Bile Of Animals Research Articles

Impaired hepatic disposition of sulfobromophthalein sodium in neonatal guinea pigs: nature of the defect.

Abstract Hepatic disposition of sulfobromophthalein sodium (BSP) was studied in newborn guinea pigs from the second to the sixteenth day of life after intravenous administration of doses of unconjugated and conjugated dye sufficient to achieve maximal rates of dye excretion into bile. Neonatal guinea pigs injected with unconjugated BSP showed a marked reduction in the maximal rate of dye excretion into bile when compared to adult animals given comparable weight-adjusted doses of unconjugated BSP. A minimal estimate of hepatic uptake of unconjugated dye revealed uptake to be comparable in neonatal and adult animals and significantly greater than maximal rates of dye excretion into bile; hepatic uptake did not limit hepatic disposition of unconjugated dye. Analysis of BSP compounds in the bile of these animals revealed that both unconjugated and conjugated dye appeared in decreased amounts. With aging, injected unconjugated dye was excreted at progressively more rapid rates. This was accounted for by almost proportionate increases in output of both unconjugated and conjugated forms of the dye. Quantitatively, increased output of unconjugated BSP into bile was the major factor accounting for improvement in dye excretion in neonatal animals infused with unconjugated BSP. By contrast, neonatal animals from the second day of life excreted injected conjugated BSP into bile as readily as adult guinea pigs. The studies are interpreted as indicating that impaired hepatic disposition of injected unconjugated BSP in the neonatal guinea pig is due to a combination of decreased transport of unconjugated dye from liver cells into bile, and decreased conjugation of BSP.

Endrin and dieldrin: A comparison of hepatic excretion in the rat

The excretion of radioactivity from radiolabeled endrin and dieldrin, chlorinated hydrocarbon insecticide stereoisomers, has been compared in whole rats, bile-fistula rats, and isolated perfused rat livers. Male Holtzman rats, with and without bile fistulas were given intravenous doses (0.25 mg/kg) of endrin- 14C or dieldrin- 14C. Urine and feces were collected daily. Bile was collected at 1, 3, 6, 12, and 24 hours and daily thereafter. The animals were maintained for 5–7 days, then were sacrificed. Isolated, perfused rat liver experiments were performed with radiolabeled insecticides in the perfusates (0.003 or 0.0003 mg/ml). Bile and perfusate were sampled hourly. The liver was sampled at the end of the 4–6-hour experiment. Radioactivity in all excreta, carcasses, bile, perfusates, and liver tissue was measured by liquid scintillation counting. Over 90% of the excreted activity was found in the feces of the intact animals and in the bile of fistula animals. The cumulative mean daily excretion of radioactivity from endrin was greater than that from dieldrin in the feces of intact animals, bile of bile-fistula animals, and bile of isolated, perfused rat liver preparations. The more rapid fecal elimination of endrin can be explained by its more rapid biliary excretion. Intestinal absorption and fatty tissue sequestration have been excluded as major factors, and the liver has been identified as the source of the difference. These results may explain the greater storage of dieldrin in the body fat of mammals.

Enterohepatic circulation of cholic acid and cholesterol metabolism in the rat.

AbstractA role for cholic acid in the regulation of body cholesterol levels is emphasized by the following experiment and findings. Fifteen rats with biliary and duodenal fistulae were divided into three groups. 4‐14C‐cholesterol was admistered intravenously to all animals on day 1. Two groups received a duodenal infusion of either sodium taurocholate or of cholesterol at the same time and thereafter daily. Bile samples were collected daily for 15 consecutive days. Cholic, chenode‐oxycholic acid and cholesterol were the major labeled compounds in the bile. Labeled cholic acid disappeared from the bile of control animals after day 8 while it persisted in the group receiving unlabeled cholic acid up to day 15. The decrease of specific radioactivity of labeled biliary cholic acid in the rats receiving unlabeled cholesterol corresponded to that of control animals. A significant increase in the concentration of cholesterol was found in the plasma of animals receiving cholic acid and in the liver of those receiving unlabeled cholesterol.

