Oxysterols Increase Inflammation, Lipid Marker Levels and Reflect Accelerated Endothelial Dysfunction in Experimental Animals

Mediators Inflamm. 2018 Mar 11:2018:2784701. doi: 10.1155/2018/2784701. eCollection 2018.

Abstract

Objective: Oxidized cholesterol derivatives are thought to exert atherogenic effect thus adversely affecting vascular endothelium. The aim of the study was to assess the effect of 5α,6α-epoxycholesterol on experimentally induced hypercholesterolemia in rabbits, and the levels of homocysteine (HCY), asymmetric dimethylarginine (ADMA), paraoxonase-1 (PON-1), and inflammatory parameters (IL-6, TNF-α, CRP).

Material and methods: The rabbits were divided into 3 groups, 8 animals each, and fed with basic fodder (C), basic fodder plus cholesterol (Ch) or basic fodder plus 5α,6α-epoxycholesterol, and unoxidized cholesterol (ECh). Serum concentrations of studied parameters were determined at 45-day intervals. The study was continued for six months.

Results: We demonstrated that adding 5α,6α-epoxycholesterol to basic fodder significantly affected lipid status of the experimental animals, increasing total cholesterol and LDL cholesterol levels, as well as HCY and ADMA levels, whilst leaving the PON-1 activity unaffected. Additionally, the ECh group presented with significantly higher concentrations of inflammatory biomarkers (IL-6, TNF-α, and CRP). In the Ch group, lower yet significant (as compared to the C group) changes of levels of studied parameters were observed.

Conclusion: Exposure of animals with experimentally induced hypercholesterolemia to 5α,6α-epoxycholesterol increases dyslipidaemia, endothelial dysfunction, and inflammatory response.

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Aryldialkylphosphatase / blood
  • C-Reactive Protein / metabolism
  • Cholesterol / blood
  • Cholesterol / pharmacology
  • Dyslipidemias / blood
  • Homocysteine / metabolism
  • Hypercholesterolemia / blood*
  • Hypercholesterolemia / chemically induced
  • Inflammation / blood*
  • Inflammation / chemically induced
  • Interleukin-6 / blood
  • Lipids / blood
  • Male
  • Oxysterols / adverse effects*
  • Rabbits
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Interleukin-6
  • Lipids
  • Oxysterols
  • Tumor Necrosis Factor-alpha
  • Homocysteine
  • N,N-dimethylarginine
  • C-Reactive Protein
  • Arginine
  • Cholesterol
  • Aryldialkylphosphatase