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Biomedical subjects

D Kritchevsky

Publications and source records attributed to D Kritchevsky.

At least 253 records · Page 14Linked to original sources

Cholesteryl ester metabolism in tissue culture cells: II. Source of accumulated esterified cholesterol in Fu5AH rat hepatoma cells.

Previous investigations had demonstrated that Fu5AH rat hepatoma cells accumulated large quantities of esterified cholesterol when grown in hyperlipemic rabbit serum. The present investigation has determined the sources of the cellular esterified cholesterol when the cells were grown in hyperlipemic serum. Cellular esterification of endogenous and exogenous free cholesterol contributed 10% and 30%, respectively. The remaining 60% of the accumulated cellular esterfied cholesterol was derived from exogenous (serum) cholesteryl esters. Evidence for the hydrolysis of a portion of the incorporated esterified cholesterol is presented. A stimulation of free cholesterol incorporation and cellular esterification is elicited by hyperlipemic serum and serum lipoproteins when compared to normolipemic serum present at equivalent exogenous cholesterol concentrations. The effect of hyperlipemic serum is reduced by Tween-80 and Triton WR-1339. Comparative data on esterified cholesterol accumulation, free cholesterol incorporation, and cellular cholesterol esterification in Fu5-5 rat hepatoma cells, L-cells, and rabbit aortic medial cells are presented.

Animals↗

Age-related changes in the lipid metabolism of Fisher 344 rats.

Lipid metabolism of male Fisher 344 rats aged 2-24 months was studied. Serum and liver cholesterol levels did not display the age-related gradual increase seen in other rat strains. An increase in the serum plus liver cholesterol pool from 2 to 6 months was followed by a plateau through 18 months and then another increase at 24 months of age. The triglyceride pool increased from 2 to 6 months and then remained unchanged through 24 months of age. Cholesterol synthesis from acetate decreased 50% between 2 and 9 months and fell only slightly through 24 months of age. Assay of 3-hydroxy-3-methyl glutaryl Coenzyme A (HMG-CoA) reductase showed a similar pattern but did not decrease further after 9 months of age. Cholesterol 7alpha hydroxylase activity was not significantly altered by age. These age- and strain-related differences present an opportunity for a comparative study of the aging process using the parameters of lipid metabolism as indicators.

Acetates↗

Comparison of the binding of various bile acids and bile salts in vitro by several types of fiber.

The binding in vitro of the sodium salts of cholic acid, chenodeoxycholic acid, deoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, and glycodeoxycholic acid by alfalfa, bran, cellulose, lignin, and cholestyramine was measured. Cholestyramine bound an average of 81.3% of all the bile acids and salts tested whereas cellulose bound only negligible amounts (1.4%). Of the other substances tested, lignin bound 29.2%, alfalfa, 15.9% and bran, 9.0%. No distinct pattern of binding was discerned. It is therefore apparent that the validity of statements concerning the effect of fiber on bile salf metabolism rests upon the specificity of the composition of the fiber involved and the bile acids or salts tested.

Bile Acids and Salts↗

Influence of ketamine, phenylcyclidine, and phenobarbital on cholesterol metabolism in rats.

The effects of ip injections of phenobarbital (100 mg/kg), phenylcyclidine (Sernylan; [1-(1-phenylcyclohexyl)-piperidine-HBl] (1 mg/kg), and ketamine (Ketaset; [dl)2-O-chlorophenyl)-2-(methylamino)cyclohexanone-HCl] (1 mg/kg) on lipid metabolism in rats were compared. This study was undertaken to determine whether the two sedatives currently used in primates share any of the undesirable effects of phenobarbital on lipid metabolism. All three compounds were administered to male Wistar rats for 6 days. Phenobarbital was hepatomegalic, stimulated 7alpha hydroxylation of cholesterol, and inhibited cholesterol synthesis by rat liver slices from mevalonate, but not acetate. The two other sedatives exhibited effects very similar to those observed in the controls. From our work in rats it is concluded that the use of Sernylan or Ketaset for sedation of nonhuman primates will not significantly affect these parameters of lipid metabolism.

Animals↗

Diet and atherosclerosis.

Because of the statistical establishment of elevated blood lipids as a risk factor in the development of atherosclerotic heart disease, most of the attempts to regulate blood lipids by diet are centered on the fat in the diet. The levels of blood lipids and the course of experimental atherosclerosis can be affected by other dietary components such as type and amount of protein, carbohydrate, and nonnutritive fiber. Interaction among the dietary components further affects serum lipids and atherosclerosis.

