Sample records for cholic acids
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Gültekin, Aytaç; Karanfil, Gamze; Sönmezoğlu, Savaş; Say, Rıdvan
2014-09-01
Determination of cholic acid is very important and necessary in body fluids due to its both pharmaceutical and clinical significance. In this study, a quartz crystal microbalance (QCM) nanosensor, which is imprinted cholic acid, has been developed for the assignation of cholic acid. The cholic acid selective memories have been generated on QCM electrode surface by using molecularly imprinted polymer (MIP) based on methacryloylamidohistidine-copper (II) (MAH-Cu(II)) pre-organized monomer. The cholic acid imprinted nanosensor was characterized by atomic force microscopy (AFM) and then analytical performance of the cholic acid imprinted QCM nanosensor was studied. The detection limit was found to be 0.0065μM with linear range of 0.01-1,000 μM. Moreover, the high value of Langmuir constant (b) (7.3*10(5)) obtained by Langmuir graph showed that the cholic acid imprinted nanosensor had quite strong binding sites affinity. At the last step of this procedure, cholic acid levels in body fluids were determined by the prepared imprinted QCM nanosensor. Copyright © 2014 Elsevier B.V. All rights reserved.
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Bile acids. XLIV, quantitation of bile acids from the bile fistula rat given (4-14C) cholesterol.
Siegfried, C M; Doisy, E A; Elliott, W H
1975-01-24
The bile acids derived from [4-14-C]cholesterol administered intracardially to rats with cannulated bile ducts were identified and quantitated. Over a period of 28 days about 90% of the administered 14-C was found in bile of which 73% was retained in the biliary acid fraction. [7beta-3-H]cholic acid, alpha-muri[3beta-3-H]cholic acid, beta-muri[3beta-3-H]cholic acid and litho[3beta-3-H]cholic acid were prepared with specific activities of about 30 muCi/mg by reduction of appropriate ketonic precursors with NaB3H4 and were added to the biliary acid fraction. After separation and purification of the bile acids, cholic, chenodeoxycholic, alpha- and beta-muricholic acids accounted for 70, 16, 7.5 and 6.1%, respectively, of the 14-C in the biliary acid fraction. The specific activities of these isolated 14-C-labeled acids were almost identical. Lithocholic acid accounted for a maximum of 0.2% and ursodeoxycholic acid and 7-oxolithocholic acid could account for no more than 2% of the biliary 14-C. Gas-liquid chromatography on 3% OV-17 of the trimethylsilyl ether derivatives of the methyl esters of the common bile acids of rat bile results in their complete separation and provides a convenient means of estimating the relative proportions of these acids in rat bile. By this method, the relative amounts of the four major acids, cholic, chenodeoxycholic, alpha- and beta-muricholic acids were 63, 20, 8 and 6%, respectively.
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Baba, M; Schols, D; Nakashima, H; Pauwels, R; Parmentier, G; Meijer, D K; De Clercq, E
1989-01-01
Several cholic acid derivatives such as taurolithocholic acid, lithocholic acid 3-sulfate, taurolithocholic acid 3-sulfate, and glycolithocholic acid 3-sulfate were shown to inhibit selectively the replication of human immunodeficiency virus type 1 (HIV-1) in vitro. These compounds completely protected MT-4 cells against HIV-1-induced cytopathogenicity at a concentration of 100 micrograms/ml, whereas no toxicity for the host cells was observed at 200 micrograms/ml. They also inhibited HIV-1 antigen expression in HIV-1-infected CEM cells. The bile acids (cholic acid, deoxycholic acid, chenodeoxycholic acid, and lithocholic acid) did not show any inhibitory effect on HIV-1 replication at concentrations that were not toxic to the host (MT-4) cells. From a structure-function analysis of a number of cholic acid derivatives, the presence of either a sulfonate (as in the tauro conjugates) or a sulfate group as well as the "litho" configuration appeared to be necessary for the expression of anti-HIV-1 activity. The active cholic acid derivatives did not directly inactivate the virus particles at the concentrations that were not toxic to the host cells. Lithocholic acid 3-sulfate, taurolithocholic acid 3-sulfate, and glycolithocholic acid 3-sulfate, but not taurolithocholic acid, partially inhibited virus adsorption to MT-4 cells. These three compounds were also inhibitory to the reverse transcriptase activity associated with HIV-1.
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Salen, G; Shefer, S; Setoguchi, T; Mosbach, E H
1975-01-01
To study the role of C25-HYDROXY BILE ALCOHOLS AS PRECURSORS OF CHOlic acid, [G-3-H]5beta-cholestane-3alpha,7alpha12alpha,25-tetrol was administered intravenously to two subjects with cerebrotendinous xanthomatosis (CTX) and two normal individuals. One day after pulse labeling, radioactivity was present in the cholic acid isolated from the bile and feces of the subjects with CTX and the bile of the normal individuals. In the two normal subjects, the sp act decay curves of [G-3-H]-cholic acid were exponential, and no traces of [G-3-H]-5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol were detected. In contrast, appreciable quantities of labeled 5beta-cholestane-3alpha,-7aopha,12alpha,25-tetrol were present in the bile and feces of the CTX subjects. The sp act vs. time curves of fecal [G-3-H]5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol and [G-3-H]-cholic acid showed a precursor-product relationship. Although these results suggest that 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol may be a precursor of cholic acid in man, the possibility that C26-hydroxy intermediates represent the normal pathway can not be excluded. PMID:1141434
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Chen, Dan-qi; Wang, Xin; Chen, Lin; He, Jin-xue; Miao, Ze-hong; Shen, Jing-kang
2011-01-01
Aim: Cytarabine is an efficient anticancer agent for acute myelogenous leukemia, but with short plasma half-life and rapid deamination to its inactive metabolite. The aim of this study was to design and synthesize novel cholic acid-cytarabine conjugates to improve its pharmacokinetic parameters. Methods: The in vitro stability of novel cholic acid-cytarabine conjugates was investigated in simulated gastric and intestinal fluid, mouse blood and liver homogenate using HPLC. The portacaval samples of the conjugates were examined in male Sprague-Dawley rats using LC/MS, and in vivo distribution was examined in male Kunming mice using LC/MS. Antitumor activities were tested in HL60 cells using MTT assay. Results: Cholic acid-cytarabine compounds with four different linkers were designed and synthesized. All the four cholic acid-cytarabine conjugates could release cytarabine when incubated with the simulated gastric and intestinal fluid, mouse blood and liver homogenate. The conjugates 6, 12, and 16 were present in the portacaval samples, whereas the conjugate 7 was not detected. The conjugates 6 and 16 showed high specificity in targeting the liver (liver target index 34.9 and 16.3, respectively) and good absorption in vivo, as compared with cytarabine. In cytarabine-sensitive HL60 cells, the conjugates 6, 12, and 16 retained potent antitumor activities. Conclusion: Three novel cholic acid-cytarabine conjugates with good liver-targeting properties and absorption were obtained. Further optimization of the conjugates is needed in the future. PMID:21516131
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Poh-Fitzpatrick, M B; Sklar, J A; Goldsman, C; Lefkowitch, J H
1983-01-01
Short-term effects of cholic acid ingestion on hepatic accumulation, fecal excretion, and blood levels of protoporphyrin were studied in vivo in griseofulvin-induced protoporphyric mice. Experimental mice that received feed with 2% griseofulvin and 0.5% cholic acid were compared with control mice that received feed with 2% griseofulvin for 4 wk. Five mice from each group were assessed each week for liver and blood porphyrin levels. Fecal protoporphyrin was compared weekly in the total pooled output of each population. Mean protoporphyrin levels were significantly lower for liver (P less than 0.0001), erythrocytes (P less than 0.05), and plasma (P less than 0.05), and higher for feces (P less than 0.001) for the mice that were fed cholic acid. Microscopic protoporphyrin deposits, inflammation, necrosis, and dysplasia were more severe in livers of control mice. A second experimental design compared four regimens in the feed given to all mice after 1-wk induction with 2% griseofulvin: (a) 0.5% cholic acid, (b) no adulterant, (c) 2% griseofulvin and 0.5% cholic acid, and (d) 2% griseofulvin. No difference in protoporphyrin removal from livers of mice in groups 1 and 2 was observed after 1 and 2 wk of these regimens. The apparent reduction in hepatic protoporphyrin content in mice of group 3 as compared with group 4 at weeks 2 and 3 was not significant at P less than 0.05. These data suggest that in selected circumstances, hepatic protoporphyrin secretion may be enhanced in protoporphyric disease states by bile salt supplementation. Images PMID:6630515
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Preparation of the 3-monosulphates of cholic acid, chenodeoxycholic acid and deoxycholic acid.
Haslewood, E S; Haslewood, G A
1976-01-01
1. The 3-sulphates of cholic, chenodeoxycholic and deoxycholic acids were prepared as crystalline disodium salts. 2. The method described shows that it is possible to prepare specific sulphate esters of polyhydroxy bile acids and to remove protecting acyl groups without removing the sulphate. 3. A study of bile acid sulphate solvolysis showed that none of the usual methods give the original bile acid in major yield in a single step. 4. An understanding of the preparation, properties and methods of solvolysis of bile acid sulphates is basic for investigations of cholestasis and liver disease. PMID:938488
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Batta, A K; Shefer, S; Salen, G
1981-05-01
Separation of the glycine and taurine conjugates of ursodeoxycholic acid from those of lithocholic acid, chenodeoxycholic acid, deoxycholic acid, and cholic acid by thin-layer chromatography is described. Thus, on running a silica gel G plate first in a solvent system of n-butanol-water 20:3 and then in a second solvent system of chloroform-isopropanol-acetic acid-water 30:20:4:1, all the above-mentioned conjugated bile acids are separated from one another. The application of this method to study the change in the biliary bile acid conjugation pattern in ursodeoxycholic acid-fed gallstone patients is described.
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Giovannini, Pier Paolo; Grandini, Alessandro; Perrone, Daniela; Pedrini, Paola; Fantin, Giancarlo; Fogagnolo, Marco
2008-12-22
We report the very efficient biotransformation of cholic acid to 7-keto- and 7,12-diketocholic acids with Acinetobacter calcoaceticus lwoffii. The enzymes responsible of the biotransformation (i.e. 7alpha- and 12alpha-hydroxysteroid dehydrogenases) are partially purified and employed in a new chemo-enzymatic synthesis of ursodeoxycholic acid starting from cholic acid. The first step is the 12alpha-HSDH-mediated total oxidation of sodium cholate followed by the Wolf-Kishner reduction of the carbonyl group to chenodeoxycholic acid. This acid is then quantitatively oxidized with 7alpha-HSDH to 7-ketochenodeoxycholic acid, that was chemically reduced to ursodeoxycholic acid (70% overall yield).
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He, Jiao; Li, Jing; Sun, Wenji; Zhang, Tianyou; Ito, Yoichiro
2012-01-01
Coupled with evaporative light scattering detection, a high-speed counter-current chromatography (HSCCC) method was developed for preparative isolation and purification of three glycine-conjugated cholic acids, glycochenodeoxycholic acid (GCDCA), glycohyodeoxycholic acid (GHDCA) and glycohyocholic acid (GHCA) from Pulvis Fellis Suis (Pig gallbladder bile) for the first time. The separation was performed with a two-phase solvent system consisted of chloroform-methanol-water-acetic acid (65:30:10:1.5, v/v/v/v) by eluting the lower phase in the head-to-tail elution mode. The revolution speed of the separation column, flow rate of the mobile phase and separation temperature were 800 rpm, 2 ml/min and 25 °C, respectively. In a single operation, 33 mg of GCDCA, 38 mg of GHDCA and 23 mg of GHCA were obtained from 200 mg of crude extract with the purity of 95.65%, 96.72% and 96.63%, respectively, in one step separation. The HSCCC fractions were analyzed by high-performance liquid chromatography (HPLC) and the structures of the three glycine-conjugated cholic acids were identified by ESI-MS, (1)H NMR and (13)C NMR.
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He, Jiao; Li, Jing; Sun, Wenji; Zhang, Tianyou; Ito, Yoichiro
2011-01-01
Coupled with evaporative light scattering detection, a high-speed counter-current chromatography (HSCCC) method was developed for preparative isolation and purification of three glycine-conjugated cholic acids, glycochenodeoxycholic acid (GCDCA), glycohyodeoxycholic acid (GHDCA) and glycohyocholic acid (GHCA) from Pulvis Fellis Suis (Pig gallbladder bile) for the first time. The separation was performed with a two-phase solvent system consisted of chloroform-methanol-water-acetic acid (65:30:10:1.5, v/v/v/v) by eluting the lower phase in the head-to-tail elution mode. The revolution speed of the separation column, flow rate of the mobile phase and separation temperature were 800 rpm, 2 ml/min and 25 °C, respectively. In a single operation, 33 mg of GCDCA, 38 mg of GHDCA and 23 mg of GHCA were obtained from 200 mg of crude extract with the purity of 95.65%, 96.72% and 96.63%, respectively, in one step separation. The HSCCC fractions were analyzed by high-performance liquid chromatography (HPLC) and the structures of the three glycine-conjugated cholic acids were identified by ESI-MS, 1H NMR and 13C NMR. PMID:23008527
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He, Xiao-Qiong; Duan, Jia-Li; Zhou, Jin; Song, Zhong-Yu; Cichello, Simon Angelo
2015-01-01
Faecal pH and cholate are two important factors that can affect colon tumorigenesis, and can be modified by diet. In this study, the effects of two Chinese traditional cooking oils (pork oil and canola/rapeseed oil) on the pH and the cholic acid content in feces, in addition to colon tumorigenesis, were studied in mice. Kunming mice were randomized into various groups; negative control group (NCG), azoxymethane control group (ACG), pork oil group (POG), and canola oil Ggroup (COG). Mice in the ACG were fed a basic rodent chow; mice in POG and COG were given 10% cooking oil rodent chow with the respective oil type. All mice were given four weekly AOM (azoxymethane) i.p. injections (10 mg/kg). The pH and cholic acid of the feces were examined every two weeks. Colon tumors, aberrant crypt foci and organ weights were examined 32 weeks following the final AOM injection. The results showed that canola oil significantly decreased faecal pH in female mice (P<0.05), but had no influence on feces pH in male mice (P>0.05). Pork oil significantly increased the feces pH in both male and female mice (P<0.05). No significant change was found in feces cholic acid content when mice were fed 10% pork oil or canola oil compared with the ACG. Although Kunming mice were not susceptible to AOM-induced tumorigenesis in terms of colon tumor incidence, pork oil significantly increased the ACF number in male mice. Canola oil showed no influence on ACF in either male or female mice. Our results indicate that cooking oil effects faecal pH, but does not affect the faecal cholic acid content and thus AOM-induced colon neoplastic ACF is modified by dietary fat.
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Preparation of radioactive iodinated cholylhistamine for use in the radioimmunoassay of cholic acid
DOE Office of Scientific and Technical Information (OSTI.GOV)
Weinberg, P.B.; Kinkade, J.M. Jr.; Collins, D.C.
1977-11-01
A major handicap in the development of simple and accurate radioimmunoassay procedures for bile acids has been the lack of a radioactive standard of high specific activity. To provide such a compound, we first synthesized cholylhistamine using the carbodiimide reaction. The hypothesized structure was confirmed by elemental analysis, thin-layer chromatography, infrared and mass spectral analysis. The cholylhistamine was then iodinated with /sup 125/I, using the choloramine-T method. The /sup 125/I-cholylhistamine was bound by antisera raised against a cholic acid-bovine serum albumin conjugate. This procedure should prove useful in preparing radioactive conjugates for all of the bile acids.
