Serum Cholesterol Levels In Rats Research Articles

Effect of pantethine on cholesterol ester metabolism in rat arterial wall

The total serum cholesterol level in rats fed on a high cholesterol diet (HCD) for 16 weeks was markedly higher than that in rats fed on a normal diet (ND), but pantethine reduced the increased level in rats fed on HCD ( P < 0.05). Acid cholesterol esterase activity (acid CEase) of arterial wall homogenates from rats fed on HCD was significantly lower than that of rats fed on ND ( P < 0.005). Acid CEase activity in the arterial wall of rats fed on HCD for 8 weeks and then ND for 8 weeks was less than that of rats fed on ND for 16 weeks. Acid CEase activity in the arterial wall was increased in rats fed on pantethine-containing diet. The ratio of cholesterol ester synthesizing activity to neutral cholesterol esterase (neutral CEase) activity was higher in rats fed on HCD than in those fed on ND. The ratio was lower in rats on the pantethine-containing diet than in those on HCD. The relationship between hypercholesterolemia and lipid metabolism in the arterial wall and effects of pantethine are discussed on the basis of these results.

The effect of compactin, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme—A reductase activity, on cholesterogenesis and serum cholesterol levels in rats and chicks

Compactin, [7-(1,2,6,7,8,8a-hexahydro-2-methyl-8-(2-methylbutyryloxy) naphthyl)-3-hydroxyheptan-5-olide], a potent competitive inhibitor of the rate-determining step in cholesterol biosynthesis, was used to study the influence of changes in cholesterogenesis on serum cholesterol levels. Up to 3 h after a single oral dose (20 or 50 mg/kg) or after the last of a series of daily oral doses (50 mg/kg for 7 or 28 days) to young, male normolipid-aemic rats, compactin consistently inhibited cholesterogenesis measured using 3H 2O in liver, ileum and other extrahepatic tissues without affecting fatty acid synthesis. Compactin did not reduce serum or tissue cholesterol nor affect the serum concentration of other lipids nor the ratio between lipoprotein classes. A diurnal variation in the effect of compactin on cholesterogenesis was observed. For example, by 12–20 h after dosing, cholesterogenesis at all sites was increased above the comparable control value, indicating the induction of enzyme synthesis and overall there was little effect on the mass of cholesterol synthesized per day. Similar results were obtained using male chicks. Inhibition of cholesterogenesis by compactin was also observed in cholestyramine-treated rats, in which cholesterol turnover was markedly increased, and even in cholesterol-fed rats, in which cholesterogenesis already was repressed. In neither case, however, was inhibition of cholesterogenesis accompanied by a hypocholesterolaemic effect. It is concluded that a more persistent suppression of cholesterogenesis, than that observed with compactin in the rat, may be required in order to affect serum cholesterol concentrations.

パンテチンの抗動脈硬化作用について

Rats were fed in the following manner, 1) Normal diet for 16 weeks 2) High cholesterol diet for 8 weeks and then normal diet for 8 weeks 3) High cholesterol diet for 8 weeks and then normal diet plus pantethine for 8 weeks 4) High cholesterol diet for 16 weeks 5) High cholesterol duet for 8 weeks and then high cholesterol plus pantethine for 8 weeks 6) High cholesterol diet plus pantethine for 16 weeks. Serum cholesterol level in rats fed a high cholesterol diet for 16 weeks was considerably higher than in rats fed a normal diet for 16 weeks. The increased serum cholesterol was significantly lowered by administration of pantethine for 16 weeks or last 8 weeks. Acid cholesterol activity in rat arterial wall extract fed a high cholesterol diet was less than that in normal diet for 16 weeks. The activity in groups administered pantethine was increased more than that of controls. The ratio of cholesterol ester synthesizing activity to alkaline cholesterol esterase activity was increased in arterial wall extract from rats fed a high cholesterol diet for 16 weeks than in those from rats fed a normal diet for 16 weeks.The ratio in arterial wall extract from rats fed a high cholesterol diet administered pantethine for 16 weeks was lower than in those from rats fed a high cholesterol diet for 16 weeks. These results suggest that the deposition of cholesterol ester might be increased in lysosome or microsome of arterial wall and pantethine might protect the deposition.

Polyunsaturated fat, cholesterol and large bowel tumorigenesis

The possibility that the disposition of cholesterol, which is influenced by the quality of dietary fat, may be associated with either vascular lipidosis or colon cancer was evaluated in this study. Rats were fed diets containing cholesterol plus a) saturated fat, 20% coconut oil, to elevate serum cholesterol and promote vascular lipidosis or b) polyunsaturated fat, 20% safflower oil, to minimize serum cholesterol elevations and retard the development of vascular lipidosis. The relationships of these diets to gastrointestinal tract tumors induced by 1,2,-dimethylydrazine (DMH) was evaluated. Serum cholesterol levels in rats fed the coconut oil diet and given DMH were markedly elevated and were associated with moderate to severe vascular and aortic sudanophilia. Conversely, rats fed the safflower oil diet and given DMH had modest elevations in serum cholesterol levels and minimal vascular and aortic sudanophilia. Significantly, greater numbers of large bowel tumors induced by DMH were found in rats fed the safflower oil diet than in those fed the coconut oil diet. It was suggested that the polyunsaturated fat diet promoted the decrease in serum cholesterol levels concomitant with an increase in fecal neutral and acid sterols, which in turn augmented tumorigenesis by DMH in these animals compared with those fed the saturated fat diet. Thus, in the animal model used, the interaction of dietary fat (quality or quantity) with endogenous or dietary cholesterol determines whether or not diet will be a contributing factor in a) the development of vascular lipidosis or b) augmentation of small and large bowel tumorigenesis.