The mode of excretion and metabolic fate of potassium naphthyl 2- 35S-sulphate and potassium 5,6,7,8-tetrahydronaphthyl 2- 35S-sulphate

The metabolic fates and modes of excretion of naphthyl 2- 35S-sulphate and 5,6,7,8-tetrahydronaphthyl 2- 35S-sulphate were investigated in the rat. Only small amounts of administered radioactivity were present in the bile of animals receiving the esters and in both cases the major proportion of the radioactive dose appeared in the urine. The bulk of the urinary radioactivity following naphthyl 2- 35S-sulphate administration was identified as unchanged parent ester. Urines obtained from animals receiving 5,6,7,8-tetrahydronaphthyl 2- 35S-sulphate also contained large quantities of unchanged parent ester. However, such urines also contained significant quantities of other radioactive components. The significance of the results is discussed in relation to the structural difference between naphthyl 2- 35S-sulphate and 5,6,7,8-tetrahydro-naphthyl 2- 35S-sulphate.

Composition of bile acids in ruminants

The bile acids found in sheep bile, beef bile, beef feces, sheep fetus bile, and beef fetus bile have been analyzed by using conventional techniques. Animals maintained on natural and purified diets were used. The bile acids are a complex mixture of isomeric hydroxy- and keto-5beta-cholanoic acids which were substituted at one or several of the carbon atoms 3, 7, and 12. Cholic acid is the predominant bile acid found in these species. Deoxycholic acid was the major product formed from cholic acid when the animals were on a natural diet but the concentration of 3alpha, 12alpha-dihydroxy-7-keto-5beta-cholanoic acid was elevated in the animals that were maintained on a high concentrated purified diet (without roughage). The fetus bile was found to contain nearly all of the bile acids found in the bile of the mature animal but in different concentrations.

Absorption of Taurocholate-24-14C Through the Canine Gastric Mucosa.

SummaryWhen neutral solutions of natural dog bile or of synthetic taurocholate labeled with chromatographically pure taurocholate-24-14C were placed in pouches of the oxyntic gland area of the dog's stomach, total radioactivity decreased. Calculated rate of absorption of taurocholate was greater the higher the concentration of taurocholate in the pouch, and it ranged from 12 to 304 μM per hour. That bile salt can be absorbed from the stomach into venous blood was shown by the fact that when the stomach of an anesthetized dog was filled with a neutral solution of 10 mM bile salts derived from dog bile and labeled with taurocholate-24-14C, radioactivity appeared in the fluid collected by cannulation of the animal's bile duct.

Stability of cholesterol in animal bile

Stability of cholesterol in animal bile

THE FATE OF 2,4,6-TRI-(3',5'-DI-TERT.-BUTYL-4'-HYDROXYBENZYL)MESITYLENE (IONOX 330) IN THE DOG AND RAT.

1. Unchanged Ionox 330 is quantitatively eliminated in the faeces of dogs, rats and man after oral administration, and (14)C is absent from the urine and expired gases of rats intubated with [(14)C]Ionox 330. Dogs and rats do not show a sex difference in this pattern of elimination. 2. Quantitative elimination of [(14)C]Ionox 330 and the absence of (14)C in the carcass and viscera of rats 72hr. after dosage show that this substance does not accumulate in the body. 3. No metabolites are formed in consequence of the ingestion of Ionox 330. 4. Rats eliminate three-quarters or more of a dose (285.7mg./kg. body wt.) of Ionox 330 in 24hr. and the remainder during 24-48hr., and dogs eliminate the whole dose (90mg./kg. body wt.) within 48hr. and a variable proportion within 24hr. These rates of elimination are consistent with the passage of unabsorbed material through the alimentary canal. 5. After removal of the alimentary canal, radioactivity is absent from the carcass and remaining viscera of rats 8, 16 and 24hr. after ingestion of [(14)C]Ionox 330, and this strongly suggests the absence of alimentary absorption. 6. The absence of (14)C in the 24hr. bile of animals with biliary fistulae establishes that [(14)C]Ionox 330 is not absorbed from the gastro-intestinal tract.

GAS-LIQUID CHROMATOGRAPHY OF BILE ACIDS.