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Zhu, Yan; Li, Guodong; Williams, Jessica A.; Buckley, Kyle; Tawfik, Ossama; Luyendyk, James P.
2016-01-01
Farnesoid X receptor (FXR) belongs to the nuclear receptor superfamily with its endogenous ligands bile acids. Mice with whole body FXR deficiency develop liver tumors spontaneously, but the underlying mechanism is unclear. Moreover, it is unknown whether FXR deficiency in liver alone serves as a tumor initiator or promoter during liver carcinogenesis. This study aims to evaluate the effects of hepatocyte-specific FXR deficiency (FXRhep−/−) in liver tumor formation. The results showed that FXRhep−/− mice did not show spontaneous liver tumorigenesis with aging (up to 24 mo of age). Therefore FXRhep−/− mice were fed a bile acid (cholic acid)-containing diet alone or along with a liver tumor initiator, diethylnitrosamine (DEN). Thirty weeks later, no tumors were found in wild-type or FXRhep−/− mice without any treatment or with DEN only. However, with cholic acid, while only some wild-type mice developed tumors, all FXRhep−/− mice presented with severe liver injury and tumors. Interestingly, FXRhep−/− mouse livers increased basal expression of tumor suppressor p53 protein, apoptosis, and decreased basal cyclin D1 expression, which may prevent tumor development in FXRhep−/− mice. However, cholic acid feeding reversed these effects in FXRhep−/− mice, which is associated with an increased cyclin D1 and decreased cell cycle inhibitors. More in-depth analysis indicates that the increased in cell growth might result from disturbance of the MAPK and JAK/Stat3 signaling pathways. In conclusion, this study shows that hepatic FXR deficiency may only serve as a tumor initiator, and increased bile acids is required for tumor formation likely by promoting cell proliferation. PMID:26744468
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Galatola, G.; Jazrawi, R.P.; Bridges, C.
/sup 75/Se-homocholic acid-taurine (/sup 75/SeHCAT) is the first available gamma-labeled bile acid, and should therefore be handled more efficiently and specifically by the liver than previous hepatoscintigraphic agents. We have measured serum and hepatic kinetics for /sup 75/SeHCAT, and compared them with those for the conventional hepatobiliary scintigraphic agent 99mTc-hepatoiminodiacetic acid, and with serum kinetics for the corresponding natural bile acid, (/sup 14/C)cholic acid-taurine. We used a dynamic scintigraphic technique and serial blood sampling in 8 subjects. Initial hepatic uptake rate was identical to initial serum disappearance rate (14% dose/min) for /sup 75/SeHCAT, but significantly lower for 99mTc-hepatoiminodiacetic acid (6%more » vs. 14% dose/min, p less than 0.001). Hepatic transit time was shorter for /sup 75/SeHCAT (13 min vs. 22 min, p less than 0.02), net hepatic excretory rate was more rapid (1.4% vs. 0.8% dose/min, p less than 0.001), and urinary excretion was lower (1.0% vs. 9.0% dose, p less than 0.001). Initial and late-plasma disappearance rates were significantly lower for /sup 75/SeHCAT (14.3% and 1.5% dose/min) than for (/sup 14/C)cholic acid-taurine (21.3% and 2.8% dose/min, respectively), and plasma clearance was also lower (2/sup 75/ vs. 670 ml/min). In vitro, /sup 75/SeHCAT was bound to serum proteins more completely than (/sup 14/C)cholic acid-taurine (90.4% vs. 86.5%, p less than 0.005). We conclude that /sup 75/SeHCAT provides a hepatoscintigraphic agent that is handled more efficiently and specifically by the liver than the conventionally used agent 99mTc-hepatoiminodiacetic acid. It is not cleared from the serum as rapidly as (/sup 14/C)cholic acid-taurine, probably due to its stronger protein binding. The clinical value of /sup 75/SeHCAT in assessing liver disease should be investigated.« less
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He, Jiao; Zhang, Yongmin; Ito, Yoichiro; Sun, Wenji
2011-01-01
Coupled with evaporative light scattering detection, a high-speed counter-current chromatography (HSCCC) method was applied to the separation and purification of three tauro-conjugated cholic acids of taurochenodeoxycholic acid (TCDCA), taurohyodeoxycholic acid (THDCA) and taurohyocholic acid (THCA) from Pulvis Fellis Suis (Pig gallbladder bile) for the first time. The two-phase solvent system composed of chloroform-methanol-water-acetic acid (4:4:2:0.3, v/v/v/v) was selected for the one-step separation where the lower phase was used as the mobile phase in the head to tail elution mode. The revolution speed of the separation column, flow rate of the mobile phase and separation temperature were 800 rpm, 1.5 ml/min and 25°C respectively. From 100 mg of the crude extract, 10.2 mg of TCDCA, 11.8 mg of THDCA and 5.3 mg of THCA were obtained with the purity of 94.6%, 96.5% and 95.4%, respectively. in one step separation The HSCCC fractions were analyzed by high-performance liquid chromatography (HPLC) and the structures of the three tauro-conjugated cholic acids were identified by ESI-MS, (1)H NMR and (13)C NMR.
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[Combined action of nitrofuran preparations and bile acids on staphylococci].
Tkachuk, N I
1984-03-01
The effect of cholic, glycocholic and deoxycholic bile acids on the antimicrobial activity of furacin, furadonin, furagin and furoxone was studied with the use of collection strains and fresh isolates of staphylococci. The method of dilutions in liquid media was used. Cholic and glycocholic acids lowered the MIC of furacin, furadonin, furoxone and furagin with respect to the collection strains by 4-16, 5, 4-6 and 22-37 times, respectively. The potentiating effect of deoxycholic acid on the nitrofuran drugs was even more pronounced. Thus, when the nitrofurans were used in combination with deoxycholic acid, their MIC dropped by 16-114 times. A significant increase in the antimicrobial activity of the nitrofurans under the effect of the bile acids was also observed with respect to the fresh isolates of Staphylococcus, while it was somewhat lower. The subbacteriostatic doses of cholic, glycocholic and deoxycholic bile acids also increased the bactericidal effect of the nitrofuran drugs. The minimum bactericidal concentrations (MBC) of furacin, furoxone, furadonin and furagin decreased from 12.5, 2.08, 25.0 and 1.82 to 0.78, 0.26, 2.34 and 0.032 micrograms/ml, respectively. The most pronounced decrease in the MBC was observed under the effect of deoxycholic acid. Therefore, the bile acids potentiated the nitrofuran antistaphylococcal activity. The combinations of deoxycholic acid with furagin or furoxone were the most effective.
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Merrick, M V; Eastwood, M A; Anderson, J R; Ross, H M
1982-02-01
A conjugated bile acid, 23-selena-25-homotaurocholic acid (SeHCAT), labeled with the gamma emitter Se-75, has been evaluated in man. Absorption and excretion were compared with that of simultaneously administered [23-14C]cholic acid. SeHCAT is absorbed quantitatively following oral administration, secreted into the bile at the same rate as cholic acid, reabsorbed from the small intestine, and resecreted. It is not absorbed when the terminal ileum has been excised or bypassed. SeHCAT is therefore the first of a new class of radiopharmaceuticals, namely, gamma-emitting tracers of the complete cycle of the enterohepatic circulation. Its use will simplify investigation of the functional state of the terminal ileum by eliminating the need to collect and process feces.
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Hu, Meng-Xin; Li, Xiang; Li, Ji-Nian; Huang, Jing-Jing; Ren, Ge-Rui
2018-02-23
Polymer brushes modified surfaces have been widely used for protein immobilization and isolation. Modification of membranes with polymer brushes increases the surface concentration of affinity ligands used for protein binding. Albumin is one of the transporting proteins and shows a high affinity to bile acids. In this work, the modified membranes with cholic acid-containing polymer brushes can be facilely prepared by the immobilization of cholic acid on the poly(2-hydroxyethyl methacrylate) grafted microporous polypropylene membranes (MPPMs) for affinity adsorption of albumin. ATR/FT-IR and X-ray photoelectron spectroscopy were used to characterize the chemical composition of the modified membranes. Water contact angle measurements were used to analyze the hydrophilic/hydrophobic properties of the membrane surface. The modified MPPMs show a high affinity to albumin and have little non-specific adsorption of hemoglobin. The dynamic binding capacity of albumin in the continous-flow system increases with the cycle number and feed rate as the binding degree of cholic acid is moderate. The highest binding capacity of affinity membranes is about 52.49 g/m 2 membrane, which is about 24 times more than the monolayer binding capacity. These results reveal proteins could be captured in multilayers by the polymer brushes containing affinity ligands similar to the polymer brushes containing ion-exchange groups, which open up the potential of the polymer brushes containing affinity ligands in protein or another components separation. And the cholic acid containing polymer brushes modified membranes has the promising potential for albumin separation and purification rapidly from serum or fermented solution in medical diagnosis and bioseparation. Copyright © 2018 Elsevier B.V. All rights reserved.
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Transporter-targeted cholic acid-cytarabine conjugates for improved oral absorption.
Zhang, Dong; Li, Dongpo; Shang, Lei; He, Zhonggui; Sun, Jin
2016-09-10
Cytarabine has a poor oral absorption due to its rapid deamination and poor membrane permeability. Bile acid transporters are highly expressed both in enterocytes and hepatocytes and to increase the oral bioavailability and investigate the potential application of cytarabine for liver cancers, a transporter- recognizing prodrug strategy was applied to design and synthesize four conjugates of cytarabine with cholic acid (CA), chenodeoxycholic acid (CDCA), hyodeoxycholic acid (HDCA) and ursodeoxycholic acid (UDCA). The anticancer activities against HepG2 cells were evaluated by MTT assay and the role of bile acid transporters during cellular transport was investigated in a competitive inhibition experiment. The in vitro and in vivo metabolic stabilities of these conjugates were studied in rat plasma and liver homogenates. Finally, an oral bioavailability study was conducted in rats. All the cholic acid-cytarabine conjugates (40μM) showed potent antiproliferative activities (up to 70%) against HepG2 cells after incubation for 48h. The addition of bile acids could markedly reduce the antitumor activities of these conjugates. The N(4)-ursodeoxycholic acid conjugate of cytarabine (compound 5) exhibited optimal stability (t1/2=90min) in vitro and a 3.9-fold prolonged half-life of cytarabine in vivo. More importantly, compound 5 increased the oral bioavailability 2-fold compared with cytarabine. The results of the present study suggest that the prodrug strategy based on the bile acid transporters is suitable for improving the oral absorption and the clinical application of cytarabine. Copyright © 2016 Elsevier B.V. All rights reserved.
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Jia, Yong-Guang; Zhu, X X
2015-11-11
A family of block and random copolymers of norbornene derivatives bearing cholic acid and oligo(ethylene glycol) pendants were prepared in the presence of Grubbs' catalyst. The phase transition temperature of the copolymers in aqueous solutions may be tuned by the variation of comonomer ratios and pH values. Both types of copolymers formed micellar nanostructures with a hydrophilic poly(ethylene glycol) shell and a hydrophobic core containing cholic acid residues. The micellar size increased gradually with increasing pH due to the deprotonation of the carboxylic acid groups. These micelles were capable of encapsulating hydrophobic compounds such as Nile Red (NR). A higher hydrophobicity/hydrophilicity ratio in both copolymers resulted in a higher loading capacity for NR. With similar molecular weights and monomer compositions, the block copolymers showed a higher loading capacity for NR than the random copolymers. The NR-loaded micelles exhibited a pH-triggered release behavior. At pH 7.4 within 96 h, the micelles formed by the block and random of copolymers released 56 and 97% NR, respectively. Therefore, these micelles may have promise for use as therapeutic nanocarriers in drug delivery systems.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Merrick, M.V.; Eastwood, M.A.; Anderson, J.R.
A conjugated bile acid, 23-selena-25-homotaurocholic acid (SeHCAT), labeled with the gamma emitter Se-75, has been evaluated in man. Absorption and excretion were compared with that of simultaneously administered (23-14C)cholic acid. SeHCAT is absorbed quantitatively following oral administration, secreted into the bile at the same rate as cholic acid, reabsorbed from the small intestine, and resecreted. It is not absorbed when the terminal ileum has been excised or bypassed. SeHCAT is therefore the first of a new class of radiopharmaceuticals, namely, gamma-emitting tracers of the complete cycle of the enterohepatic circulation. Its use will simplify investigation of the functional state ofmore » the terminal ileum by eliminating the need to collect and process feces.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Merrick, M.V.; Eastwood, M.A.; Anderson, J.R.
A conjugated bile acid, 23-selena-25-homotaurocholic acid (SeHCAT), labeled with the gamma emitter Se-75, has been evaluated in man. Absorption and excretion were compared with that of simultaneously administered (23-/sup 14/C)cholic acid. SeHCAT is absorbed quantitatively following oral administration, secreted into the bile at the same rate as cholic acid, reabsorbed from the small intestine, and resecreted. It is not absorbed when the terminal ileum has been excised or bypassed. SeHCAT is therefore the first of a new class of radiopharmaceuticals, namely, gamma-emitting tracers of the complete cycle of the enterohepatic circulation. Its use will simplify investigation of the functional statemore » of the terminal ileum by eliminating the need to collect and process feces.« less
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Optical biosensor based on liquid crystal droplets for detection of cholic acid
NASA Astrophysics Data System (ADS)
Niu, Xiaofang; Luo, Dan; Chen, Rui; Wang, Fei; Sun, Xiaowei; Dai, Haitao
2016-12-01
A highly sensitive cholic acid biosensor based on 4-cyano-4‧-penthlbiphenyl (5CB) Liquid crystal droplets in phosphate buffer saline solution was reported. A radial-to-bipolar transition of 5CB droplet would be triggered during competitive reaction of CA at the sodium dodecyl sulfate surfactant-laden 5CB droplet surface. Our liquid crystal droplet sensor is a low-cost, simple and fast method for CA detection. The detection limit (5 μM) of our method is 2.4 times lower than previously report by using liquid crystal film to detection of CA.