Utility of Fasting Essential Amino Acid Plasma Levels in Formulation of Nutritionally Adequate Diets III: Lowering of Rat Serum Cholesterol Levels by Lysine Supplementation

A lysine‐supplemented ration lowered the serum cholesterol levels of rats. The level of lysine supplementation was derived from the fasting plasma essential amino acid profile.

Effect of sodium hydrodextran sulfate on experimental arteriosclerosis in spontaneously hypertensive rats

In order to examine the effect of sodium hydrodextran sulfate (HDS) on experimental atherosclerosis spontaneously hypertensive rats (SHR) and normotensive Wistar rats (NR) were fed a high-fat diet with and without the drug. Blood samples were collected for 5 months to measure serum levels of cholesterol, triglyceride and clearing factor lipase activity. Effect of HDS on certain blood factors were as follows: 1) HDS inhibited the increase of serum cholesterol levels in rats. 2) HDS did not change the triglyceride concentration. 3) HDS elevated the clearing factor lipase activity. 4) A high-fat diet increased the intimal thickening of arteries in SHR. 5) Intimal thickening of arteries decreased slightly in the HDS treated group.

Interaction of Dietary Vitamin E and Protein Level or Lipid Source with Serum Cholesterol Level in Rats

Interaction of Dietary Vitamin E and Protein Level or Lipid Source with Serum Cholesterol Level in Rats

Influence of Strain Differences on Serum Cholesterol Levels in Rats

The purpose of this study was to clarify the relationship between rat strain and the serum cholesterol level.Wistar, Donryu and Sprague-Dawley strain rats of both sexes were divided into 2 groups and fed on the following two kinds of diet for 10 days; a standard diet not containing cholesterol and a cholesterol diet containing 1% cholesterol and 0.25% bile salts. After 10 days, the animals were fasted overnight and the serum total cholesterol level was measured.Wistar strain was very similar to the Donryu strain in respect of the serum cholesterol level. In both strains, serum cholesterol levels in rats placed on the standard diet were about 80mg/dl, regardless of sex. Dietary cholesterol caused a rather significant increase in serum cholesterol levels reaching 100-110mg/dl, regardless of strain or sex.Sprague-Dawley strain rats fed on the standard diet showed a higher serum cholesterol level (about 100mg/dl) than the Wistar or Donryu strains. When the Sprague-Dawley rats were placed on the cholesterol diet, a marked elevation in the serum cholesterol value was observed in the males (156mg/dl) and furthermore in the females (256mg/dl).Liver total cholesterol level of the Sprague-Dawley rats maintained on the cholesterol diet was also the highest among the three strains.

Anti-hypercholesterolemic effect of dehydroepiandrosterone in rats.

SummaryDehydroepiandrosterone (DHA) and 3α-methoxy − 17α−methyl− 5α −androstane−17α−01 (SC-12790) were studied for their anti-hypercholesterolemic and thyromimetic activities. The following findings were established: 1. DHA (5 mg/kg/d per os for 10 days) was found to be an anti-hypercholesterolemic agent which prevented increase in the serum cholesterol level (SCL) of rats made hypercholesterolemic by propylthiouracil (PTU) treatment. It was also found that the same dose of DHA given over a period of 21 days prevented an increase in SCL in rats made hypercholesterolemic by combined PTU and cholesterol feeding. DHA, however, did not reduce the SCL of normal rats. 2. SC-12790, when given under the same experimental conditions as DHA, did not reduce the SCL of hypercholesterolemic rats. 3. DHA did not produce any change in thyroid weight as did exogenous TSH and T-3. It seems that the anti-hypercholesterolemic effect of DHA cannot be explained by a thyromimetic activity. These findings are of clinical import...