AbstractMethods are reviewed for the preparation, gasliquid chromatographic (GLC) separation, identification, and quantitative estimation of the trifluoroacetyl derivatives of bile acid methyl esters. Of the stationary phases tried (SE‐30, QF‐1 and XE‐60) methylfluoroalkyl silicone (QF‐1) was best suited for analysis of the trifluoroacetates. This phase (1舑2% QF‐1 on 100舑120 mesh Gas Chrom P) allowed an orderly resolution of conformational isomers and consistently gave GLC columns (stainless steel tubes, 1/8 in. O.D. ȕ 3 ft) from which the bile acid derivatives could be recovered in high yield. Applications to biological materials are illustrated with bile acid samples from animal biles and from human duodenal drainage and feces. Identifications of the major bile acids made by the GLC of the trifluoroacetates were confirmed by results obtained with bile acid methyl esters and bile acid methyl ester acetates on QF‐1 and the other liquid phases investigated. For most mixtures of bile acids, however, it appears that GLC of methyl esters and methyl ester trifluoroacetates on QF‐1 is sufficient for a reliable recognition of common bile acids. Overall accuracy of the estimates was of the order of ŷ 5%, but it varied with the nature and concn of the component.

Toxicity of Lithocholic Acid for the Chick

Abstract Lithocholic acid is considered to be a metabolite derived from chenodeoxycholic acid by intestinal bacteria during enterohepatic circulation (Norman and Sjovall, 1960) and traces of this substance are normally found in the intestine and in the bile of most animals. Edwards (1961) reported that feeding of 0.2% lithocholic acid to chicks results in a threefold rise in serum cholesterol and in a reduction of growth. When fed to laying hens, the bile acid not only causes hypercholesterolemia but also an abrupt decrease in egg production (Edwards et al., 1962). This effect on serum cholesterol in the chick is opposite to that observed in other animals. In mice and rats, lithocholic acid decreases serum cholesterol levels and counteracts the hypercholesterolemic effect of cholic acid (Howe et al., 1960; Howe and Hutchison, 1962). During the preparation of this manuscript Leveille et al. (1962) reported a twofold increase in liver size in chicks…

Continuous perfusion of bile and protease activators through the pancreas.

INVESTIGATIONSto the reflux of bile as a factor in pancreatitis by techniques which involve direct cannulation of the pancreatic duct and the injection of bile and other substances into the gland are subject to numerous inconsistencies and criticisms. 1,2 To obviate some of these problems, methods have been described in the dog and the goat for the in vivo perfusion of the gland at pressures which are not artificial. 2-5 In these techniques all of the animal's bile is perfused through the gland. It has been stated 5 that this technique of in vivo perfusion allows for the mixing of bile salts and activated trypsin to occur within the pancreas. 6 Recently, however, the suggestion was advanced that bile is not only a relatively poor protease activator but may actually afford some protection in vivo against protease auto activation. 2 In the present study a model was prepared in

Effect of polyunsaturated and saturated fatty acids on the cholesterol holding capacity of human bile.

The key to the prevention of gallstones or to the dissolution of stones already in existence probably lies in rendering hepatic bile unsaturated with respect to cholesterol. Cholesterol comprises 80%-100% of the commonly encountered gallstones. Comparative vertebrate biochemistry has shown that the bile of most animals can carry in solution considerably more cholesterol than is normally present; in man, however, the bile is practically saturated with cholesterol. For example, human bile can normally carry 15 to 25 mg.% additional cholesterol in solution, while the cholesterol-holding capacity (CHC) of dog bile is 120 mg.%. Not only are most animals free of stones, but human stones placed in their gallbladders undergo dissolution.1,2Also, some cases of spontaneous disappearance of gallstones in man have been reported.3,4 In theory, CHC might be increased either by lowering the cholesterol content of bile, while keeping its other constituents unchanged, or by increasing the concentrations

Medical and biochemical application of infrated spectroscopy. VII.Studies on various animal bile by infrated spectra and some of its pharmaceutical application, including indentification of the bear bile (Yutan).