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Schacht, Anna Christina; Sørensen, Michael; Munk, Ole Lajord; Frisch, Kim
2016-04-01
During cholestasis, accumulation of conjugated bile acids may occur in the liver and lead to hepatocellular damage. Inspired by our recent development of N-(11)C-methyl-glycocholic acid-that is, (11)C-cholylsarcosine-a tracer for PET of the endogenous glycine conjugate of cholic acid, we report here a radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids and biodistribution studies in pigs by PET/CT. A radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids was developed and used to prepare N-(11)C-methyl-taurine conjugates derived from cholic, chenodeoxycholic, deoxycholic, ursodeoxycholic, and lithocholic acid. The lipophilicity of these new tracers was determined by reversed-phase thin-layer chromatography. The effect of lipophilicity and structure on the biodistribution was investigated in pigs by PET/CT using the tracers derived from cholic acid (3α-OH, 7α-OH, 12α-OH), ursodeoxycholic acid (3α-OH, 7β-OH), and lithocholic acid (3α-OH). The radiosyntheses of the N-(11)C-methyl-taurine-conjugated bile acids proceeded with radiochemical yields of 61% (decay-corrected) or greater and radiochemical purities greater than 99%. PET/CT in pigs revealed that the tracers were rapidly taken up by the liver and secreted into bile. There was no detectable radioactivity in urine. Significant reflux of N-(11)C-methyl-taurolithocholic acid into the stomach was observed. We have successfully developed a radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids. These tracers behave in a manner similar to endogenous taurine-conjugated bile acids in vivo and are thus promising for functional PET of patients with cholestatic diseases. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
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Cheng, Ye; Cai, Huanxin; Yin, Baoru; Yao, Ping
2013-09-15
A series of novel amphiphilic chitosan derivatives, cholic acid modified N-(2-hydroxy)-propyl-3-trimethylammonium chitosan chloride (HTCC-CA) with different quaternization degrees and cholic acid substitutions were synthesized in this study. HTCC-CA is biocompatible and forms particles in aqueous solution. The binding with superoxide dismutase (SOD) at pH 6.8 destroys the original aggregates of HTCC-CA and produces smaller SOD/HTCC-CA complex nanoparticles via electrostatic and hydrophobic interactions. The SOD loading efficiency and loading capacity of HTCC-CA can reach to more than 90% and 45%, respectively. Confocal laser scanning microscopy observation and flow cytometry analysis reveal that SOD/HTCC-CA complex nanoparticles greatly enhance the cellular internalization of the loaded SOD. The SOD activities and malonaldehyde concentrations in the serum and organs of the rats, administrated intravenously with free SOD, free HTCC-CA, and SOD/HTCC-CA nanoparticles, were assayed to evaluate the antioxidant efficiency in vivo. The results demonstrate that free HTCC-CA is effective to scavenge superoxide radicals in the blood circulation and SOD/HTCC-CA nanoparticles have better antioxidant efficiency than free SOD as well as free HTCC-CA. Copyright © 2013 Elsevier B.V. All rights reserved.
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Kołodziejczyk, Michał Krzysztof; Nachajski, Michal Jakub; Lukosek, Marek; Zgoda, Marian Mikołaj
2013-01-01
Solubilizing properties of aqueous solutions of a series of surface-active agents, products of oxyethylation of cholic acid, were examined in the present study. The content of oxyethylated segments determined by means of the 1H NMR method enabled the verification of the molecular mass of surfactants along with the calculation of the structural hydrophilic-lipophilic balance (HLB), the solubility parameter delta1/2, and the required solubility level of balance HLB(R). Viscosimetric measurements enabled the calculation of the limiting viscosity number, the content-average molecular mass, the effective volume, the hydrodynamic radius of the surfactant micelle and their equilibrium adducts with rutin, diclofenac and loratadine (BCS Class II and III). By means of the spectrophotometric method (UV) the amount of the solubilized diclofenac, loratadine and rutin (rutoside) was determined in the equilibrium system (saturated solution) in the environment of aqueous solutions of cholic acid derivatives of n(TE) = 20-70. The obtained results serve as a basis for determining the solubilization mechanism of lipophilic therapeutic products and indirectly for estimating the influence of the above process on pharmaceutical as well as biological availability of a micellar adduct from model drug forms (Lindbladt lithogenolitic index).
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Boyd, G.S.; Merrick, M.V.; Monks, R.
Four selenium-labeled free bile acids and four selenium-labeled conjugated bile acids, labeled with Se-75 at the C-19, C-22, C-23, or C-24 position, have been synthesized and their absorption and excretion compared with that of (24-/sup 14/C)cholic acid, following both oral and intravenous administration. All but one of the compounds is absorbed and excreted in bile to a significant extent. One compound, SeHCAT, has been selected for particular study. It is quantitatively absorbed from the gut at the same rate as cholic acid, and both are excreted into the bile at the same rate. It remains almost entirely confined to themore » enterohepatic circulation (the gut, liver, and biliary tree) and excretion is exclusively fecal. Such a compound offers the possibility of a simple, novel, and aesthetically acceptalbe method investigating small-bowel disease.« less
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Suga, Takahiro; Sato, Toshihiro; Maekawa, Masamitsu; Goto, Junichi; Mano, Nariyasu
2017-01-01
Bile acids, the metabolites of cholesterol, are signaling molecules that play critical role in many physiological functions. They undergo enterohepatic circulation through various transporters expressed in intestine and liver. Human organic anion-transporting polypeptides (OATP) 1B1 and OATP1B3 contribute to hepatic uptake of bile acids such as taurocholic acid. However, the transport properties of individual bile acids are not well understood. Therefore, we selected HEK293 cells overexpressing OATP1B1 and OATP1B3 to evaluate the transport of five major human bile acids (cholic acid, chenodeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, lithocholic acid) together withtheir glycine and taurine conjugates via OATP1B1 and OATP1B3. The bile acids were quantified by liquid chromatography-tandem mass spectrometry. The present study revealed that cholic acid, chenodeoxyxcholic acid, and deoxycholic acid were transported by OATP1B1 and OATP1B3, while ursodeoxycholic acid and lithocholic acid were not significantly transported by OATPs. However, all the conjugated bile acids were taken up rapidly by OATP1B1 and OATP1B3. Kinetic analyses revealed the involvement of saturable OATP1B1- and OATP1B3-mediated transport of bile acids. The apparent Km values for OATP1B1 and OATP1B3 of the conjugated bile acids were similar (0.74–14.7 μM for OATP1B1 and 0.47–15.3 μM for OATP1B3). They exhibited higher affinity than cholic acid (47.1 μM for OATP1B1 and 42.2 μM for OATP1B3). Our results suggest that conjugated bile acids (glycine and taurine) are preferred to unconjugated bile acids as substrates for OATP1B1 and OATP1B3. PMID:28060902
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Hassan, Amir; Ahmed, Mansoor; Rasheed, Munawwer; Mansoor, Najia; Khan, Rafeeq Alam; Kamal, Mustafa; Rashid, Mohammad Abdur
2015-07-01
Bile from gallbladders of Arius platystomus (Singhara), Arius tenuispinis (Khagga), Pomadasys commersonni (Holoola) and Kishinoella tonggol (Dawan) were derivatised and analysed by GC-MS for identification of bile acids and bile alcohols. Cholic acid and Chenodeoxycholic acid were found as major bile acids in Arius platystomus, Arius tenuispinis and Pomadasys commersonni. Other bile acids identified in Arius platystomus were allochenodeoxycholic acid, allodeoxycholic acid, 3α,7α,12α-trihydroxy-24-methyl-5β-cholestane-26-oic acid, and 3α,7α,12α, 24-tetrahydroxy-5α-cholestane-26-oic acid. Cholesterol was found as major bile alcohol in Arius platystomus, Arius tenuispinis and Pomadasys commersonni. Cholic acid was the major bile acid identified in the bile of Kishinoella tonggol while other bile acids included 3α,7α,12α-tridydroxy-5α-cholestanoic acid and 3α,7α,12α-tridydroxy-5β-cholestanoic acid. Bile alcohol 5β-cyprinol was present in significant amounts with 5β-cholestane-3α,7α,12α,24-tetrol being the other contributors in the bile of Kishinoella tonggol.
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Bile Acid Responses in Methane and Non-Methane Producers to Standard Breakfast Meals
USDA-ARS?s Scientific Manuscript database
Bile acids and their conjugates are important regulators of glucose homeostasis. Previous research has revealed the ratio of cholic acid to deoxycholic acid to affect insulin resistance in humans. Bile acid de-conjugation and intestinal metabolism depend on gut microbes which may be affected by hos...
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NASA Astrophysics Data System (ADS)
Tang, Xiaolong; Cai, Shuyu; Zhang, Rongbo; Liu, Peng; Chen, Hongbo; Zheng, Yi; Sun, Leilei
2013-10-01
A system of novel nanoparticles of star-shaped cholic acid-core polylactide- d-α-tocopheryl polyethylene glycol 1000 succinate (CA-PLA-TPGS) block copolymer was developed for paclitaxel delivery for breast cancer treatment, which demonstrated superior in vitro and in vivo performance in comparison with paclitaxel-loaded poly( d, l-lactide- co-glycolide) (PLGA) nanoparticles and linear PLA-TPGS nanoparticles. The paclitaxel- or couramin 6-loaded nanoparticles were fabricated by a modified nanoprecipitation method and then characterized in terms of size, surface charge, surface morphology, drug encapsulation efficiency, and in vitro drug release. The CA-PLA-TPGS nanoparticles were found to be spherical in shape with an average size of around 120 nm. The nanoparticles were found to be stable, showing no change in the particle size and surface charge during 90-day storage of the aqueous solution. The release profiles of the paclitaxel-loaded nanoparticles exhibited typically biphasic release patterns. The results also showed that the CA-PLA-TPGS nanoparticles have higher antitumor efficacy than the PLA-TPGS nanoparticles and PLGA nanoparticles in vitro and in vivo. In conclusion, such nanoparticles of star-shaped cholic acid-core PLA-TPGS block copolymer could be considered as a potentially promising and effective strategy for breast cancer treatment.
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Korou, Laskarina-Maria; Agrogiannis, George; Koros, Christos; Kitraki, Efthimia; Vlachos, Ioannis S.; Tzanetakou, Irene; Karatzas, Theodore; Pergialiotis, Vasilios; Dimitroulis, Dimitrios; Perrea, Despina N.
2014-01-01
Hyperlipidemia and stress are important factors affecting cardiovascular health in middle-aged individuals. We investigated the effects of N-acetylcysteine (NAC) and sesame oil on the lipidemic status, liver architecture and the hypothalamic-pituitary-adrenal (HPA) axis of middle-aged mice fed a cholesterol-enriched diet. We randomized 36 middle-aged C57bl/6 mice into 6 groups: a control group, a cholesterol/cholic acid diet group, a cholesterol/cholic acid diet group with NAC supplementation, a cholesterol/cholic acid diet enriched with 10% sesame oil and two groups receiving a control diet enriched with NAC or sesame oil. NAC administration prevented the onset of the disturbed lipid profile, exhibiting decreased lipid peroxidation and alkaline phosphatase (ALP) levels, restored nitric oxide bioavailability and reduced hepatic damage, compared to non-supplemented groups. High-cholesterol feeding resulted in increased hypothalamic glucocorticoid receptors (GR) levels, while NAC supplementation prevented this effect. NAC supplementation presented significant antioxidant capacity by means of preventing serum lipid status alterations, hepatic damage, and HPA axis disturbance due to high-cholesterol feeding in middle-aged mice. These findings suggest a beneficial preventive action of plant-derived antioxidants, such as NAC, on lipid metabolism and on the HPA axis. PMID:25348324
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Qiao, Xue; Ye, Min; Pan, De-lin; Miao, Wen-juan; Xiang, Cheng; Han, Jian; Guo, De-an
2011-01-07
Animal biles and gallstones are popularly used in traditional Chinese medicines, and bile acids are their major bioactive constituents. Some of these medicines, like cow-bezoar, are very expensive, and may be adulterated or even replaced by less expensive but similar species. Due to poor ultraviolet absorbance and structural similarity of bile acids, effective technology for species differentiation and quality control of bile-based Chinese medicines is still lacking. In this study, a rapid and reliable method was established for the simultaneous qualitative and quantitative analysis of 18 bile acids, including 6 free steroids (cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid, hyodeoxycholic acid, and ursodeoxycholic acid) and their corresponding glycine conjugates and taurine conjugates, by using liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). This method was used to analyze six bile-based Chinese medicines: bear bile, cattle bile, pig bile, snake bile, cow-bezoar, and artificial cow-bezoar. Samples were separated on an Atlantis dC₁₈ column and were eluted with methanol-acetonitrile-water containing ammonium acetate. The mass spectrometer was monitored in the negative electrospray ionization mode. Total ion currents of the samples were compared for species differentiation, and the contents of bile acids were determined by monitoring specific ion pairs in a selected reaction monitoring program. All 18 bile acids showed good linearity (r² > 0.993) in a wide dynamic range of up to 2000-fold, using dehydrocholic acid as the internal standard. Different animal biles could be explicitly distinguished by their major characteristic bile acids: tauroursodeoxycholic acid and taurochenodeoxycholic acid for bear bile, glycocholic acid, cholic acid and taurocholic acid for cattle bile, glycohyodeoxycholic acid and glycochenodeoxycholic acid for pig bile, and taurocholic acid for snake bile. Furthermore, cattle bile, cow-bezoar, and artificial cow-bezoar could be differentiated by the existence of hyodeoxycholic acid and the ratio of cholic acid to deoxycholic acid. This study provided bile acid profiles of bile-based Chinese medicines for the first time, which could be used for their quality control. Copyright © 2010 Elsevier B.V. All rights reserved.
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Capaldi, Stefano; Guariento, Mara; Perduca, Massimiliano; Di Pietro, Santiago M; Santomé, José A; Monaco, Hugo L
2006-07-01
The family of the liver bile acid-binding proteins (L-BABPs), formerly called liver basic fatty acid-binding proteins (Lb-FABPs) shares fold and sequence similarity with the paralogous liver fatty acid-binding proteins (L-FABPs) but has a different stoichiometry and specificity of ligand binding. This article describes the first X-ray structure of a member of the L-BABP family, axolotl (Ambystoma mexicanum) L-BABP, bound to two different ligands: cholic and oleic acid. The protein binds one molecule of oleic acid in a position that is significantly different from that of either of the two molecules that bind to rat liver FABP. The stoichiometry of binding of cholate is of two ligands per protein molecule, as observed in chicken L-BABP. The cholate molecule that binds buried most deeply into the internal cavity overlaps well with the analogous bound to chicken L-BABP, whereas the second molecule, which interacts with the first only through hydrophobic contacts, is more external and exposed to the solvent. (c) 2006 Wiley-Liss, Inc.
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Usha, V; Vijayammal, P L; Kurup, P A
1989-05-01
Effect of feeding isolated dietary fiber from M. paradisiaca on the metabolism of carbohydrates in the liver has been studied. Fiber fed rats showed significantly lower levels of fasting blood glucose and higher concentration of liver glycogen. Activity of glycogen phosphorylase, glucose-1-phosphate, uridyl transferase and glycogen synthase was significantly higher while phosphoglucomutase activity showed lower activity. Activity of some glycolytic enzymes, viz. hexokinase and pyruvic kinase was lower. Glucose-6-phosphatase showed higher activity while fructose 1-6 diphosphatase activity was not affected. Glucose-6-phosphate dehydrogenase on the other hand showed higher activity. The changes in these enzyme activities have been attributed due to the effect of higher concentration of bile acids produced in the liver as a result of feeding fiber. Evidence for this has been obtained by studying the in vitro effect of cholic acid and chenodeoxy cholic acid.
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Cunningham, Alexander J; Robinson, Mattieu; Banquy, Xavier; Leblond, Jeanne; Zhu, X X
2018-03-05
Doxorubicin (Dox) is a drug of choice in the design of drug delivery systems directed toward breast cancers, but is often limited by loading and control over its release from polymer micelles. Bile acid-based block copolymers present certain advantages over traditional polymer-based systems for drug delivery purposes, since they can enable a higher drug loading via the formation of a reservoir through their aggregation process. In this study, hydrophobic and electrostatic interactions are compared for their influence on Dox loading inside cholic acid based block copolymers. Poly(allyl glycidyl ether) (PAGE) and poly(ethylene glycol) (PEG) were grafted from the cholic acid (CA) core yielding a star-shaped block copolymer with 4 arms (CA-(PAGE- b-PEG) 4 ) and then loaded with Dox via a nanoprecipitation technique. A high Dox loading of 14 wt % was achieved via electrostatic as opposed to hydrophobic interactions with or without oleic acid as a cosurfactant. The electrostatic interactions confer a pH responsiveness to the system. 50% of the loaded Dox was released at pH 5 in comparison to 12% at pH 7.4. The nanoparticles with Dox loaded via hydrophobic interactions did not show such a pH responsiveness. The systems with Dox loaded via electrostatic interactions showed the lowest IC 50 and highest cellular internalization, indicating the pre-eminence of this interaction in Dox loading. The blank formulations are biocompatible and did not show cytotoxicity up to 0.17 mg/mL. The new functionalized star block copolymers based on cholic acid show great potential as drug delivery carriers.
