Suppression of hepatic cholesterogenesis in the rat by lithium ion

1968 ◽  
Vol 46 (2) ◽  
pp. 135-139 ◽  
Author(s):  
R. S. Leal ◽  
M. L. M. Lyra

The effects of lithium ion on the rates of incorporation of acetate-1-14C and mevalonic-2-14C acid into cholesterol, on 14CO2 production and acetoacetate formation from carboxyl-labeled acetate, on serum and liver cholesterol levels, and on the acetate-activating system were studied in rat liver.It has been found that while the incorporation of labeled acetate into cholesterol was strongly suppressed by lithium ion, incorporation of mevalonate into cholesterol under the same conditions was virtually unchanged. It thus appears that lithium ion produces its effect prior to the formation of mevalonic acid in the pathway of cholesterol biosynthesis.Liver cholesterol levels are practically unchanged after 4 weeks' treatment with lithium chloride while serum cholesterol, under the same conditions, appears to be slightly increased in the treated animals. 14CO2 production and acetoacetate formation from carboxyl-labeled acetate, and the acetate-activating system of rat liver appear to be slightly impaired by lithium ion. The possibility of the existence of more than one block between acetate and mevalonic acid on the cholesterol biosynthetic pathway is discussed.

1968 ◽  
Vol 46 (1) ◽  
pp. 81-84 ◽  
Author(s):  
W. E. J. Phillips ◽  
M. R. Lakshmanan ◽  
R. L. Brien

Chlorophenoxyisobutyrate (CPIB) when fed in the diet at 0.2% for periods of from 3 to 25 days increased liver weight by 28% and increased total liver ubiquinones by 75%. This increase did not change succinate-neotetrazolium reductase activity. Although serum cholesterol levels were significantly reduced, no changes were observed in total liver cholesterol or vitamin A. The data suggest that this hypocholesterolemic agent, although it increases ubiquinone, does not adversely affect the above enzyme activity nor does it modify vitamin A utilization as determined from liver stores.


1959 ◽  
Vol 197 (6) ◽  
pp. 1339-1340 ◽  
Author(s):  
William T. Beher ◽  
Gizella D. Baker

The effects of dietary cholic acid on free, total and ester cholesterol levels in liver and serum, and on the relative rates of incorporation of acetate-1-C14 and mevalonic acid-2-C14 were investigated in the rat. Cholic acid caused equally significant increases in free and ester liver cholesterol. No significant changes were found in serum cholesterol levels. The incorporation rate of acetate-1-C14 into liver and serum cholesterol was inhibited by 65% when cholic acid was fed to rats, while the inhibition of mevalonic acid-2-C14 incorporation was 25%. It is suggested that cholic acid inhibits cholesterol biosynthesis between mevalonic acid and cholesterol, or retards the entire series of reactions between acetate and cholesterol.


1968 ◽  
Vol 46 (8) ◽  
pp. 859-863 ◽  
Author(s):  
B. B. Migicovsky

The supernatant from a homogenate of rat liver was incubated in a system containing 14C-acetate. The mixture was then saponified, the cholesterol isolated as the digitonide, and its radioactivity determined. When glycerol (water control) was a constituent of the incubation mixture, less radioactivity appeared in the digitonide. Under the same conditions, glycerol did not apparently inhibit the incorporation of 14C-mevalonate into liver cholesterol. When rats were given glycerol or glucose by mouth then 14C-acetate intraperitoneally, the total cholesterol radioactivity, specific radioactivity, and in most cases the serum cholesterol concentration, were all lower in those rats that had been given the glycerol.


1960 ◽  
Vol 21 (1) ◽  
pp. 25-32 ◽  
Author(s):  
G. S. BOYD ◽  
M. F. OLIVER

SUMMARY A series of twelve iodinated thyroxine analogues was studied for thyro-activity in the rat. Each analogue produced antigoitrogenic activity, increased oxygen consumption, heart rate and heart weight, and decreased serum and liver cholesterol levels. A 'serum cholesterol/heart rate ratio' may be computed for these analogues under fixed experimental conditions. While the dose-response curves for different analogues in any of these assays are rarely parallel, it is, nevertheless, clear that under certain experimental conditions some iodothyronines cause a relatively greater depression of cholesterol levels and less stimulation of heart rate than others. Some of the most active in this respect are DT4, DT3, DT2 and T4F.