Animals↗

Influence of four agents (tibric acid, DH 990, oxandrolone and Sch 9122) on aspects of lipid metabolism in rats).

We have investigated the effects of four drugs on aspects of lipid metabolism in rats. The four drugs used were: tibric acid = 2-chloro-5-(cis--3,5-dimethylpiperidonosulfonyl)benzoic acid; DH 990 = 2-[(3,5-di-t-butyl-4-hy-droxyphenyl)thio]hexanoic acid; oxandrolone = 17beta-hydroxyphenyl-17a-methyl-2-oxa-5a-androstan-3-one; and Sch 9122=2-(p-anisyl)-3(2-pyridyl)pentane hydrochloride. Serum and liver triglycerides and liver cholesterol, 7a-hydroxylase and 26-oxidase were determined. Tibric acid (0.015%) was hepatomegalic and hypotriglyceridemic. It did not affect normal 7a-hydroxylase or 26-oxidase activity. In the absence of cytosal, this drug resulted in normal mitochondrial cholesterol-26-oxidase activity whereas none was observed with preparations from control rats. DH 990 (0.075%) did not affect liver size. It had a slight (10--20%) hypolipidemic effect. The effects of DH 990 on the two liver enzymes were similar to those of tibric acid. In view of the absence of a hepatomegalic effect of DH 990, its influence on mitochondrial oxidation of cholesterol in the absence of cytosol is noteworthy. Oxandrolone (0.15%) had a slight (11%) hepatomegalic effect but did not influence serum of liver lipid levels. This drug caused a 19% increase in liver 7a-hydroxylase activity but did not affect cholesterol-26-oxidase activity in the presence or absence of cytosol. Sch 9122 (0.03%) caused significant weight loss. Serum and liver cholesterol levels were unaffected, but serum triglyceride levels were significantly elevated in rats fed this drug. Cholesterol-7a-hydroxylase activity was slightly (11%) higher than normal, but 26-oxidase was significantly lower.

Animals↗

The effects of feeding various carbohydrates on the development of hypercholesterolemia and atherosclerosis.

It is possible to establish atherosclerosis in rabbits by feeding semi-synthetic diets that are high in carbohydrate and saturated fat and devoid of cholesterol. Addition of saturated fat to laboratory chow does not render the chow atherogenic. When rabbits were fed diets which differ only in the carbohydrate component, starch was found to be more atherogenic than sucrose which, in turn, was more atherogenic than glucose. All the diets were hypercholesteremic and hypertriglyceridemic. In another series of experiments diets containing fructose or sucrose were more atherogenic than diets containing glucose, lactose or sorbitol. Baboons were feed semi-synthetic diets containing fructose, sucrose, starch or glucose (but no cholesterol) for one year. Serum cholesterol levels were 155-165 mg/dl in all test groups. The normal baboon cholesterol level is 115 mg/dl. Serum triglycerides were elevated from the normal level of 73 mg/dl to about 110 mg/dl in the groups fed starch and glucose and to about 125 mg/dl in the groups fed fructose and sucrose. Liver and lung cholesterol ester levels were also raised. The test groups all showed aortic sudanophilia. The most severe sudanophilia was observed in the fructose group (11.2% of surface area) and the least in the glucose group (6.2% of surface area). The biliary cholesterol specific activities (after administration of (3-H)-melvalonic acid) were the same in all groups, but biliary bile acid specific activity was higher in the control baboons than in test animals. These data, plus the higher primary/secondary bile acid ratio observed in the test animals, suggest that reduced bile acid synthesis may be one cause of the hypercholesteremia observed in animals fed the semi-synthetic diets.

Animals↗

Influence of an eggplant (Solanum melongena) preparation on cholesterol metabolism in rats).

To investigate the mechanism behind the hypocholesteremic properties of Solanum melongena diets containing 1% Sol. mel. leaf or fruit powder, alfalfa, or clofibrate were fed to rats. Sol. mel. did n ot lower the serum plus liver cholesterol pool of rats, whereas alfalfa and clofibrate did. However, all substances tested decreased the absorption of a single dietary dose of [4-14C] cholesterol. It appears that Sol. mel. exerts its reported hypocholesteremic effect in rabbits through an inhibition of absorption of dietary cholesterol. This inhibition is probably brought about partially through the binding of bile salts which are essential for cholesterol absorption.

Animals↗