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Dobson, Tresha E; Maxwell, Anderson R; Ramsubhag, Adesh
2018-07-01
Six cholic acid derivatives (1-6) were isolated from broth cultures of Bacillus amyloliquefaciens UWI-W23, an isolate from the Trinidad Pitch Lake. The compounds were extracted via solvent extraction and/or XAD resin adsorption and purified using silica gel column chromatography. Their structures were elucidated using 1D, 2D NMR and ESI-MS spectrometry and FT-IR spectrophotometry. One of the compounds, taurodeoxycholate (2) is for the first time being reported from a bacterial source while deoxycholate (4) is for the first time being reported from a Gram-positive bacterium. The other compounds have not been previously isolated from Bacillus spp. viz. cholate (1), taurocholic acid (3); glycodeoxycholic acid (5) and glycocholic acid (6). All six compounds exhibited antimicrobial activity against P. aeruginosa and B. cereus with MICs ranging from 7 to 250 µg/mL. Cholate (1) also showed activity against MRSA (MICs = 125 µg/mL) and glycocholic acid (6) against S. cerevisiae (MICs = 15.6 µg/mL). Copyright © 2018 Elsevier Inc. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Boyd, G.S.; Merrick, M.V.; Monks, R.
Four selenium-labeled free bile acids and four selenium-labeled conjugated bile acids, labeled with Se-75 at the C-19, C-22, C-23, or C-24 position, have been synthesized and their absorption and excretion compared with that of (24-14C)cholic acid, following both oral and intravenous administration. All but one of the compounds is absorbed and excreted in bile to a significant extent. One compound, SeHCAT, has been selected for particular study. It is quantitatively absorbed from the gut at the same rate as cholic acid, and both are excreted into the bile at the same rate. It remains almost entirely confined to the enterohepaticmore » circulation (the gut, liver, and biliary tree) and excretion is exclusively fecal. Whole-body retention, measured for 41 days, and tissue distributions suggest that the absorbed radiation dose would be small compared with that in many established tests. Such a compound offers the possibility of a simple, novel, and aesthetically acceptable method of investigating small-bowel disease. It therefore merits further investigation.« less
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Nishimaki-Mogami, T; Takahashi, A; Toyoda, K; Hayashi, Y
1993-01-01
The capability of (4R)-4-(2,3,4,6,6a beta,7,8,9,9a alpha,9b beta-decahydro-6a beta-methyl-3-oxo-1H-cyclopental[f]quinolin-7 beta-yl)valeric acid (DCQVA), a catabolite of cholic acid produced by enterobacteria, to induce peroxisome proliferation in vivo and in vitro was studied. Rats given 0.3% DCQVA in the diet for 2 weeks showed marked increases in peroxisomal beta-oxidation, mitochondrial 2,4-dienoyl-CoA reductase and microsomal laurate omega-oxidation activities in the liver compared with control rats given the diet without DCQVA. Cultured rat hepatocytes treated with DCQVA for 72 h also exhibited greatly enhanced beta-oxidation activity. The increased activity was concentration-dependent and the effective concentrations were comparable with those of clofibric acid that produced the same degree of induction in the assay. The results demonstrate that DCQVA is a potent peroxisome proliferator that occurs naturally in rat intestine. PMID:8216219
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Du, Hongliang; Yang, Xiaoye; Pang, Xin; Zhai, Guangxi
2014-10-13
O-carboxymethyl chitosan (OCMC) was firstly decorated with cholic acid (CA) to acquire an amphiphilic polymer under alkaline condition. Then glycyrrhetinic acid (GA) was conjugated to the polymer via a succinate linker and finally treated with NaCO3 solution to obtain new conjugates for potential liver targeted delivery. These conjugates formed uniform aggregates with low critical aggregation concentrations (0.028-0.079 mg/mL) in PBS. The average diameter of cholic acid modified carboxymethyl chitosan (CMCA) aggregates (110-257 nm) decreased with the increase of CA substitution degree and became slightly larger after GA modification. Negative zeta potential (-15 mV) of GA decorated CMCA (GA-CMCA) revealed that the formation of negatively charged shells and spherical morphology was observed under transmission electron microscopy. Furthermore, hemolysis test, in vitro cytotoxicity assay and cellular uptake study all demonstrated the safety and feasibility of these conjugates as a promising carrier for liver targeted drug delivery. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Cholic acid accumulation and its diminution by short-chain fatty acids in bifidobacteria.
Kurdi, Peter; Tanaka, Hiroshi; Van Veen, Hendrik W; Asano, Kozo; Tomita, Fusao; Yokota, Atsushi
2003-08-01
Cholic acid (CA) transport was investigated in nine intestinal Bifidobacterium strains. Upon energization with glucose, all of the bifidobacteria accumulated CA. The driving force behind CA accumulation was found to be the transmembrane proton gradient (Delta pH, alkaline interior). The levels of accumulated CA generally coincided with the theoretical values, which were calculated by the Henderson-Hasselbalch equation using the measured internal pH values of the bifidobacteria, and a pK(a) value of 6.4 for CA. These results suggest that the mechanism of CA accumulation is based on the diffusion of a hydrophobic weak acid across the bacterial cell membrane, and its dissociation according to the Delta pH value. A mixture of short-chain fatty acids (acetate, propionate and butyrate) at the appropriate colonic concentration (117 mM in total) reduced CA accumulation in Bifidobacterium breve JCM 1192(T). These short-chain fatty acids, which are weak acids, reduced the Delta pH, thereby decreasing CA accumulation in a dose-dependent manner. The bifidobacteria did not alter or modify the CA molecule. The probiotic potential of CA accumulation in vivo is discussed in relation to human bile acid metabolism.
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Agarwal, Devesh S; Anantaraju, Hasitha Shilpa; Sriram, Dharmarajan; Yogeeswari, Perumal; Nanjegowda, Shankara H; Mallu, P; Sakhuja, Rajeev
2016-03-01
A series of bile acid (Cholic acid and Deoxycholic acid) aryl/heteroaryl amides linked via α-amino acid were synthesized and tested against 3 human cancer cell-lines (HT29, MDAMB231, U87MG) and 1 human normal cell line (HEK293T). Some of the conjugates showed promising results to be new anticancer agents with good in vitro results. More specifically, Cholic acid derivatives 6a (1.35 μM), 6c (1.41 μM) and 6m (4.52 μM) possessing phenyl, benzothiazole and 4-methylphenyl groups showed fairly good activity against the breast cancer cell line with respect to Cisplatin (7.21 μM) and comparable with respect to Doxorubicin (1 μM), while 6e (2.49μM), 6i (2.46 μM) and 6m (1.62 μM) showed better activity against glioblastoma cancer cell line with respect to both Cisplatin (2.60 μM) and Doxorubicin (3.78 μM) drugs used as standards. Greater than 65% of the compounds were found to be safer on human normal cell line. Copyright © 2016 Elsevier Inc. All rights reserved.
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Enzymatic routes for the synthesis of ursodeoxycholic acid.
Eggert, Thorsten; Bakonyi, Daniel; Hummel, Werner
2014-12-10
Ursodeoxycholic acid, a secondary bile acid, is used as a drug for the treatment of various liver diseases, the optimal dose comprises the range of 8-10mg/kg/day. For industrial syntheses, the structural complexity of this bile acid requires the use of an appropriate starting material as well as the application of regio- and enantio-selective enzymes for its derivatization. Most strategies for the synthesis start from cholic acid or chenodeoxycholic acid. The latter requires the conversion of the hydroxyl group at C-7 from α- into β-position in order to obtain ursodeoxycholic acid. Cholic acid on the other hand does not only require the same epimerization reaction at C-7 but the removal of the hydroxyl group at C-12 as well. There are several bacterial regio- and enantio-selective hydroxysteroid dehydrogenases (HSDHs) to carry out the desired reactions, for example 7α-HSDHs from strains of Clostridium, Bacteroides or Xanthomonas, 7β-HSDHs from Clostridium, Collinsella, or Ruminococcus, or 12α-HSDH from Clostridium or from Eggerthella. However, all these bioconversion reactions need additional steps for the regeneration of the coenzymes. Selected multi-step reaction systems for the synthesis of ursodeoxycholic acid are presented in this review. Copyright © 2014 Elsevier B.V. All rights reserved.
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Microenvironment of Breast Tissue: Lithocholic Acid and Other Intestinal Steroids.
1997-09-01
6. chenodeoxycholic acid -7-sulfate 7. ursodeoxycholic acid 8. glycodeoxycholic acid 9. 3ß-hydroxy-5-cholenoic acid sulfate 10. cholicacid 11. 3a... acids 7 Ursodeoxycholic acid 29.1 10 Cholic acid 32.5 11 3ß,7a-Dihydroxy-chol-5-enoicacidJ 33.3 12 7a-Hydroxy-3-oxo-chol-4-enoic acidc 34.1 16...AD GRANT NUMBER DAMD17-94-J-4311 TITLE: Microenvironment of: Breast Tissue: Lithocholic Acid and Other Intestinal Steroids PRINCIPAL
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Lee, Kyung Hee; Yoo, Sang-Ho; Baek, Seung Hee; Lee, Hyeon Gyu
2007-07-01
Physicochemical and biological characteristics of the exopolysaccharide, PS7, produced from Beijerinckia indica were investigated. The PS7 weight fractions of Glc and GlcUA were 0.45 and 0.25, respectively, and the molar ratio of Glc:Rha:GalUA was approximately 5:1:1.3. The PS7 was chemically derivatized with diethylaminoethyl chloride-HCl (DEAE-HCl), and the resulting modified PS7 contained both positive and negative charges. The elemental and IR analyses were conducted to confirm the successful incorporation of DEAE groups into PS7. Large increase in nitrogen fraction was observed from the derivatized PS7 by elemental analysis. The characteristic CH(3) and CH(2) peaks originated from DEAE group were detected in (1)H NMR spectrum of the derivatized PS7 as well. Solubility of native PS7 was improved almost twice from 40 to 75% after DEAE-derivatization, while water holding capacity (WHC) drastically decreased from 10,026 to 245%. Oil binding capacity (OBC) of PS7 also significantly dropped from 1528 to 331% after the derivatization. The [eta] values of native and derivatized PS7 were 27.6 and 0.31 dL/g at 25 degrees C, respectively, which means that the DEAE-derivatization significantly decreased the [eta] of PS7. The bile acid binding capacity of PS7 was indirectly determined by measuring the holding capability of cholic acid inside the dialysis membrane. When PS7 was DEAE-derivatized, there was substantial decrease in the cholic acid retardation index (CRI). Up to 8-9h of dialysis, the derivatized PS7 hold 8.6% less of cholic acid compared to native one.
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Dayal, B; Tint, G S; Batta, A K; Shefer, S; Salen, G; Bose, A K; Pramanik, B N
1983-02-01
This paper describes the chemical synthesis of 3 alpha,7 alpha,12 alpha,25-tetrahydroxy-5 beta-cholestan-24-one via selective oxidation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha, 24 xi,25-pentol with silver carbonate on celite. The structure of this 24-keto bile alcohol was confirmed by gas-liquid chromatography and mass spectrometry. Synthesis of this compound via pyridinium chlorochromate oxidation of the triacetoxy derivative of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24 xi,25-pentol followed by saponification further established its structure. 3 alpha,7 alpha,12 alpha,25-Tetrahydroxy-5 beta-cholestan-24-one was required for the in vivo and in vitro studies of side-chain oxidation and cleavage in the 25-hydroxylation pathway of cholic acid biosynthesis.
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[Effects of high cholic acid on fetal brains of pregnant rats].
Tan, Li; Ding, Yi-ling
2007-12-01
To investigate the effects of morphous on fetal brains in pregnant rat of high cholic acid. Randomly deviding 30 SD pregnant rats to three groups A, B and C, every group is 10. From 13th to 20th days of pregnancy, injecting 5.5 mg x kg(-1) x d(-1) cholic acid to pregnant rats of group A, 1.4 mg x kg(-1) x d(-1) cholic acid to group B and the partes aequales normal saline to group C by intraperitoneal injection one time every day. In the 21st day of pregancy, to cut the belly open and take the fetus out and record the total fetus, live fetus and the weight. Determine the serum concentration of total bile acid (TBA) in pregnant rats and fetal rats. Enzyme linked immunosorbent assay(ELISA) was used to detect the serum level of neuron-specific enolase (NSE) in fetal rats. Fix and embed the brain after decapitation, then to observe the pathological change of the fetal cerebrum under light microscope and electron microscope. (1) The serum concentration of TBA of pregnant rats and fetal rats in group A is (22.3 +/- 8.1) micromol/L and (28.8 +/- 8.1) micromol/L, in group B is (9.8 +/- 3.6) micromol/L and (9.3 +/- 3.5) micromol/L, in group C is (3.6 +/- 1.8) micromol/L and (4.0 +/- 1.2) micromol/L. There is significant defference in every two groups, P < 0.01. The serum concentration of TBA between pregnant rats and fetal rats were positively correlated with each other, (r = 0.875, P < 0.01). (2) The mortinatality of fetus in group A, B and C are 30.1%, 16.9% and 7.1%, there is significant defference in every two groups, P < 0.05. (3) The serum lever of NSE of fetus in group A was significantly higher than that of group B and C, [(31.9 +/- 13.1) ng/L vs. (13.9 +/- 5.9) ng/L and (9.3 +/- 3.9) ng/L, both are P < 0.05]. But there is no significant difference between group B and C, P > 0.05. The serum level of TBA and NSE in fetus were positively correlated with each other, (r = 0.758, P < 0.01). (4) By the light microscope we found that the neuronal degeneration and necrosis. The level of organization disorder, the density of nerve cells decrease and the cell nucleus pyknosis and anachromasis. The neuronal degeneration area in group A and B are significantly higher than group C[(1.4 +/- 0.6) and (1.5 +/- 0.7) vs. (0.7 +/- 0.3), both are P < 0.05]. But there is no significant difference between group A and B, P > 0.05. The is no apparente correlation between the neuronal degeneration area and the serum level of NSE in fetus, r = 0.282, P > 0.05. The neuronal necrosis area in group A are significantly higher than group B and C [(1.8 +/- 0.7) vs. (0.9 +/- 0.4) and (0.6 +/- 0.3), both are P < 0.05]. But there is no significant defference between group B and C, P > 0.05. The neuronal necrosis area and the level of NSE in fetus were positively correlated with each other, r = 0.798, P < 0.01. (5) Under the electron microscope we found that the neuronal nuclear membrance ambiguity, karyopycnosis, nucleolus disappeared, nuclear chromatin rarefaction. The number of endoplasmic reticulum and mitochondria decrease, the residual mitochondria swelling, cristae quassation. The number density of mitochondria of nerve cells in group A is significantly lower than that of group B and C [(21.9 +/- 9.0) microm(-3) vs. (45.5 +/- 13.1) microm(-3) and (36.1 +/- 12.1) mcirom(-3), both are P < 0.01]. But there is no significant difference between group B and C, P > 0. 05. The volume of mitochondria of nerve cells in group A and B are significantly higher than that of group C [7.0 +/-1.8) x 10(-4) microm3 and (5.7 +/- 1.6) x 10(-4) microM3 vs. (3.2 +/- 1.2) x 10(-4) microm(3), both are P < 0.01]. But there is no significant difference between group A and B (P > 0.05). There is apparente pathological change of fetal rats brain in cholic acid groups, the neuronal degeneration and the mitochondria swelling was mainly found in low cholic acid group, the neuronal necrosis and the mitochondria decrease was mainly found in high cholic acid group. The serum concentration of TBA and NSE in fetal rats were positively correlated with each other.