1964 ◽  
Vol 207 (3) ◽  
pp. 631-633 ◽  
Author(s):  
David Kritchevsky ◽  
Shirley A. Tepper

Changes in serum cholesterol levels with age have been studied in male and female rats of three inbred strains (BN, DA, and Lewis) and one random-bred strain (Wistar). The mean serum cholesterol levels at each age differed among strains. Serum cholesterol levels (mg/100 ml) for male rats at 30, 60, and 90 days were: BN-65, 46, and 47; DA-105, 85, and 101; Lewis-79, 76, and 57; and Wistar-64, 63, and 73. For female rats the values were: BN-56, 45, and 47; DA-86, 74, and 91; Lewis-77, 83, and 67; and Wistar-59, 71, and 83. The variation of serum cholesterol with age was different between strains, but similar for males and females within each strain. There was no correlation between body weight and serum cholesterol. Liver cholesterol levels (mg/100 g) determined at 90 days were, for the males, BN-187, DA-233, Lewis-247, and Wistar-300, and for the females, BN-188, DA-244, Lewis-216, and Wistar-249. No correlation with body weight or serum cholesterol was observed.


1964 ◽  
Vol 42 (8) ◽  
pp. 1161-1168 ◽  
Author(s):  
P. J. Lupien ◽  
B. B. Migicovsky

Physiological disturbances common to B6 avitaminosis were clearly manifested when 3-day-old chicks were fed a pyridoxine-deficient diet for 8 days. Body and liver weights were depressed but were restored to quasi-normal states after 4 days of pyridoxine supplementation (3 mg/lb diet). The elevated serum cholesterol levels observed were the result of a failure of this parameter to fall at the rate characteristic of a well-fed bird and not to a specific elevation of the serum cholesterol above the starting conditions. Liver cholesterol levels were unaffected by the hypovitaminosis. Pyridoxine supplementation rapidly re-established normal serum cholesterol levels.The significant depression of C14-acetate incorporation into liver and serum cholesterol of 7-day-old pyridoxine-deficient chicks was maintained for the next 8 days. Mevalonate-2-C14 incorporation into liver cholesterol was not significantly depressed by the hypovitaminosis at any time during the study. Unlike the controls, mevalonate-2-C14 incorporation into serum cholesterol was significantly lowered in the 11-day-old pyridoxine-deficient chicks, but not at any other time during the study.The significance of these findings and the possible relationship between these factors are discussed.


1964 ◽  
Vol 42 (2) ◽  
pp. 179-185 ◽  
Author(s):  
P. J. Lupien ◽  
B. B. Migicovsky

The serum cholesterol level and the degree of incorporation of C14-acetate and C14-mevalonate into liver cholesterol has been studied in normal and deutectomized chicks.Serum and liver cholesterol levels in normal chicks decreased rapidly between 3 days and 5 days after hatching, and at 9 days of age the quantity of cholesterol stabilized at levels comparable to those of mature birds.Deutectomy significantly lowered serum cholesterol levels of the 5-day-old chicks but did not affect liver cholesterol levels.High levels of liver cholesterol in the 3-day-old chicks did not totally depress C14-acetate incorporation. Minimal C14-acetate incorporation was obtained when the chicks were 5 days of age and maximal incorporation occurred on the 15th day following hatching. C14-mevalonate incorporation into liver cholesterol was observed to be minimal when the chicks were 3 days of age and maximal when the chicks were 12 days of age.It is suggested that the chick might prove to be of value for the study of the control mechanisms in cholesterol metabolism.


1970 ◽  
Vol 118 (3) ◽  
pp. 519-530 ◽  
Author(s):  
I. W. Percy-Robb ◽  
G. S. Boyd

1. Isolated rat liver was perfused with heparinized whole blood under physiological pressure resulting in the secretion of bile at about the rate observed in vivo. 2. The preparation remained metabolically active for 4h and was apparently normal in function and microscopic appearance. 3. When the perfusate plasma and liver cholesterol pool was labelled by the introduction of [2-14C]mevalonic acid the specific radioactivity of the perfusate cholesterol increased. The biliary acids (cholic acid and chenodeoxycholic acid) were labelled and had the same specific radioactivity. 4. Livers removed from rats immediately after, and 40h after, the start of total biliary drainage, were perfused; increased excretion rates of both cholic acid and chenodeoxycholic acid were found when the liver donors had been subjected to biliary drainage. 5. The incorporation of [2-14C]mevalonic acid or rat lipoprotein labelled with [14C]cholesterol into bile acids was studied. 6. A dissociation between the mass of bile acid excreted and the rate of incorporation of 14C was found. This was attributed to the changing specific radioactivity of the cholesterol pool acting as the immediate bile acid precursor.


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