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ARS Home » Midwest Area » Madison, Wisconsin » Cereal Crops Research » Research » Publications at this Location » Publication #112772
Title: THE COMBINED EFFECTS OF NOVEL TOCOTRIENOLS AND LOVASTATIN ON LIPID METABOLISM IN CHICKENS

Author
item QURESHI, ASAF - ADVANCED MEDICAL RESEARCH
item Peterson, David

Submitted to: Atherosclerosis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/17/2000
Publication Date: N/A
Citation: N/A

Interpretive Summary: High cholesterol is a risk factor for heart disease. For moderately high cholesterol, treatment by diet modification may be attempted, but for more severe cases, drugs may be prescribed. One such drug, lovastatin, is an inhibitor of an enzyme involved in cholesterol synthesis. Although this drug is effective, there are adverse side effects. Substances found in rice bran oil called tocotrienols also inhibit the same enzyme, but by a different mechanism. We did experiments with chickens, a model animal, to determine if combining lovastatin with tocotrienols might lower cholesterol in an additive or synergistic way. We found out that the combination did lower cholesterol more, and had a greater effect on the enzyme activity, than lovastatin alone. If a similar result is found in human studies, the impact is that cholesterol might be lowered with a reduced dosage of lovastatin, resulting in fewer side effects.

Technical Abstract: Both lovastatin (a fungal product) and a tocotrienol rich fraction (TRF, a mixture of tocols isolated from stabilized and heated rice bran containing desmethyl [d-P21-T3] and didesmethyl {d-P25-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 or d-P25-T3 in combination with 50 ppm lovastatin for 4 weeks. Combinations of d-P25-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 plus 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 (19%). TRF plus lovastatin decreased levels of serum total cholesterol (22%), LDL cholesterol (42%), apolipoprotein B (13-38%), triglycerides (19%), thromboxane B2 (34%) and platelet factor 4 (26%), although high-density lipoprotein (HDL) cholesterol, and apolipoprotein A1 levels were unaffected. The mixture of TRF plus lovastatin showed greater effects than did the individual treatments alone, reflecting possible additive pharmacological actions. The effects, however, of the d-P25-T3/lovastatin combination were no greater than that of d-P25-T3 alone, possibly indicating that d-P25-T3 produced a maximum cholesterol lowering effect at the concentration used.