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[Combined effect of benzylpenicillin, furagin and bile acids on staphylococci].
Sytnik, I A; Tkachuk, N I
1982-11-01
The results of the study of the effect of benzylpenicillin or furagin in combination with bile acids, such as cholic, glycocholic and desoxycholic on the collection cultures of staphylococci are presented. The study showed that the subbacteriostatic doses of the bile acids increased the bacteriostatic and bactericidal effects of benzylpenicillin and furagin by tens and hundreds times. The highest potentiation effect was attained with the use of the furagin combination and desoxycholic acid.
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Physicochemical properties and biological activities of DEAE-derivatized Sphingomonas gellan.
Yoo, Sang-Ho; Lee, Kyung Hee; Lee, Ji-Soo; Cha, Jaeho; Park, Cheon Seok; Lee, Hyeon Gyu
2005-08-10
Physicochemical characteristics and biological activities of Sphingomonas gellan (S-gellan) were investigated. The S-gellan weight fractions of Glc and GlcUA were 0.45 and 0.25, respectively, and the molar ratio of Glc:Rha:GlcUA was approximately 4:2:3. The S-gellan was chemically derivatized with diethylaminoethyl chloride-HCl (DEAE-HCl), and the resulting modified S-gellan contained both positive and negative charges. The elemental and IR analyses were conducted to confirm the successful incorporation of DEAE groups into S-gellan. A large increase in nitrogen fraction was observed from the derivatized S-gellan by elemental analysis. The IR absorption bands induced by C-H, C-N, and C-O-C stretching were noticeable at 2950, 1310-1380, and 1000-1150 cm(-1), respectively, resulting from the DEAE substitution. The characteristic CH3 and CH2 peaks originated from the DEAE group were detected in the 1H NMR spectrum of the derivatized S-gellan as well. The solubility of native S-gellan was improved almost twice from 40% to 75% after DEAE derivatization, while water holding capacity (WHC) drastically decreased from 10026% to 245%. Oil binding capacity (OBC) of S-gellan also significantly dropped from 1528% to 331% after the derivatization. The bile acid binding capacity of S-gellan was indirectly determined by measuring the holding capability of cholic acid inside the dialysis membrane (MWCO 12,000-14,000 Da). Once S-gellan was DEAE derivatized, there was substantial increase in the cholic acid retardation index (CRI). Up to 9 h of dialysis, the derivatized S-gellan released 29.3% less of cholic acid compared to the control group that did not contain S-gellan. From these results of the improved water solubility and stronger bile acid binding capacity, it would be suggested that the DEAE-derivatized S-gellan has more advantages than gellan itself for functional food applications.
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The bile acid composition of crane gallbladder bile
Serafin, J.A.
1983-01-01
1. The biliary bile acids of the whooping crane (Grus americana) and the Florida sandhill crane (G. canadensis pratensis) have been examined.2. Cholic acid (CA), chenodeoxycholic acid (CDOCA) and lithocholic acid were found in bile from both species of these North American cranes.3. CDOCA and CA were the primary bile acids in both species, together constituting 70% or more of the bile acids by weight.4. The primary bile acids of cranes appear to be the same as those that have been identified in other avian species.
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Subramaniam, Pushpa; Clayton, Peter T; Portmann, Bernard C; Mieli-Vergani, Giorgina; Hadzić, Nedim
2010-01-01
We studied the clinical features of children with 3beta-hydroxy-Delta 5-C27-steroid dehydrogenase (3beta-HSDH) deficiency presenting to King's College and Great Ormond Street hospitals between 1989 and 2005. The diagnosis was made biochemically by detection of sulphated dihydroxycholenoic acids and trihydroxycholenoic acids in urine by fast atom bombardment mass spectrometry or electrospray ionisation tandem mass spectrophotometry and a plasma bile acid profile showing absent or low cholic and chenodeoxycholic acid levels and high concentrations of 3beta-7 alpha-dihydroxy-5-cholenoic acid and 3beta-7 alpha-12 alpha-trihydroxy-5-cholenoic acid. Eighteen children (12 male) with 3beta-HSDH deficiency were identified and diagnosed at a median age of 1.35 years (range 8 weeks-11 years). The presenting features included neonatal cholestasis (n = 11), rickets (n = 8, 1 of whom also had hypocalcaemic tetany, seizures, and normal liver biochemical markers), hepatomegaly (n = 7), pruritus (n = 3), and steatorrhoea and failure to thrive (n = 3). Ten children had low serum 25-OH vitamin D levels, of whom 8 also had low vitamin E and 6 had low vitamin A serum levels. Liver histology showed giant cell change and hepatocyte disarray in all with added features of cholestasis in 11, bridging fibrosis in 6, micronodular cirrhosis in 1, fatty change in 1, and active lobular and portal inflammation in 1. Five patients were treated with cholic acid and chenodeoxycholic acid (7 mg x kg(-1) x day(-1) of each), 7 with chenodeoxycholic acid only (7-18 mg x kg(-1) x day(-1)), and 1 with cholic acid (8 mg x kg(-1) x day(-1)) only. Repeated liver biopsies performed in 4 patients 6 months after starting replacement therapy showed improved histological changes. Three children died untreated before 5 years of age. After a median follow-up of 5.5 years (range 1-17 years) 12 out of 13 treated children have no clinical signs of liver disease or of fat-soluble vitamin deficiency. 3beta-HSDH deficiency is a rare inborn error of metabolism with diverse clinical features. Early replacement treatment leads to clinical and biochemical control and prevents chronic liver and bone disease, at least in the medium term.
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Effects of bile acids on human airway epithelial cells: implications for aerodigestive diseases.
Aldhahrani, Adil; Verdon, Bernard; Ward, Chris; Pearson, Jeffery
2017-01-01
Gastro-oesophageal reflux and aspiration have been associated with chronic and end-stage lung disease and with allograft injury following lung transplantation. This raises the possibility that bile acids may cause lung injury by damaging airway epithelium. The aim of this study was to investigate the effect of bile acid challenge using the immortalised human bronchial epithelial cell line (BEAS-2B). The immortalised human bronchial epithelial cell line (BEAS-2B) was cultured. A 48-h challenge evaluated the effect of individual primary and secondary bile acids. Post-challenge concentrations of interleukin (IL)-8, IL-6 and granulocyte-macrophage colony-stimulating factor were measured using commercial ELISA kits. The viability of the BEAS-2B cells was measured using CellTiter-Blue and MTT assays. Lithocholic acid, deoxycholic acid, chenodeoxycholic acid and cholic acid were successfully used to stimulate cultured BEAS-2B cells at different concentrations. A concentration of lithocholic acid above 10 μmol·L -1 causes cell death, whereas deoxycholic acid, chenodeoxycholic acid and cholic acid above 30 μmol·L -1 was required for cell death. Challenge with bile acids at physiological levels also led to a significant increase in the release of IL-8 and IL6 from BEAS-2B. Aspiration of bile acids could potentially cause cell damage, cell death and inflammation in vivo . This is relevant to an integrated gastrointestinal and lung physiological paradigm of chronic lung disease, where reflux and aspiration are described in both chronic lung diseases and allograft injury.
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Agarwal, Devesh S; Singh, Rajnish Prakash; Lohitesh, K; Jha, Prabhat N; Chowdhury, Rajdeep; Sakhuja, Rajeev
2017-12-13
A series of amino-substituted [Formula: see text]-cyanostilbene derivatives and their bile acid (cholic and deoxycholic acid) amides were designed and synthesized. A comparative study on the anticancer and antibacterial activity evaluation on the synthesized analogs was carried against the human osteosarcoma (HOS) cancer cell line, and two gram -ve (E. coli and S. typhi) and two gram [Formula: see text]ve (B. subtilis and S. aureus) bacterial strains. All the cholic acid [Formula: see text]-cyanostilbene amides showed an [Formula: see text] in the range 2-13 [Formula: see text] against human osteosarcoma cells (HOS) with the most active analog (6g) possessing an [Formula: see text] of [Formula: see text]. One of the amino-substituted [Formula: see text]-cyanostilbene, 4e, was found to possess an [Formula: see text] of [Formula: see text]. An increase in the number of cells at the sub-[Formula: see text] phase of the cell was observed in the in vitro cell cycle analysis of two most active compounds in the series (4e, 6g) suggesting a clear indication toward induction of apoptotic cascade. With respect to antibacterial screening, amino-substituted [Formula: see text]-cyanostilbenes were found to be more active than their corresponding bile acid amides. The synthesized compounds were also subjected to in silico study to predict their physiochemical properties and drug-likeness score.
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Mice with chimeric livers are an improved model for human lipoprotein metabolism.
Ellis, Ewa C S; Naugler, Willscott Edward; Nauglers, Scott; Parini, Paolo; Mörk, Lisa-Mari; Jorns, Carl; Zemack, Helen; Sandblom, Anita Lövgren; Björkhem, Ingemar; Ericzon, Bo-Göran; Wilson, Elizabeth M; Strom, Stephen C; Grompe, Markus
2013-01-01
Rodents are poor model for human hyperlipidemias because total cholesterol and low density lipoprotein levels are very low on a normal diet. Lipoprotein metabolism is primarily regulated by hepatocytes and we therefore assessed whether chimeric mice extensively repopulated with human cells can model human lipid and bile acid metabolism. FRG [ F ah(-/-) R ag2(-/-)Il2r g (-/-)]) mice were repopulated with primary human hepatocytes. Serum lipoprotein lipid composition and distribution (VLDL, LDL, and HDL) was analyzed by size exclusion chromatography. Bile was analyzed by LC-MS or by GC-MS. RNA expression levels were measured by quantitative RT-PCR. Chimeric mice displayed increased LDL and VLDL fractions and a lower HDL fraction compared to wild type, thus significantly shifting the ratio of LDL/HDL towards a human profile. Bile acid analysis revealed a human-like pattern with high amounts of cholic acid and deoxycholic acid (DCA). Control mice had only taurine-conjugated bile acids as expcted, but highly repopulated mice had glycine-conjugated cholic acid as found in human bile. RNA levels of human genes involved in bile acid synthesis including CYP7A1, and CYP27A1 were significantly upregulated as compared to human control liver. However, administration of recombinant hFGF19 restored human CYP7A1 levels to normal. Humanized-liver mice showed a typical human lipoprotein profile with LDL as the predominant lipoprotein fraction even on a normal diet. The bile acid profile confirmed presence of an intact enterohepatic circulation. Although bile acid synthesis was deregulated in this model, this could be fully normalized by FGF19 administration. Taken together these data indicate that chimeric FRG-mice are a useful new model for human lipoprotein and bile-acid metabolism.
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Zang, Qing-Ce; Wang, Jia-Bo; Kong, Wei-Jun; Jin, Cheng; Ma, Zhi-Jie; Chen, Jing; Gong, Qian-Feng; Xiao, Xiao-He
2011-12-01
The fingerprints of artificial Calculus bovis extracts from different solvents were established by ultra-performance liquid chromatography (UPLC) and the anti-bacterial activities of artificial C. bovis extracts on Staphylococcus aureus (S. aureus) growth were studied by microcalorimetry. The UPLC fingerprints were evaluated using hierarchical clustering analysis. Some quantitative parameters obtained from the thermogenic curves of S. aureus growth affected by artificial C. bovis extracts were analyzed using principal component analysis. The spectrum-effect relationships between UPLC fingerprints and anti-bacterial activities were investigated using multi-linear regression analysis. The results showed that peak 1 (taurocholate sodium), peak 3 (unknown compound), peak 4 (cholic acid), and peak 6 (chenodeoxycholic acid) are more significant than the other peaks with the standard parameter estimate 0.453, -0.166, 0.749, 0.025, respectively. So, compounds cholic acid, taurocholate sodium, and chenodeoxycholic acid might be the major anti-bacterial components in artificial C. bovis. Altogether, this work provides a general model of the combination of UPLC chromatography and anti-bacterial effect to study the spectrum-effect relationships of artificial C. bovis extracts, which can be used to discover the main anti-bacterial components in artificial C. bovis or other Chinese herbal medicines with anti-bacterial effects. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Lee, Yeonmi; Yoshitsugu, Reika; Kikuchi, Keidai; Joe, Ga-Hyun; Tsuji, Misaki; Nose, Takuma; Shimizu, Hidehisa; Hara, Hiroshi; Minamida, Kimiko; Miwa, Kazunori; Ishizuka, Satoshi
2016-08-01
Intestinal bacteria are involved in bile acid (BA) deconjugation and/or dehydroxylation and are responsible for the production of secondary BA. However, an increase in the production of secondary BA modulates the intestinal microbiota due to the bactericidal effects and promotes cancer risk in the liver and colon. The ingestion of Bacillus coagulans improves constipation via the activation of bowel movement to promote defaecation in humans, which may alter BA metabolism in the intestinal contents. BA secretion is promoted with high-fat diet consumption, and the ratio of cholic acid (CA):chenodeoxycholic acid in primary BA increases with ageing. The dietary supplementation of CA mimics the BA environment in diet-induced obesity and ageing. We investigated whether B. coagulans lilac-01 and soya pulp influence both BA metabolism and the maintenance of host health in CA-supplemented diet-fed rats. In CA-fed rats, soya pulp significantly increased the production of secondary BA such as deoxycholic acid and ω-muricholic acids, and soya pulp ingestion alleviated problems related to plasma adiponectin and gut permeability in rats fed the CA diet. The combination of B. coagulans and soya pulp successfully suppressed the increased production of secondary BA in CA-fed rats compared with soya pulp itself, without impairing the beneficial effects of soya pulp ingestion. In conclusion, it is possible that a combination of prebiotics and probiotics can be used to avoid an unnecessary increase in the production of secondary BA in the large intestine without impairing the beneficial functions of prebiotics.
