole inducers of CYP3A yielded correlations between in vitro CYP3A activity measured as erythromycin demethylase activity and plasma HDL-C and hepatic apoA1 mRNA. Similarly, a correlation was established between in vivo CYP3A activity, measured as ethosuximide clearance, and plasma HDL-C and hepatic apoA1 mRNA. The treatment of wild-type (WT) mice with PXR agonists elicited increases in serum HDL-C and serum apoA1 levels. On the other hand, the treatment of PXR-knockout mice (PXR-KOs) with the same PXR agonists failed to elicit increases in either serum HDL-C or serum apoA1 levels. Superposition of the structures of three imidazoles known to be active CYP3A inducers in rats with the human PXR pharmacophore demonstrated a partial fit and predicted EC50 values typical of weak-moderate hPXR inducers in humans. These imidazoles have been shown to increase apoA1 and HDL-C in rats and mice. Taken together, these data suggest that PXR plays an important role in the regulation of apoA1 and HDL-C in rodents." @default.
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• W2005215222 date "2004-09-01" @default.
• W2005215222 modified "2023-10-14" @default.
• W2005215222 title "PXR and the regulation of apoA1 and HDL-cholesterol in rodents" @default.
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• W2005215222 doi "https://doi.org/10.1016/j.phrs.2004.03.005" @default.
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