Dissolution of gallstones in hamsters by 3-hydroxy-3-methylglutaric acid.
Addition of 0.05--0.20% of 3-hydroxy-3-methylglutaric acid to a lithogenic hamster diet resulted in a marked reduction in the incidence of gallstones in hamsters.
Biomedical subjects
Publications and source records attributed to D Kritchevsky.
Addition of 0.05--0.20% of 3-hydroxy-3-methylglutaric acid to a lithogenic hamster diet resulted in a marked reduction in the incidence of gallstones in hamsters.
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Epidemiological data suggest that populations subsisting on high fiber diets are free of a number of the diseases of Western civilization, among them coronary heart disease. Studies in animals and man show that each type of fiber exerts its own specific influence. Thus, in man bran has no effect on serum lipids, but pectin lowers cholesterol levels. In animals fed atherogenic diets, alfalfa and pectin exert some measure of protection, but cellulose does not. To fully understand the mode of action of dietary fiber, it is necessary to ascertain the mechanism(s) of action of each chemical component of that fiber.
Fiber, when fed to animals or man, will generally cause increased excretion of bile acids. The level of bile acid excretion appears to be a function of the structure of the fiber. Fiber binds bile acids and bile salts in vitro. The extent of binding is characteristic for each type of fiber and each substrate. Bile acid binding may be one mechanism of the physiological action of fiber.
Rabbits were fed an atherogenic diet (2% cholesterol and 6% corn oil) for 8 weeks and then divided into groups of equal average serum cholesterol levels. One group was autopsied, and the others were returned to cholesterol-free diets consisting of commercial laboratory ration or ration augmented with 6% corn oil, peanut oil or PGF, a fat designed to resemble peanut oil minus arachidic and behenic acids. The animals were maintained on the diets for 8 more weeks. On all regimens, severity of atherosclerosis was exacerbated. The extent of exacerbation was significantly less in rabbits fed corn oil than in the others. The extent of exacerbation of lesions appears to be a function of the level of unsaturation of the dietary fats.
The in vitro activity of cholesteryl ester hydrolase preparations of rat and rabbit aortas was assayed in the presence of the taurine and glycine conjugates of cholic, chenodeoxycholic, deoxycholic and lithocholic acids or in the presence of Triton X-100 and Tween-20. Maximum activity was obtained with tauro- or glycocholic acids. As in the case of pancreatic cholesteryl esterase, trihydroxycholanoic acid derivatives may serve an obligatory function.
The lipoproteins of young and old Wistar rats differ markedly in distribution and chemical composition. The major differences are: (1) the presence of high levels of free and esterified cholesterol, triglycerides and free fatty acids in the lipoproteins of old rat plasma when lipids are analyzed/100 ml of plasma. However, the ratio of total cholesterol to protein mass indicates the presence of comparable cholesterol pools in all lipoprotein fractions of young and old rats excepting the d 1.063--1.21 fraction where a higher cholesterol pool in old rats is indicated. (2) The amount of sphingomyelin increases in lipoprotein fractions of old rat plasma thereby actually decreasing the lecithin/sphingomyelin ratio in these plasma fractions. (2) Unsaturated fatty acids predominate in young rat plasma lipoproteins, and saturated fatty acids predominate in old rat lipoprotein fractions. The ratio of polyunsaturated (linoleic, linolenic, arachidonic) to saturated (palmitic, stearic) fatty acids in young rat sera was 0.89 and in old rat sera, 0.55.
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Studies in experimental animals and in humans have shown a definite interaction of dietary fiber with bile acid metabolism. In experimental animals, some types of fiber have been shown to increase bile acid excretion as well as increase pool size and turnover of bile acids. In man, increases in bile acid excretion have been observed but not consistently. Alternations in excretion and biliary bile acid levels indicate an influence of dietary fiber in bile acid metabolism. In vitro experiments have attempted to determine the nature of the fiber-bile acid interaction. Some types of fiber and some components of fiber have been shown to bind bile acids and bile salts in appreciable quantities. The capacity for various types of fiber to bind bile acids or bile salts is quite variable, and a high capacity seems to correspond with a hypocholesteremic effect. A great deal of research is still needed for elucidation of these interactions of fiber and bile acid metabolism and the resultant beneficial effects on cholesterol metabolism and the disease-related abnormalities in cholesterol metabolism.