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Repa, J J; Lund, E G; Horton, J D; Leitersdorf, E; Russell, D W; Dietschy, J M; Turley, S D
2000-12-15
Sterol 27-hydroxylase (CYP27) participates in the conversion of cholesterol to bile acids. We examined lipid metabolism in mice lacking the Cyp27 gene. On normal rodent chow, Cyp27(-/-) mice have 40% larger livers, 45% larger adrenals, 2-fold higher hepatic and plasma triacylglycerol concentrations, a 70% higher rate of hepatic fatty acid synthesis, and a 70% increase in the ratio of oleic to stearic acid in the liver versus Cyp27(+/+) controls. In Cyp27(-/-) mice, cholesterol 7alpha-hydroxylase activity is increased 5-fold, but bile acid synthesis and pool size are 47 and 27%, respectively, of those in Cyp27(+/+) mice. Intestinal cholesterol absorption decreases from 54 to 4% in knockout mice, while fecal neutral sterol excretion increases 2.5-fold. A compensatory 2.5-fold increase in whole body cholesterol synthesis occurs in Cyp27(-/-) mice, principally in liver, adrenal, small intestine, lung, and spleen. The mRNA for the cholesterogenic transcription factor sterol regulatory element-binding protein-2 (SREBP-2) and mRNAs for SREBP-2-regulated cholesterol biosynthetic genes are elevated in livers of mutant mice. In addition, the mRNAs encoding the lipogenic transcription factor SREBP-1 and SREBP-1-regulated monounsaturated fatty acid biosynthetic enzymes are also increased. Hepatic synthesis of fatty acids and accumulation of triacylglycerols increases in Cyp27(-/-) mice and is associated with hypertriglyceridemia. Cholic acid feeding reverses hepatomegaly and hypertriglyceridemia but not adrenomegaly in Cyp27(-/-) mice. These studies confirm the importance of CYP27 in bile acid synthesis and they reveal an unexpected function of the enzyme in triacylglycerol metabolism.
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Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review
Tonin, Fabio
2018-01-01
Ursodeoxycholic acid (UDCA) is a pharmaceutical ingredient widely used in clinics. As bile acid it solubilizes cholesterol gallstones and improves the liver function in case of cholestatic diseases. UDCA can be obtained from cholic acid (CA), which is the most abundant and least expensive bile acid available. The now available chemical routes for the obtainment of UDCA yield about 30% of final product. For these syntheses several protection and deprotection steps requiring toxic and dangerous reagents have to be performed, leading to the production of a series of waste products. In many cases the cholic acid itself first needs to be prepared from its taurinated and glycilated derivatives in the bile, thus adding to the complexity and multitude of steps involved of the synthetic process. For these reasons, several studies have been performed towards the development of microbial transformations or chemoenzymatic procedures for the synthesis of UDCA starting from CA or chenodeoxycholic acid (CDCA). This promising approach led several research groups to focus their attention on the development of biotransformations with non-pathogenic, easy-to-manage microorganisms, and their enzymes. In particular, the enzymatic reactions involved are selective hydrolysis, epimerization of the hydroxy functions (by oxidation and subsequent reduction) and the specific hydroxylation and dehydroxylation of suitable positions in the steroid rings. In this minireview, we critically analyze the state of the art of the production of UDCA by several chemical, chemoenzymatic and enzymatic routes reported, highlighting the bottlenecks of each production step. Particular attention is placed on the precursors availability as well as the substrate loading in the process. Potential new routes and recent developments are discussed, in particular on the employment of flow-reactors. The latter technology allows to develop processes with shorter reaction times and lower costs for the chemical and enzymatic reactions involved. PMID:29520309
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Binding of bile acids by pastry products containing bioactive substances during in vitro digestion.
Dziedzic, Krzysztof; Górecka, Danuta; Szwengiel, Artur; Smoczyńska, Paulina; Czaczyk, Katarzyna; Komolka, Patrycja
2015-03-01
The modern day consumer tends to choose products with health enhancing properties, enriched in bioactive substances. One such bioactive food component is dietary fibre, which shows a number of physiological properties including the binding of bile acids. Dietary fibre should be contained in everyday, easily accessible food products. Therefore, the aim of this study was to determine sorption capacities of primary bile acid (cholic acid - CA) and secondary bile acids (deoxycholic - DCA and lithocholic acids - LCA) by muffins (BM) and cookies (BC) with bioactive substances and control muffins (CM) and cookies (CC) in two sections of the in vitro gastrointestinal tract. Variations in gut flora were also analysed in the process of in vitro digestion of pastry products in a bioreactor. Enzymes: pepsin, pancreatin and bile salts: cholic acid, deoxycholic acid and lithocholic acid were added to the culture. Faecal bacteria, isolated from human large intestine, were added in the section of large intestine. The influence of dietary fibre content in cookies and concentration of bile acids in two stages of digestion were analysed. Generally, pastry goods with bioactive substances were characterized by a higher content of total fibre compared with the control samples. These products also differ in the profile of dietary fibre fractions. Principal Component Analysis (PCA) showed that the bile acid profile after two stages of digestion depends on the quality and quantity of fibre. The bile acid profile after digestion of BM and BC forms one cluster, and with the CM and CC forms a separate cluster. High concentration of H (hemicellulose) is positively correlated with LCA (low binding effect) and negatively correlated with CA and DCA contents. The relative content of bile acids in the second stage of digestion was in some cases above the content in the control sample, particularly LCA. This means that the bacteria introduced in the 2nd stage of digestion synthesize the LCA.
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Doden, Heidi; Sallam, Lina A; Devendran, Saravanan; Ly, Lindsey; Doden, Greta; Daniel, Steven L; Alves, João M P; Ridlon, Jason M
2018-05-15
Bile acids are important cholesterol-derived nutrient signaling hormones, synthesized in the liver, that act as detergents to solubilize dietary lipids. Bile acid 7α-dehydroxylating gut bacteria generate the toxic bile acids deoxycholic acid and lithocholic acid from host bile acids. The ability of these bacteria to remove the 7-hydroxyl group is partially dependent on 7α-hydroxysteroid dehydrogenase (HSDH) activity, which reduces 7-oxo-bile acids generated by other gut bacteria. 3α-HSDH has an important enzymatic activity in the bile acid 7α-dehydroxylation pathway. 12α-HSDH activity has been reported for the low-activity bile acid 7α-dehydroxylating bacterium Clostridium leptum ; however, this activity has not been reported for high-activity bile acid 7α-dehydroxylating bacteria, such as Clostridium scindens , Clostridium hylemonae , and Clostridium hiranonis Here, we demonstrate that these strains express bile acid 12α-HSDH. The recombinant enzymes were characterized from each species and shown to preferentially reduce 12-oxolithocholic acid to deoxycholic acid, with low activity against 12-oxochenodeoxycholic acid and reduced activity when bile acids were conjugated to taurine or glycine. Phylogenetic analysis suggests that 12α-HSDH is widespread among Firmicutes , Actinobacteria in the Coriobacteriaceae family, and human gut Archaea IMPORTANCE 12α-HSDH activity has been established in the medically important bile acid 7α-dehydroxylating bacteria C. scindens , C. hiranonis , and C. hylemonae Experiments with recombinant 12α-HSDHs from these strains are consistent with culture-based experiments that show a robust preference for 12-oxolithocholic acid over 12-oxochenodeoxycholic acid. Phylogenetic analysis identified novel members of the gut microbiome encoding 12α-HSDH. Future reengineering of 12α-HSDH enzymes to preferentially oxidize cholic acid may provide a means to industrially produce the therapeutic bile acid ursodeoxycholic acid. In addition, a cholic acid-specific 12α-HSDH expressed in the gut may be useful for the reduction in deoxycholic acid concentration, a bile acid implicated in cancers of the gastrointestinal (GI) tract. Copyright © 2018 American Society for Microbiology.
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[Joint action of nitrofuran preparations and bile acids on bacteria of the genus Proteus].
Sytnik, I A; Puzakova, E V
1975-01-01
Sensitivity of 25 fresh isolates of Proteus to some nitrofuran drugs most widely used in the clinical practice, such as furacillin, furagin, furazolidone and nitrofurantoin was studied. When the drugs were used in combination with some bile acids, i.e. desoxycholic, dehydrocholic, cholic and glycocholic acids, significant in vitro potentiation of the antibacterial activity of the nitrofurans against the isolates was observed. The combinations of the drugs with desoxycholic acid proved to be most effective. In the presence of this acid the bacteriostatic dose of the drugs decreased several thousand times. Combination of the nitrofurans with the other acids resulted in an increase in the antimicrobial activity amounting to several hundred times. The combinations of the drugs with the bile acids had not only bacteriostatic but also bactericidal effect.
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[Correlations of bile acids in the bile of rats in conditions of alloxan induced diabetes melitus].
Danchenko, N M; Vesel'skyĭ, S P; Tsudzevych, B O
2014-01-01
The ratio of bile acids in the bile of rats with alloxan diabetes was investigated using the method of thin-layer chromatography. Changes of coefficients of conjugation and hydroxylation of bile acids were calculated and analyzed in half-hour samples of bile obtained during the 3-hour experiment. It has been found that the processes of conjugation of cholic acid with glycine and taurine are inhibited in alloxan diabetes. At the same time a significant increase of free threehydroxycholic and dixydroxycholic bile acids and conjugates of the latter ones with taurine has been registered. Coefficients of hydroxylation in alloxan diabetes show the domination of "acidic" pathway in bile acid biosynthesis that is tightly connected with the activity of mitochondrial enzymes.
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NASA Astrophysics Data System (ADS)
Roy, Nayan; Paul, Pradip C.; Singh, T. Sanjoy
2015-05-01
Fluorescence properties of Schiff base - N,N‧-bis(salicylidene) - 1,2-phenylenediamine (LH2) is used to study the micelles formed by aggregation of different important bile acids like cholic acid, deoxycholic acid, chenodeoxycholic acid and glycocholic acid by steady state and picosecond time-resolved fluorescence spectroscopy. The fluorescence band intensity was found out to increase with concomitant red shift with gradual addition of different bile acids. Binding constant of the probe with different bile acids as well as critical micelle concentration was obtained from the variation of fluorescence intensity on increasing concentration of bile acids in the medium. The increase in fluorescence quantum yields, fluorescence decay times and substantial decrease in nonradiative decay rate constants in bile acids micellar environment points to the restricted motion of the fluorophore inside the micellar subdomains.
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Solubilization of active opiate receptors.
Simonds, W F; Koski, G; Streaty, R A; Hjelmeland, L M; Klee, W A
1980-01-01
Receptors that reversibly bind opiates and opioid peptides have been solubilized from brain and neuroblastoma-glioma hybrid cell NG108-15 membranes. Active receptors are specifically solubilized with a new type of detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, which is a zwitterionic derivative of cholic acid. The solubilized receptor complexes behave as large molecules with a Stokes radius of 70 A and contain protein as an essential constituent. PMID:6254034
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Amphiphilically modified chitosan cationic nanoparticles for drug delivery
NASA Astrophysics Data System (ADS)
You, Jie; Li, Wenfeng; Yu, Chang; Zhao, Chengguang; Jin, Langping; Zhou, Yili; Xu, Xuzhong; Dong, Siyang; Lu, Xincheng; Wang, Ouchen
2013-12-01
A series of amphiphilic N-(2-hydroxy)propyl-3-trimethylammonium-chitosan-cholic acid (HPTA-CHI-CA) polymers were synthesized by grafting cholic acid (CA) and glycidyltrimethylammonium chloride onto chitosan. The self-assembly behavior of HPTA-CHI-CA was studied by fluorescence technique. The polymers were able to self-assemble into NPs in phosphate buffered saline with a critical aggregation concentration (CAC) in the range of 66-26 mg/L and the CAC decreased with the increasing of the degree of substitution (DS) of CA. The size of cationic HPTA-CHI-CA NPs ranges from 170 to 220 nm (PDI < 0.2). It was found that doxorubicin (DOX) could be encapsulated into HPTA-CHI-CA NPs based on self-assembly. The drug loading content and efficiency varies depending on the DS of CA and feeding ratio of DOX to polymer. In vitro release studies suggested that DOX released slowly from HPTA-CHI-CA NPs without any burst initial release. Besides, the confocal microscopic measurements indicated that DOX-HPTA-CHI-CA NPs could easily be uptaken by breast cancer (MCF-7) cells and release DOX in cytoplasm. Anti-tumor efficacy results showed that DOX-HPTA-CHI-CA NPs have a significant activity of inhibition MCF-7 cells growth. These results suggest cationic HPTA-CHI-CA may have great potential for anticancer drug delivery.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Galatola, G.; Jazrawi, R.P.; Bridges, C.
The purpose of this study was to develop and validate a method of directly measuring ileal bile acid absorption efficiency during a single enterohepatic cycle (first-pass ileal clearance). This has become feasible for the first time because of the availability of the synthetic gamma-labeled bile acid 75Selena-homocholic acid-taurine (75SeHCAT). Together with the corresponding natural bile acid cholic acid-taurine (labeled with 14C), SeHCAT was infused distal to an occluding balloon situated beyond the ampulla of Vater in six healthy subjects. Completion of a single enterohepatic cycle was assessed by obtaining a plateau for 75SeHCAT activity proximal to the occluding balloon, whichmore » prevented further cycles. Unabsorbed 75SeHCAT was collected after total gut washout, which was administered distal to the occluding balloon. 75SeHCAT activity in the rectal effluent measured by gamma counter was compared with that of absorbed 75SeHCAT level measured by gamma camera and was used to calculate first-pass ileal clearance. This was very efficient (mean value, 96%) and showed very little variation in the six subjects studied (range, 95%-97%). A parallel time-activity course in hepatic bile for 14C and 75Se during a single enterohepatic cycle, together with a ratio of unity for 14C/75Se in samples obtained at different time intervals, suggests that 75SeHCAT is handled by the ileum like the natural bile acid cholic acid-taurine. Extrapolation of 75SeHCAT first-pass ileal clearance to that of the natural bile acid therefore seems justifiable. In a subsidiary experiment, ileal absorption efficiency per day for 75SeHCAT was also measured by scanning the gallbladder area on 5 successive days after the measurement of first-pass ileal clearance. In contrast with absorption efficiency per cycle, absorption efficiency per day varied widely (49%-86%).« less
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Nonchemically amplified resists for deep-UV lithography
NASA Astrophysics Data System (ADS)
Ganesan, Ramakrishnan; Kim, Sumin; Youn, Seul Ki; Cho, Youngook; Yun, Jei-Moon; Kim, Jin-Baek
2007-03-01
A novel monomer containing a diazoketo functional group was designed and synthesized. Polymers were synthesized using the diazoketo-functionalized monomer and their physical properties were evaluated. The polymers were synthesized by radical copolymerization of cholic acid 3-diazo-3-ethoxycarbonyl-2-oxo-propyl ester methacrylate, methyl methacrylate, and γ-butyrolacton-2-yl methacrylate. These polymers showed 0.7 μm line and space patterns using a mercury-xenon lamp in a contact printing mode.
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Swobodnik, W; Klüppelberg, U; Wechsler, J G; Volz, M; Normandin, G; Ditschuneit, H
1985-05-03
This paper introduces a new method to detect the taurine and glycine conjugates of five different bile acids (cholic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid and lithocholic acid) in human bile. Advantages of this method are sufficient separation of compounds within a short period of time and a high rate of reproducibility. Using a mobile phase gradient of acetonitrile and water, modified with tetrabutylammonium hydrogen sulphate (0.0075 mol/l), we were able to maximize the differentiation between ursodeoxycholic acid and lithocholic acid, which is of primary interest during conservative gallstone dissolution therapy. Use of this gradient reduced analysis time to less than 0.5 h. Recovery rates for this modified method ranged from 94% to 100%, and reproducibility was 98%, sufficient for routine clinical applications.