EFFECT OF DIET, OF 3:5-DIIODO-D-THYRONINE AND OF 3:5-DIIODO-4(4′-HYDROXY PHENOXY) PHENYL ACETIC ACID ON THE FORMATION AND REGRESSION OF ATHEROSCLEROTIC LESIONS IN THE RAT

SUMMARY 1. Atherosclerotic lesions can be made to develop or regress in the albino rat by treatments that, respectively, elevate or depress the serum cholesterol concentration. 2. After young rats had been given a new diet for 45–72 days, the degree of atherosclerosis attained was related to the new serum cholesterol level and was independent of the previous degree and severity of atherosclerosis. 3. Regression of lesions established for about 1 month occurred if the serum cholesterol level was lowered, either by changes in the diet or by administering 3:5-diiodo-d-thyronine (DT2). The relation between serum cholesterol level and Sudan score (see p. 70) appeared to be independent of the method used for lowering the serum cholesterol level. 4. Regression of lesions established for about 6 months occurred if the serum cholesterol level was lowered either by changes in the diet or by administering DT2, but the rate of regression was slower than when the lesions had been present for a short time only. 5. When the serum cholesterol levels of rats given an atherogenic diet for 6 months had been reduced to normal values by feeding stock diet, the rats still had a high degree of atherosclerosis. When stock diet containing DT2 was then fed, there was no increase in the rate of regression of lesions over that obtained on the stock diet alone. 6. Dietary administration of different amounts of 3:5-diiodo-4(4′-hydroxy phenoxy) phenyl acetic acid (DIAC) or DT2 to groups of rats maintained on a diet containing cholesterol and cholic acid over a 9-month period resulted in a reduction of serum cholesterol levels to an extent roughly related to the dose of drug given. Liver cholesterol levels were also reduced in the older animals. Arterial atheroma was reduced by both compounds to an extent proportional to the dose administered. Both compounds, at all dose levels, increased the rate of growth of animals compared with that of controls. Both compounds depressed liver weights at all dose levels and increased the weight of the pancreas at the higher dose levels, if these weights were expressed per 100 g/body weight.

Oxidation of cholesterol-26-C14 by rat liver mitochondria: effect of nicotinic acid

The effect of nicotinic acid upon the oxidation of the terminal carbon atoms of cholesterol-26-C14 by rat liver mitochondrial preparations has been studied. Addition of nicotinic acid, as the potassium salt, to incubation mixtures containing normal rat liver mitochondria enhances the oxidation of cholesterol-26-C14. Liver mitochondrial preparations from rats administered nicotinic acid in drinking water (12 mg. per day) or diet (0.75 per cent) also oxidize cholesterol-26-C14 to a greater extent than do similar preparations from control rats. The mitochondrial preparations from nicotinic acid-fed rats, in the absence of boiled supernatant, exhibit a greater oxidative capacity than do control preparations. This heightened oxidative capacity is further enhanced by addition of the boiled supernatant fraction from these preparations. Addition of boiled supernatant from control preparations has no enhancing effect. Nicotinic acid exerts little effect on the oxidation of sodium pyruvate-2-C14 and may have a slightly inhibitory effect upon the oxidation of sodium octanoate-1-C14. No significant differences were observed between serum cholesterol levels of rats ingesting nicotinic acid for 3 weeks and controls.

Influence of dietary cod-liver oil and some fractions of cod-liver oil on serum cholesterol-level of rats.

FROM numerous experiments with humans and experimental animals it is known that the cholesterol content of the blood is greatly influenced by the amount and kind of dietary fat. In general, the relatively unsaturated vegetable fats decrease the serum cholesterol-level, while an increasing influence is observed with the relatively saturated animal fats. The highly unsaturated oils from marine animals, however, exert a potent cholesterol-lowering activity. This effect was observed in humans following the consumption of seal oil1, sardine oil2, whale oil3 and pilchard oil1,4 and also in rats fed sardine oil5.

Relationship of fluoride and dietary fats to serum cholesterol in rats.

SummarySerum cholesterol level was determined in 5 series of rats receiving either different fats in their diets or different fats plus fluoride to determine whether the use of fluoride is associated with an increased serum cholesterol level. After administration of 2 mg of fluoride daily throughout a 10-week period there was no significant change in serum cholesterol level of rats regardless of their dietary fat source or the presence of fluoride. Comparison of body weight gains of the various groups fails to suggest that any of the fats used resulted in increased fluoride toxicity.

The Quantitative Effects of Cholesterol, Cholic Acid and Type of Fat on Serum Cholesterol and Vascular Sudanophilia in the Rat

Marked differences in the effect of various oils on the serum cholesterol levels of rats fed diets containing cholic acid and cholesterol are readily measured with considerable accuracy. In general, the effects of the oils tested tend to be similar to their reported effects upon serum cholesterol levels in human beings, suggesting that the active factors in the two species may be similar. The rat assay may thus be a useful, rapid, and relatively accurate method for determining the effects of the various constituents of fats upon serum cholesterol levels. In general, the highly unsaturated oils result in lower serum cholesterol levels. Tung oil, rich in eleostearic acid, is a marked exception and produced the highest serum cholesterol levels of any oil tested. Admixture with corn oil counteracts this hypercholesteremic activity in proportion to the amount of corn oil added. The effect of varying levels of cholic acid and cholesterol on serum cholesterol levels has been quantitated in two different oils. With all oils and at various levels of cholic acid and cholesterol, the amount of Sudanophilic material under the endothelium was proportional to the mean serum cholesterol level. The “atherogenic” activity thus appears to be mediated through the serum cholesterol levels.