Medical and biochemical application of infrated spectroscopy. VII.Studies on various animal bile by infrated spectra and some of its pharmaceutical application, including indentification of the bear bile (Yutan).

Gallen und Gallensäuren Papierchromatographische Untersuchungen

In cases of bile-scretion disturbances substitution-therapy can be performed using suitable animal biles equivalent to human bile. Comparative investigations have been made to establish which animal bile is in practice the most suitable for bile substitutiontherapy based on its bile acid components. A new paper partition chromatographic method has been applied for separation and identification of free bile acids. Ascending development was used on Schleicher & Schüll 2043b Mgl paper impregnated with 20 v/v% propylene glycol in chloroform. The xylene-methylethylketone 1:1 solvent system gave good separation. The bile acids can be detected by immersing the chromatograms in 20 w/v% SbCl3 in chloroform followed by drying and heating for 5–10 min at 100–110°C. The spots show intense reddish-violet or blue fluorescence in filtered UV-light (see Table 1). These investigations have shown that human and ox biles are, in contrast to pig bile, physiologically related biological substances regarding their bile acid components.

Syntheses of Cortisone and Related teroids

Publisher Summary This chapter discusses the variety of starting materials, which have been converted to cortisone. The automatic limitation of the starting material—animal bile—and the more or less fixed number of chemical steps represent a very considerable handicap. In a completely chemical process, sarmentogenin of all the plant steroids might well be the most attractive one, but the supply situation appears to be so hopeless and the question of cultivation so difficult that it is certain that sarmentogenin will not be employed. Hecogenin possesses the advantage that it contains a 12-keto group as well as the readily degradable sapogenin side chain, but so far no plant sources have been discovered, which contain more than approximately 1% hecogenin. Diosgenin and ergosterol are probably the most promising starting materials, the former possessing the spiroketal system so useful for degradation to the pregnane skeleton, and the latter possessing the ∆ 5,7 -diene system, which so far has proved to be essential for the chemical introduction of the 11-oxygen function into a ring C-unsubstituted steroid.

Cardiotonic activity of certain steroids and bile salts.

The effects of 23 plant and animal steroids, steroid hormones, and bile acids, and nine of their salts or soluble conjugates, have been investigated in isolated frog hearts. All but five of the compounds produced significant augmentation of frog hearts made hypodynamic by prolonged perfusion. The augmentation was not usually accompanied by changes in heart rate, and no steroid caused systolic arrest. Eight water-soluble steroid salts were perfused through isolated rabbit hearts when they had become hypodynamic by prolonged perfusion. In each case the coronary flow increased significantly whether the heart rate and force of contraction increased or not. Thus, when cardiotonic activity was observed, it appeared to be a direct effect and not secondary to the increased coronary flow. It would seem that the lactone ring of the cardiac glycoside molecule is responsible for the development of systolic arrest, and that the cardiotonic action is, at least partly, a function of the cyclopentenophenanthrene nucleus.

THE DISTRIBUTION AND STORAGE OF BLUE ANTIGENIC AZOPROTEINS IN THE TISSUES OF MICE

Intensely blue dye-azoproteins have been prepared by diazotization and coupling of the highly indiffusible blue dye T-1824, Evans blue, with various serum proteins and egg albumin. The products, whether purified by precipitation with alcohol or by chromatography, have a constant dye-to-protein ratio and tests have shown them to be essentially free from unlinked dye. An extremely diffusible dye, echt-säure-blau, has also been coupled to bovine gamma-globulin. These materials are adapted to physiological experimentation. They seem to behave in the bodies of mice like other proteins; they fail to appear in either the bile or urine of normal animals, and they are strongly antigenic. When these soluble antigenic azoproteins are injected into the blood stream of mice for the first time they enter reticulo-endothelial cells in almost every organ of the body; the final distribution is like that of intravenously injected, finely divided particulate matter. The azoproteins appear in the cells which classical immunological studies have shown to be active in removing particulate antigenic materials or bacteria from the blood or body fluids. The Kupffer cells of the liver and sinus and reticular cells in lymph nodes, especially the great mesenteric node, are particularly active in the removal of the blue antigens from the blood, but many other R-E cells are active to a lesser degree. The storage of the antigenic material is in the cytoplasm only; it has not been seen within nuclei, nor has it been seen within cells of the brain. Serological methods disclose that the blue material seen within Kupffer cells of the liver after as long a period as 2 days is still antigenic in its reactions. The blue azoproteins, therefore, serve excellently as tracer antigens, especially since they can be seen directly in fresh and fixed tissue preparations and in the body fluids.

