The combined effects of novel tocotrienols and lovastatin on lipid metabolism in chickens.
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.
Qureshi
A A
AA
Advanced Medical Research, 8251 Raymond Road, Madison, WI 53719, USA.
Peterson
D M
DM
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002645:Chickens; D002784:Cholesterol / Q000097:blood; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D004032:Diet; D004357:Drug Synergism; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000201:enzymology; D008148:Lovastatin / Q000494:pharmacology*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D008077:Lipoproteins, LDL; D014810:Vitamin E; D002784:Cholesterol; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase