Plasma cholesterol-lowering activity of dietary dihydrocholesterol in hypercholesterolemia hamsters

Atherosclerosis. 2015 Sep;242(1):77-86. doi: 10.1016/j.atherosclerosis.2015.06.046. Epub 2015 Jun 27.

Abstract

Objective: Cholesterol analogs have been used to treat hypercholesterolemia. The present study was to examine the effect of dihydrocholesterol (DC) on plasma total cholesterol (TC) compared with that of β-sitosterol (SI) in hamsters fed a high cholesterol diet.

Methods and results: Forty-five male hamsters were randomly divided into 6 groups, fed either a non-cholesterol diet (NCD) or one of five high-cholesterol diets without addition of DC and SI (HCD) or with addition of 0.2% DC (DA), 0.3% DC (DB), 0.2% SI (SA), and 0.3% SI (SB), respectively, for 6 weeks. Results showed that DC added into diet at a dose of 0.2% could reduce plasma TC by 21%, comparable to that of SI (19%). At a higher dose of 0.3%, DC reduced plasma TC by 15%, less effective than SI (32%). Both DC and SI could increase the excretion of fecal sterols, however, DC was more effective in increasing the excretion of neutral sterols but it was less effective in increasing the excretion of acidic sterols compared with SI. Results on the incorporation of sterols in micellar solutions clearly demonstrated both DC and SI could displace the cholesterol from micelles with the former being more effective than the latter.

Conclusion: DC was equally effective in reducing plasma cholesterol as SI at a low dose. Plasma TC-lowering activity of DC was mediated by inhibiting the cholesterol absorption and increasing the fecal sterol excretion.

Keywords: 5α-cholestanol; Cholesterol; Sterol; β-sitosterol.

Publication types

  • Comparative Study

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / pathology
  • Animal Feed / analysis
  • Animals
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / therapeutic use*
  • Aortic Diseases / etiology
  • Aortic Diseases / pathology
  • Aortic Diseases / prevention & control
  • Atherosclerosis / etiology
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control
  • Bile Acids and Salts / analysis
  • Cholestanol / administration & dosage
  • Cholestanol / therapeutic use*
  • Cholesterol / blood*
  • Cholesterol, Dietary / administration & dosage
  • Cholesterol, Dietary / pharmacokinetics
  • Cricetinae
  • Drug Evaluation, Preclinical
  • Feces / chemistry
  • Gene Expression Profiling
  • Hyperlipoproteinemia Type II / blood
  • Hyperlipoproteinemia Type II / complications
  • Hyperlipoproteinemia Type II / diet therapy*
  • Intestinal Absorption / drug effects*
  • Lipids / blood
  • Lipoproteins / blood
  • Liver / chemistry
  • Liver / pathology
  • Male
  • Mesocricetus
  • Metabolic Networks and Pathways / genetics
  • Micelles
  • Molecular Structure
  • Organ Size / drug effects
  • Plaque, Atherosclerotic / pathology
  • RNA, Messenger / biosynthesis
  • Random Allocation
  • Sitosterols / administration & dosage
  • Sitosterols / therapeutic use
  • Sterols / analysis
  • Viscera / drug effects
  • Viscera / pathology

Substances

  • Anticholesteremic Agents
  • Bile Acids and Salts
  • Cholesterol, Dietary
  • Lipids
  • Lipoproteins
  • Micelles
  • RNA, Messenger
  • Sitosterols
  • Sterols
  • gamma-sitosterol
  • Cholestanol
  • Cholesterol