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Hepatic Cholesterol Synthesis in Man: Effect of Diazepam and Other Drugs †
Author(s) -
Orlandi F.,
Bamonti F.,
Dini M.,
Koch M.,
Jezequel A.M.
Publication year - 1975
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1975.tb02279.x
Subject(s) - diazepam , endoplasmic reticulum , phenobarbital , cholesterol , chlorpromazine , microsome , stimulation , medicine , endocrinology , imipramine , pharmacology , drug , chemistry , digitonin , biochemistry , pathology , in vitro , enzyme , alternative medicine
. The hepatic synthesis of cholesterol‐measured as incorporation of 14 C‐acetate into digitonin‐precipitable sterols‐has been evaluated in needle biopsy material of normal untreated patients and patients under short‐term treatment with Diazepam, Phenobarbital, Chlorpromazine or Diphenylhydantoin. A significant increase of cholesterol synthesis was observed in the first two groups with much higher levels of incorporation in the Diazepam‐treated patients. Moreover in this group the levels were still elevated from 4 to 7 days after drug withdrawal. Ultrastructural and morphometric studies performed on the same biopsy material showed a significant increase of smooth endoplasmic reticulum in hepatocytes of Diazepam‐treated patients; in addition, there seemed to be a positive correlation between the increased cholesterol synthesis and the formation of areas of non vesicular, type 2, smooth endoplasmic reticulum. These findings suggest an early stimulation of the liver cell microsomal system by Diazepam in man; they also point to side effects of some drugs, which are not predictable from studies in Wistar rats.