The indirect effects of short-term (3-day) feeding of several types of dietary fiber and nonnutritive materials on the subsequent absorption of cholesterol has been investigated in thoracic duct cannulated rats. Absorption was studied at timed intervals over 24 hr after duodenal introduction of a tracer dose of cholesterol at least 20 hr after the last feeding. In animals fed for 3 days with diets containing cholestryamine, bran, or cellulose, cholesterol absorption was significantly less than in control animals maintained on rat chow. Rats fed for 3 days with an alfalfa-containing diet showed large variations in cholesterol absorption that were not significantly different from controls. However, after 5 weeks, rats on the alfalfa diet showed a marked reduction in lymphatic absorption of the tracer sterol. These indirect effects of cholestryamine and fibers on cholesterol absorption were not attributable to a common mechanism; i.e., differences in transit times that were not significant, or dirrect binding of bile acids and cholesterol by the test materials.
The influence of dietary fiber on lipid metabolism and atherosclerosis in animals and on lipid metabolism in man is reviewed. Pectin, guar gum, and lignin lower serum and liver cholesterol in cholesterol-fed rats. Agar increases liver cholesterol in rats. Bran has no effect on serum lipid levels in rats or monkeys. Vegetarians have long been known to exhibit cholesterol levels lower than those of comparable populations who subsist on a mixed diet. Pectin and guar gum lower cholesterol levels in man whereas cellulose and bran have no effect. Rabbits fed a semipurified diet containing saturated fat become atherosclerotic, but addition of the same fat to laboratory ration has no effect; it has been shown that the residue in laboratory ration is the cause of the difference. Semipurified diets containing cellulose are more atherogenic than those containing wheat straw or alfalfa. The semipurified diets also cause aortic sudanophilia or atherosclerosis in baboons and vervet monkeys. One possible mechanism of hypolipemic action of fiber involves the binding of bile acids, which would result in reduced absorption of cholesterol, resulting in lower levels of serum cholesterol.
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The activity of N-acetyl hexosaminidase (beta-2-acetamido-2-deoxy-D-glucoside:N-acetamido-deoxyglucohydrolase, E.C. 3.2.1.30) was significantly greater in sera of patients with solid malignant tumors than in sera of healthy volunteers or of patients with nonmalignant ailments. The increased activity was found in the two major isozymes, hexosaminidase A and hexosaminidase B, but the increase in the latter isozyme was more prominent than in the former. Measurement of the levels of the hexosaminidase isozymes may provide an ancillary diagnostic test for malignancy.
We describe a method for determining free and total cholesterol in extracts of rat-liver lipids by use of a cholesterol esterase/cholesterol oxidase enzymatic kit (Boehringer Mannheim Corp). The lipids are solubilized (as micelles) directly into the aqueous reagent mixture. Results of the enzymatic method correlate well with those obtained by an acid/ferric chloride assay of digitonin precipitates of the extracts. The enzymatic assay of free and total cholesterol in tissue offers advantages of simplicity over previously used methods.
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In studies of hydrolysis and synthesis of cholesterol esters by aortic enzymes, conventional methods (aside from isotope methodology) are too insensitive to measure reaction products when few aortas are used. High-performance thin-layer chromatography coupled with spectrodensitometry of plates charred after spraying with a cupric acetate-phosphoric acid reagent permitted quantitation of 10-ng amounts of cholesterol, cholesterol oleate oleate, and oleic acid. Linear calibration curves were obtained after spectrodensitometry of chromatograms containing 10-200 ng of lipid. The results were verified by radioassay.
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