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Genin, Michael J; Gonzalez Valcarcel, Isabel C; Holloway, William G; Lamar, Jason; Mosior, Marian; Hawkins, Eric; Estridge, Thomas; Weidner, Jeffrey; Seng, Thomas; Yurek, David; Adams, Lisa A; Weller, Jennifer; Reynolds, Vincent L; Brozinick, Joseph T
2016-06-23
To develop novel treatments for type 2 diabetes and dyslipidemia, we pursued inhibitors of serine palmitoyl transferase (SPT). To this end compounds 1 and 2 were developed as potent SPT inhibitors in vitro. 1 and 2 reduce plasma ceramides in rodents, have a slight trend toward enhanced insulin sensitization in DIO mice, and reduce triglycerides and raise HDL in cholesterol/cholic acid fed rats. Unfortunately these molecules cause a gastric enteropathy after chronic dosing in rats.
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Solid polymeric electrolyte based dye-sensitized solar cell with improved stability
NASA Astrophysics Data System (ADS)
Prasad, Narottam; Kumar, Manish; Patel, K. R.; Roy, M. S.
2018-05-01
The impact of polymeric electrolyte was investigated over the performance of dye-sensitized solar cell made with Rose Bengal as sensitizer. Further, the selective influence of TiCl4 treatment and pre-sensitizer deoxycholic acid on nc-TiO2 photoanode was determined in terms of improvement in conversion efficiency of the cell. It is found that the effect of TiCl4 treatment was comparatively more than pre-sensitization with de-oxy cholic acid towards improving the efficiency of the cell. The conversion efficiency on TiCl4 treatment was 0.2% whereas on pre-sensitization with deoxy chollic acid it was 0.1%. The combined effect of both TiCl4 treatment & pre-sensitization with deoxycholic acid leads conversion efficiency to 0.33%.
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Iida, T; Momose, T; Chang, F C; Goto, J; Nambara, T
1989-12-01
The 4 beta-hydroxylated derivatives of lithocholic, deoxycholic, chenodeoxycholic, and cholic acids were synthesized from their respective parent compounds. The principal reactions employed were 1) beta-face cis-dihydroxylation of delta 3 intermediates with osmium tetroxide-N-methylmorpholine N-oxide, 2) selective cathylation of vicinal 3 beta,4 beta-diols followed by oxidation of the resulting 4 beta-monocathylates, or direct selective oxidation at C-3 of 3 beta,4 beta-diols with pyridinium chlorochromate, and 3) stereoselective reduction of the 3-oxo compounds with tert-butylamine-borane complex. The results of analysis of the prepared 4 beta-hydroxylated bile acids with a diequatorial trans-glycol structure and their 3 beta-epimers by proton and carbon-13 nuclear magnetic resonance spectroscopies are briefly discussed along with the mass spectrometric properties.
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Taurocholic acid metabolism by gut microbes and colon cancer
Ridlon, Jason M.; Wolf, Patricia G.; Gaskins, H. Rex
2016-01-01
ABSTRACT Colorectal cancer (CRC) is one of the most frequent causes of cancer death worldwide and is associated with adoption of a diet high in animal protein and saturated fat. Saturated fat induces increased bile secretion into the intestine. Increased bile secretion selects for populations of gut microbes capable of altering the bile acid pool, generating tumor-promoting secondary bile acids such as deoxycholic acid and lithocholic acid. Epidemiological evidence suggests CRC is associated with increased levels of DCA in serum, bile, and stool. Mechanisms by which secondary bile acids promote CRC are explored. Furthermore, in humans bile acid conjugation can vary by diet. Vegetarian diets favor glycine conjugation while diets high in animal protein favor taurine conjugation. Metabolism of taurine conjugated bile acids by gut microbes generates hydrogen sulfide, a genotoxic compound. Thus, taurocholic acid has the potential to stimulate intestinal bacteria capable of converting taurine and cholic acid to hydrogen sulfide and deoxycholic acid, a genotoxin and tumor-promoter, respectively. PMID:27003186
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Effect of Roux-en-Y Gastric Bypass Surgery on Bile Acid Metabolism in Normal and Obese Diabetic Rats
Bhutta, Hina Y; Rajpal, Neetu; White, Wendy; Freudenberg, Johannes M.; Liu, Yaping; Way, James; Rajpal, Deepak; Cooper, David C.; Young, Andrew; Tavakkoli, Ali; Chen, Lihong
2015-01-01
In addition to classic functions of facilitating hepatobiliary secretion and intestinal absorption of lipophilic nutrients, bile acids (BA) are also endocrine factors and regulate glucose and lipid metabolism. Recent data indicate that antiobesity bariatric procedures e.g. Roux-en-Y gastric bypass surgery (RYGB), which also remit diabetes, increase plasma BAs in humans, leading to the hypothesis that BAs may play a role in diabetes resolution following surgery. To investigate the effect of RYGB on BA physiology and its relationship with glucose homeostasis, we undertook RYGB and SHAM surgery in Zucker diabetic fatty (ZDF) and normoglycemic Sprague Dawley (SD) rats and measured plasma and fecal BA levels, as well as plasma glucose, insulin, Glucagon like peptide 1 (GLP-1) and Peptide YY (PYY), 2 days before and 3, 7, 14 and 28 days after surgery. RYGB decreased body weight and increased plasma GLP-1 in both SD and ZDF rats while decreasing plasma insulin and glucose in ZDF rats starting from the first week. Compared to SHAM groups, both SD-RYGB and ZDF-RYGB groups started to have increases in plasma total BAs in the second week, which might not contribute to early post-surgery metabolic changes. While there was no significant difference in fecal BA excretion between SD-RYGB and SD-SHAM groups, the ZDF-RYGB group had a transient 4.2-fold increase (P<0.001) in 24-hour fecal BA excretion on post-operative day 3 compared to ZDF-SHAM, which paralleled a significant increase in plasma PYY. Ratios of plasma and fecal cholic acid/chenodeoxycholic acid derived BAs were decreased in RYGB groups. In addition, tissue mRNA expression analysis suggested early intestinal BA reabsorption and potentially reduced hepatic cholic acid production in RYGB groups. In summary, we present novel data on RYGB-mediated changes in BA metabolism to further understand the role of BAs in RYGB-induced metabolic effects in humans. PMID:25798945
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Improved synthesis of 3 alpha, 7 alpha, 12 alpha, 24 = xi-tetrahydroxy-5 beta-cholestan-26-oic acid.
Batta, A K; Tint, G S; Dayal, B; Shefer, S; Salen, G
1982-06-01
This paper describes three simple and short methods for the conversion of cholic acid into cholylaldehyde with protected hydroxyl groups. The first method involves lithium aluminum hydride reduction of the tetrahydropyranyl ether of methyl cholate and oxidation of the resulting primary alcohol with pyridinium chlorochromate. The second method employs diborane for the reduction of the -COOH group to the -CH2OH group, while the third method involves the reduction of 3 alpha, 7 alpha, 12 alpha-triformyloxy-5 beta-cholan-24-oic acid (as the acid chloride) directly into 3 alpha, 7 alpha, 12 alpha-triformyloxy-5 beta-cholan-24-al with TMA-ferride (tetramethylammonium hydridoirontetracarbonyl). The aldehyde obtained by any of the above methods underwent smooth Reformatsky reaction with ethyl alpha-bromopropionate to yield 3 alpha, 7 alpha, 12 alpha, 24 xi-tetrahydroxy-5 beta-cholestan-26-oic acid.
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Study on bioactive compounds of in vitro cultured Calculus Suis and natural Calculus Bovis.
Wan, Tien-Chun; Cheng, Fu-Yuan; Liu, Yu-Tse; Lin, Liang-Chuan; Sakata, Ryoichi
2009-12-01
The purpose of the study was to investigate bioactive compounds of in vitro cultured Calculus Suis and natural Calculus Bovis obtained as valuable by-products from animals used for meat production. The results showed that the components of natural Calculus Bovis were rich in bilirubin and biliverdin and had higher content of essential amino acids. The major amino acids of in vitro cultured Calculus Suis were identified as glycine, alanine, glutamic acid and aspartic acid, and those for natural Calculus Bovis were found to be glutamic acid, aspartic acid, proline, and arginine. The methionine and cysteine contents of precursors for glutathione in natural Calculus Bovis were significantly higher than those of in vitro cultured Calculus Suis. The mineral contents of zinc, iron and manganese of natural Calculus Bovis were significantly higher than those of in vitro cultured Calculus Suis. The major bile acids in both products were cholic acid and dehydrocholic acid, respectively. The chenodeoxycholic and ursodeoxycholic acid content of in vitro cultured Calculus Suis was significantly higher than that of natural Calculus Bovis.
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Global optimization of cholic acid aggregates
NASA Astrophysics Data System (ADS)
Jójárt, Balázs; Viskolcz, Béla; Poša, Mihalj; Fejer, Szilard N.
2014-04-01
In spite of recent investigations into the potential pharmaceutical importance of bile acids as drug carriers, the structure of bile acid aggregates is largely unknown. Here, we used global optimization techniques to find the lowest energy configurations for clusters composed between 2 and 10 cholate molecules, and evaluated the relative stabilities of the global minima. We found that the energetically most preferred geometries for small aggregates are in fact reverse micellar arrangements, and the classical micellar behaviour (efficient burial of hydrophobic parts) is achieved only in systems containing more than five cholate units. Hydrogen bonding plays a very important part in keeping together the monomers, and among the size range considered, the most stable structure was found to be the decamer, having 17 hydrogen bonds. Molecular dynamics simulations showed that the decamer has the lowest dissociation propensity among the studied aggregation numbers.
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Wu, Yanping; Wang, Zhongyuan; Liu, Gan; Zeng, Xiaowei; Wang, Xusheng; Gao, Yongfeng; Jiang, Lijuan; Shi, Xiaojun; Tao, Wei; Huang, Laiqiang; Mei, Lin
2015-07-01
A novel nanocarrier system of cholic acid (CA) core, star-shaped polymer consisting of poly(D,L-lactide-co-glycolide) (PLGA) was developed for sustained and controlled delivery of simvastatin for chemotherapy of breast adenocarcinoma. The star-shaped polymer CA-PLGA with three branch arms was synthesized successfully through the core-first approach. The simvastatin-loaded star-shaped CA-PLGA nanoparticles were prepared through a modified nanoprecipitation method. The data showed that the fluorescence star-shaped CA-PLGA nanoparticles could be internalized into MDA-MB-231 and MDA-MB-468 human breast cancer cells. The simvastatin-loaded star-shaped CA-PLGA nanoparticles achieved significantly higher level of cytotoxicity than pristine simvastatin and simvastatin-loaded linear PLGA nanoparticles. Moreover, the expression of the cell cycle protein cyclin D1 was dramatically inhibited by simvastatin in both cells, with simvastatin-loaded star-shaped CA-PLGA nanoparticles having the greatest effect. MDA-MB-231 xenograft tumor model on BALB/c nude mice showed that simvastatin-loaded star-shaped CA-PLGA nanoformulations could effectively inhibit the growth of tumor over a longer period of time than pristine simvastatin and simvastatin-loaded linear PLGA nanoformulations at the same dose. In agreement with these, the nuclear expression of proliferation marker Ki-67 in simvastatin-loaded star-shaped CA-PLGA nanoparticles group was reduced to a most extent among four groups through tumor frozen section immunohistochemistry. In conclusion, the star-shaped CA-PLGA polymers could serve as a novel polymeric nanocarrier for breast cancer chemotherapy.
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Gomez-Mendoza, M; Marin, M Luisa; Miranda, Miguel A
2014-11-14
The aim of the present work is to develop two-channel emitters to probe local hydrophobicity by means of fluorescence quenching within different biomimetic supramolecular environments. To achieve this goal, the dansyl (Dns) and tryptophan (Trp) fluorophores have been covalently attached to cholic acid (CA) in order to ensure simultaneous incorporation of the two emitting units into the same compartment. In principle, the two fluorophores of the synthesized Dns-CA-Trp probes could either exhibit an orthogonal behavior or display excited state interactions. The fluorescence spectra of 3β-Dns-CA-Trp showed a residual Trp emission band at ca. 350 nm and an enhanced Dns maximum in the 500-550 nm region. This reveals a partial intramolecular energy transfer, which is consistent with the Dns and Trp singlet energies. Thus, the two photoactive units are not orthogonal; nevertheless, 3β-Dns-CA-Trp seems appropriate as a two-channel reporter for the supramolecular systems of interest. Fluorescence quenching of 3β-Dns-CA-Trp by iodide (which remains essentially in bulk water) was examined within sodium cholate, sodium taurocholate, sodium deoxycholate and mixed micelles. Interestingly, a decrease in the emission intensity of the two bands was observed with increasing iodide concentrations. The most remarkable effect was observed for mixed micelles, where the quenching rate constants were one order of magnitude lower than in solution. As anticipated, the quenching efficiency by iodide decreased with increasing hydrophobicity of the microenvironment, a trend that can be correlated with the relative accessibility of the probe to the ionic quencher.
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Alagona, Giuliano; Ghio, Caterina; Iuliano, Anna; Monti, Susanna; Pieraccini, Ilaria; Salvadori, Piero
2003-04-18
CD spectra of the chiral auxiliaries for enantioselective HPLC N-allyl-N'-methyl-3,12-bis(2-naphthyl)carbamoyloxy-7-(3,5-dinitrophenyl)carbamoyloxycholan-24-amide (1), N-allyl-N'-methyl-3-(3,5-dinitrophenyl)carbamoyloxy-7,12-bis(2-naphthyl)carbamoyloxycholan-24-amide (2), N-allyl-N'-methyl-3,7-bis(2-naphthyl)carbamoyloxy-12-(3,5-dinitrophenyl)carbamoyloxycholan-24-amide (3), and N-allyl-N'-methyl-3,7,12-tris(2-naphthyl)carbamoyloxycholan-24-amide (4) are presented. To determine the preferred conformations of those chiral auxiliaries, a random search based on the aromatic side-chain conformational degrees of freedom was performed and the energy was minimized using two different molecular mechanics force fields. The low energy structures presenting common features were arranged in groups and selected exploiting appropriate filters. The calculation of theoretical CD spectra according to the De Voe model has allowed a further discrimination among the conformations, specifying which of them gave calculated CD spectra in acceptable agreement with the experimental ones. Finally, taking into account the additivity of the contributions of each 2-naphthylcarbamate chromophore to the CD spectrum of the cholic acid derivatives, and, hence, choosing, for derivatives 1-3, those conformations in which the 2-naphthylcarbamate groups take a similar disposition as in 4, the preferentially assumed conformation of each compound was obtained. A molecular dynamics simulation in the presence of acetonitrile allowed the fluctuations of one of the structures, used as a test case, depending on environmental effects, to be examined.
