The combined effects of novel tocotrienols and lovastatin on lipid metabolism in chickens

Atherosclerosis. 2001 May;156(1):39-47. doi: 10.1016/s0021-9150(00)00612-2.

Abstract

Both lovastatin (a fungal product) and a tocotrienol rich fraction (TRF(25), a mixture of tocols isolated from stabilized and heated rice bran containing desmethyl [d-P(21)-T3] and didesmethyl [d-P(25)-T3] tocotrienols) are potent hypocholesterolemic agents, although they suppress cholesterol biosynthesis by different mechanisms. To determine additive and/or synergistic effects of both agents, chickens were fed diets supplemented with 50 ppm TRF(25) or d-P(25)-T3 in combination with 50 ppm lovastatin for 4 weeks. Combinations of d-P(25)-T3 with lovastatin were found most effective in reducing serum total cholesterol and low-density lipoprotein (LDL) cholesterol compared to the control diet or individual supplements. The mixture of TRF(25)+lovastatin inhibited the activity of beta-hydroxy-beta-methylglutaryl coenzymeA reductase (21%) compared to lovastatin alone, which did not change its activity. Cholesterol 7alpha-hydroxylase activity was increased by lovastatin (11%) and by lovastatin plus TRF(25) (19%). TRF(25)+lovastatin decreased levels of serum total cholesterol (22%), LDL cholesterol (42%), apolipoprotein B (13-38%), triglycerides (19%), thromboxane B(2) (34%) and platelet factor 4 (26%), although high-density lipoprotein (HDL) cholesterol, and apolipoprotein A1 levels were unaffected. The mixture of TRF(25)+lovastatin showed greater effects than did the individual treatments alone, reflecting possible additive pharmacological actions. The effects, however, of the d-P(25)-T3/lovastatin combination were no greater than that of d-P(25)-T3 alone, possibly indicating that d-P(25)-T3 produced a maximum cholesterol lowering effect at the concentration used.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticholesteremic Agents / pharmacology*
  • Chickens
  • Cholesterol / blood
  • Cholesterol 7-alpha-Hydroxylase / metabolism
  • Diet
  • Drug Synergism
  • Female
  • Hydroxymethylglutaryl CoA Reductases / metabolism
  • Lipid Metabolism*
  • Lipoproteins, LDL / blood
  • Liver / enzymology
  • Lovastatin / pharmacology*
  • Vitamin E / analogs & derivatives*
  • Vitamin E / pharmacology*

Substances

  • Anticholesteremic Agents
  • Lipoproteins, LDL
  • Vitamin E
  • Cholesterol
  • Lovastatin
  • Hydroxymethylglutaryl CoA Reductases
  • Cholesterol 7-alpha-Hydroxylase