Metabolism of 3,4-Benzpyrene in Mice

IF 3,4-benzpyrene is introduced into a mouse, it is eventually excreted as the phenol 8-hydroxy-benzpyrene1,2. It has been established that this transformation proceeds by various steps3,4. Four different benzpyrene derivatives have now been separated from extracts of various fresh tissues; they are provisionally termed X1, X2, F1 and F2, because they are responsible for the 'BPX' and 'BPF' fluorescences that Peacock5 and Chalmers6 discovered in the liver, bile, intestine and faeces of various animals after application of benzpyrene. The separation of X1, X2, F1 and F2 has been effected by fluorescence chromatography and selective extraction, using alumina and silica as adsorbents and acetone, benzene, xylene, petroleum ether, methyl, ethyl and amyl alcohols and water as solvents. X1 and X2 occur in vivo not only in the liver and digestive system but also in the lung, kidney cortex, subcutaneous tissue, skin (after painting with benzpyrene), and in the mammary glands as evidenced by the milk of mice; F1 and F2 occur in the large intestine and faeces, and occasionally in the lungs. The amount of fresh uncontaminated mouse urine did not suffice for a definite analysis, but there were indications of the presence of the X derivatives. Post mortem, all X-bearing tissues show slowly increasing amounts of the F derivatives unless they are kept in formol. The 3,4-benzpyrene-5,8-quinone that Berenblum and Schoental2 discovered in the faeces never appeared in fresh tissues.

RELATION OF FATTY ACIDS AND BILE SALTS TO THE FORMATION OF GALLSTONES

In a previous report1some of the chemical differences between the bile of certain domestic animals and that of human beings were discussed. By fractionating the bile of the dog and sheep, animals in which gallstones are not formed ordinarily, it was observed that the cholesterol solvent capacity of the bile could be isolated in the saponifiable or fatty acid fraction. Quantitative analysis of bile from the gallbladders of these animals showed that the saponifiable fraction was relatively high in the dog and sheep but low in the ox and hog. Similar analysis of human bile showed that the concentration of the saponifiable fraction was extremely low in proportion to the nonsaponifiable or cholesterol fraction. These findings, along with the previous work of Walsh and Ivy,2suggested that the fatty acids in the bile play an extremely significant role in maintaining cholesterol in solution and in preventing the

Precipitin, Lysin and Agglutinin Tests with Bile

Certain reactions of bile with toxins, blood cells, bacteria, and protein solutions simulate the antibody reactions of immune serums, and have been the object of many studies, the results of which may be briefly summarized. Antivenomous and other antitoxic properties of bile, in mixtures with the venom or toxin, are well established, but the protective value of bile injected separately is doubtful and the presence of immunologic antibodies therefore questioned. Cytolytic action on red blood cells and pneumococci, without the addition of complement, has been demonstrated for a great variety of biles. This cytolytic action, and the bacteriostatic or germicidal action demonstrated in most instances with typhoid or related organisms, have been attributed by the greater number of authors to the bile acids or salts, and to the higher unsaturated fatty acids, rather than to immune substances in the bile. These conclusions are generally based on the absence in the bile reactions of direct response to immunizing injections and of graded quantitative variations which are characteristic of serum reactions, on the inhibition by normal serums, and on the production of cytolysis and bacteriostasis with isolated acid or salt solutions. Nonspecific agglutinin for typhoid organisms and precipitin for egg white and dog serum have also been found in normal bile. Specific lysin and agglutinin have been found in the bile of immunized animals only after comparatively high titers have been attained in the serums, and perhaps more frequently are not demonstrable. Specific precipitin was not found in the one investigation reported. The detailed review of the literature follows.