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Xie, Meimin; Kotecha, Vijay R; Andrade, Jon David P; Fox, James G; Carey, Martin C
2012-01-01
Cholesterol gallstones are associated with slow intestinal transit in humans as well as in animal models, but the molecular mechanism is unknown. We investigated in C57L/J mice whether the components of a lithogenic diet (LD; 1.0% cholesterol, 0.5% cholic acid and 17% triglycerides), as well as distal intestinal infection with Helicobacter hepaticus, influence small intestinal transit time. By quantifying the distribution of 3H-sitostanol along the length of the small intestine following intraduodenal instillation, we observed that, in both sexes, the geometric centre (dimensionless) was retarded significantly (P < 0.05) by LD but not slowed further by helicobacter infection (males, 9.4 ± 0.5 (uninfected), 9.6 ± 0.5 (infected) on LD compared with 12.5 ± 0.4 and 11.4 ± 0.5 on chow). The effect of the LD was reproduced only by the binary combination of cholesterol and cholic acid. We inferred that the LD-induced cholesterol enrichment of the sarcolemmae of intestinal smooth muscle cells produced hypomotility from signal-transduction decoupling of cholecystokinin (CCK), a physiological agonist for small intestinal propulsion in mice. Treatment with ezetimibe in an amount sufficient to block intestinal cholesterol absorption caused small intestinal transit time to return to normal. In most cholesterol gallstone-prone humans, lithogenic bile carries large quantities of hepatic cholesterol into the upper small intestine continuously, thereby reproducing this dietary effect in mice. Intestinal hypomotility promotes cholelithogenesis by augmenting formation of deoxycholate, a pro-lithogenic secondary bile salt, and increasing the fraction of intestinal cholesterol absorbed. PMID:22331417
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Lipidomics Biomarkers of Diet-Induced Hyperlipidemia and Its Treatment with Poria cocos.
Miao, Hua; Zhao, Yu-Hui; Vaziri, Nosratola D; Tang, Dan-Dan; Chen, Hua; Chen, Han; Khazaeli, Mahyar; Tarbiat-Boldaji, Mehrdokht; Hatami, Leili; Zhao, Ying-Yong
2016-02-03
Hyperlipidemia is a major cause of atherosclerotic cardiovascular disease. Poria cocos (PC) is a medicinal product widely used in Asia. This study was undertaken to define the alterations of lipid metabolites in rats fed a high-fat diet to induce hyperlipidemia and to explore efficacy and mechanism of action of PC in the treatment of diet-induced hyperlipidemia. Plasma samples were then analyzed using UPLC-HDMS. The untreated rats fed a high-fat diet exhibited significant elevation of plasma triglyceride and total and low-density lipoprotein (LDL) cholesterol concentrations. This was associated with marked changes in plasma concentrations of seven fatty acids (palmitic acid, hexadecenoic acid, hexanoylcarnitine, tetracosahexaenoic acid, cervonoyl ethanolamide, 3-hydroxytetradecanoic acid, and 5,6-DHET) and five sterols [cholesterol ester (18:2), cholesterol, hydroxytestosterone, 19-hydroxydeoxycorticosterone, and cholic acid]. These changes represented disorders of biosynthesis and metabolism of the primary bile acids, steroids, and fatty acids and mitochondrial fatty acid elongation pathways in diet-induced hyperlipidemia. Treatment with PC resulted in significant improvements of hyperlipidemia and the associated abnormalities of the lipid metabolites.
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NASA Astrophysics Data System (ADS)
Chae, Ari; Park, Soo-Jin; Min, Byunggak; In, Insik
2018-01-01
Facile noncovalent surface functionalization of hydroxylated boron nitride nanosheet (BNNS-OH) was attempted through the sonication-assisted exfoliation of h-BN in aqueous media in the presence of bile acid-based surfactants such as sodium cholic acid (SC) or sodium deoxycholic acid (SDC), resulting in SC- or SDC-BNNS-OH dispersion with high up to 2 mg ml-1 and enhanced dispersion stability due to the increased negative zeta potential. While prepared SC-BNNS-OH revealed multi-layered BNNS structures, the large lateral sizes of hundreds nanometers and clear h-BN lattice structures are very promising for the preparation and application of water-processable BNNS-based nanomaterials. It is regarded that noncovalent functionalization of BNNS-OH based on σ-π interaction between with σ-rich bile acid-based amphiphiles and π-rich BNNS is very effective to formulate multi-functional BNNS-based nanomaterials or hybrids that can be utilized in various applications where both the pristine properties of BNNS and the extra functions are simultaneously required.
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Singh, Manish; Bajaj, Avinash
2014-09-28
We used eight bile acid cationic lipids differing in the number of hydroxyl groups and performed in-depth differential scanning calorimetry studies on model membranes doped with different percentages of these cationic bile acids. These studies revealed that the number and positioning of free hydroxyl groups on bile acids modulate the phase transition and co-operativity of membranes. Lithocholic acid based cationic lipids having no free hydroxyl groups gel well with dipalmitoylphosphatidylcholine (DPPC) membranes. Chenodeoxycholic acid lipids having one free hydroxyl group at the 7'-carbon position disrupt the membranes and lower their co-operativity. Deoxycholic acid and cholic acid based cationic lipids have free hydroxyl groups at the 12'-carbon position, and at 7'- and 12'-carbon positions respectively. Doping of these lipids at high concentrations increases the co-operativity of membranes suggesting that these lipids might induce self-assembly in DPPC membranes. These different modes of interactions between cationic lipids and model membranes would help in future for exploring their use in DNA/drug delivery.
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Mohamed, Mohamed H; Wang, Chen; Peru, Kerry M; Headley, John V; Wilson, Lee D
2017-08-07
Herein, we report on the systematic design and characterization of cross-linked polymer carriers containing β-cyclodextrin (β-CD) and divinyl sulfone (DVS). The polymer carriers were prepared at variable feed ratios (β-CD-DVS; 1:1, 1:2, 1:3, and 1:6) and characterized using spectroscopy (IR, 1 H solution NMR, and 13 C CP-MAS solids NMR spectroscopy), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and a dye decolorization method using phenolphthalein. Uptake studies were carried out at pH 9.00 for the polymer carriers using single component bile acids (cholic acid, deoxycholic acid, glycodeoxycholic acid, and taurodeoxycholic acid). Equilibrium uptake results were evaluated by the Langmuir isotherm model where variable equilibrium parameters were related to the relative apolar character of the bile acid. The Langmuir model yields a carrier/bile acid binding affinity of ∼10 3 M -1 where the lipophilic inclusion sites of the polymer play a prominent role, while the DVS linker framework sites have a lower adsorption affinity, in accordance with the greater hydrophilic character of such sites.
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The role of the gallbladder in humans.
Turumin, J L; Shanturov, V A; Turumina, H E
2013-01-01
The basic function of the gallbladder in humans is one of protection. The accumulation of the primary bile acids (cholic acid and chenodeoxycholic acid) in the gallbladder reduces the formation of the secondary bile acids (deoxycholic acid and lithocholic acid), thus diminishing their concentration in the so-called gallbladder-independent enterohepatic circulation and protecting the liver, the stomach mucosa, the gallbladder, and the colon from their toxic hydrophobic effects. The presence or absence of the gallbladder in mammals is a determining factor in the synthesis of hydrophobic or hydrophilic bile acids. Because the gallbladder contracts 5-20 min after food is in the stomach and the "gastric chyme" moves from the stomach to the duodenum 1-3 h later, the function of the gallbladder bile in digestion may be insignificant. The aim of this article was to provide a detailed review of the role of the gallbladder and the mechanisms related to bile formation in humans. Copyright © 2012 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.
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High-performance functional ecopolymers based on flora and fauna.
Kaneko, Tatsuo
2007-01-01
Liquid crystalline (LC) polymers of rigid monomers based on flora and fauna were prepared by in-bulk polymerization. Para-coumaric (p-coumaric) acid [4-hydroxycinnamic acid (4HCA)] and its derivatives were selected as phytomonomers and bile acids were selected as biomonomers. The 4HCA homopolymer showed a thermotropic LC phase only in a state of low molecular weight. The copolymers of 4HCA with bile acids such as lithocholic acid (LCA) and cholic acid (CA) showed excellent cell compatibilities but low molecular weights. However, P(4HCA-co-CA)s allowed LC spinning to create molecularly oriented biofibers, presumably due to the chain entanglement that occurs during in-bulk chain propagation into hyperbranching architecture. P[4HCA-co-3,4-dihydroxycinnamic acid (DHCA)]s showed high molecular weight, high mechanical strength, high Young's modulus, and high softening temperature, which may be achieved through the entanglement by in-bulk formation of hyperbranching, rigid structures. P(4HCA-co-DHCA)s showed a smooth hydrolysis, in-soil degradation, and photo-tunable hydrolysis. Thus, P(4HCA-co-DHCA)s might be applied as an environmentally degradable plastic with extremely high performance.
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Individual bile acids have differential effects on bile acid signaling in mice
DOE Office of Scientific and Technical Information (OSTI.GOV)
Song, Peizhen, E-mail: songacad@gmail.com; Rockwell, Cheryl E., E-mail: rockwelc@msu.edu; Cui, Julia Yue, E-mail: juliacui@uw.edu
2015-02-15
Bile acids (BAs) are known to regulate BA synthesis and transport by the farnesoid X receptor in the liver (FXR-SHP) and intestine (FXR-Fgf15). However, the relative importance of individual BAs in regulating these processes is not known. Therefore, mice were fed various doses of five individual BAs, including cholic acid (CA), chenodeoxycholic acid (CDCA), deoxoycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) in their diets at various concentrations for one week to increase the concentration of one BA in the enterohepatic circulation. The mRNA of BA synthesis and transporting genes in liver and ileum were quantified. In themore » liver, the mRNA of SHP, which is the prototypical target gene of FXR, increased in mice fed all concentrations of BAs. In the ileum, the mRNA of the intestinal FXR target gene Fgf15 was increased at lower doses and to a higher extent by CA and DCA than by CDCA and LCA. Cyp7a1, the rate-limiting enzyme in BA synthesis, was decreased more by CA and DCA than CDCA and LCA. Cyp8b1, the enzyme that 12-hydroxylates BAs and is thus responsible for the synthesis of CA, was decreased much more by CA and DCA than CDCA and LCA. Surprisingly, neither a decrease in the conjugated BA uptake transporter (Ntcp) nor increase in BA efflux transporter (Bsep) was observed by FXR activation, but an increase in the cholesterol efflux transporter (Abcg5/Abcg8) was observed with FXR activation. Thus in conclusion, CA and DCA are more potent FXR activators than CDCA and LCA when fed to mice, and thus they are more effective in decreasing the expression of the rate limiting gene in BA synthesis Cyp7a1 and the 12-hydroxylation of BAs Cyp8b1, and are also more effective in increasing the expression of Abcg5/Abcg8, which is responsible for biliary cholesterol excretion. However, feeding BAs do not alter the mRNA or protein levels of Ntcp or Bsep, suggesting that the uptake or efflux of BAs is not regulated by FXR at physiological and pharmacological concentrations of BAs. - Highlights: • All four major bile acids in humans activate the FXR in liver and intestine. • These bile acids decreased the mRNA of the bile acid synthetic enzymes Cyp7a1 and Cyp8b1. • These BAs did not alter the mRNA or protein of the conjugated BA transporters (Ntcp and Bsep). • Cholic acid and deoxycholic acid are more potent activators of FXR than chenodeoxycholic acid and lithocholic acid.« less
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Namba, T; Hirota, T; Hayakawa, S
1988-06-01
It has been presumed that ring-A-aromatized bile acids are produced from biliary bile acids by intestinal flora and the acids thus formed participate in the large bowel carcinogenesis. One of these acids is probably 3-hydroxy-19-nor-1,3,5(10)-cholatrien-24-oic acid, judged from the literatures. Consequently, this acid was synthesized from previously prepared 3-methoxy-19-nor-1,3,5(10)-cholatrien-24-ol. The phenolic ether was successively oxidized with pyridinium chlorochromate and wet silver oxide to give 3-methoxy-19-nor-1,3,5(10)-cholatrien-24-oic acid in high yield, which, after successive treatments with methanol containing a catalytic amount of p-toluenesulfonic acid, a combination of aluminum chloride and ethanethiol, and alkali, gave the desired compound in satisfactory yield. The compound was not mutagenic in Salmonella tester strains TA 98 and TA 100, but it increased the mutagenicity of 2-aminoanthracene when both were applied to plates together. When compared with cholic, deoxycholic, and lithocholic acids, the investigated compound exhibited about two to threefold increase of mutagenicity in the latter assay.
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Bai, Guangyue; Wu, Hui; Lou, Pengxiao; Wang, Yujie; Nichifor, Marieta; Zhuo, Kelei; Wang, Jianji; Bastos, Margarida
2017-01-04
Understanding the thermodynamics of formation of biocompatible aggregates is a key factor in the bottom up approach to the development of novel types of drug carriers and their structural tuning using small amphiphilic molecules. We chose an anionic amphiphilic and biocompatible polymer that consists of a dextran and grafted cholic acid pendants, randomly distributed along the dextran backbone, with a degree of substitution (DS) of 15 mol% (designated Dex-15CACOONa). The thermodynamics of interaction and phase behavior of mixtures of this polyelectrolyte and a cationic gemini surfactant hexanediyl-α,ω-bis(dodecyldimethylammonium bromide) (C 12 C 6 C 12 Br 2 ) or its monomer surfactant dodecyltrimethylammonium bromide (DTAB) in aqueous solution were characterized by isothermal titration calorimetry (ITC) and turbidity, together with cryogenic transmission electron microscopy (Cryo-TEM). The various critical concentrations and the enthalpy changes of the corresponding phase transitions for the oppositely charged system were obtained from the plots of the observed enthalpy change (ΔH obs ) and turbidity measurements as a function of gemini concentration. The morphologies of the aggregates in various phases were observed by Cryo-TEM. Altogether these results suggest the critical role of gemini as a dual linker. At the concentrations where the crosslink between the pendant aggregates happens, the free gemini concentration is proximately zero and the aggregate retains its negative charge. The analysis of various factors involved in the interaction allowed a rationalization of the driving forces for mixed aggregate formation, which will contribute to a subsequent rational design of drug delivery systems based on this polymer/surfactant system.
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Liquid crystal based biosensors for bile acid detection
NASA Astrophysics Data System (ADS)
He, Sihui; Liang, Wenlang; Tanner, Colleen; Fang, Jiyu; Wu, Shin-Tson
2013-03-01
The concentration level of bile acids is a useful indicator for early diagnosis of liver diseases. The prevalent measurement method in detecting bile acids is the chromatography coupled with mass spectrometry, which is precise yet expensive. Here we present a biosensor platform based on liquid crystal (LC) films for the detection of cholic acid (CA). This platform has the advantage of low cost, label-free, solution phase detection and simple analysis. In this platform, LC film of 4-Cyano-4'-pentylbiphenyl (5CB) was hosted by a copper grid supported with a polyimide-coated glass substrate. By immersing into sodium dodecyl sulfate (SDS) solution, the LC film was coated with SDS which induced a homeotropic anchoring of 5CB. Addition of CA introduced competitive adsorption between CA and SDS at the interface, triggering a transition from homeotropic to homogeneous anchoring. The detection limit can be tuned by changing the pH value of the solution from 12uM to 170uM.
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Shang, Jing; Liu, Jia; He, Mu; Shang, Erxin; Zhang, Li; Shan, Mingqiu; Yao, Weifeng; Yu, Bing; Yao, Yingzhi; Ding, Anwei
2014-04-01
Blood heat and hemorrhage (BHH) syndrome is the most common bleeding disease in clinic. In this study, a rat model with BHH syndrome was built for the first time. Biochemical study showed the intrinsic coagulation pathways and the platelet aggregation rate in the rat model were inhibited, while extrinsic pathway of coagulation cascade was activated. An UHPLC/Q-TOF MS combined with orthogonal partial least squares-discriminant analysis (OPLS-DA) was employed to construct plasma metabolic profiling of the rat model with BHH syndrome. Twenty-four unique metabolites were identified, which were involved in glycerophospholipid metabolism, arachidonic acid metabolism, fatty acid metabolism, amino acid metabolism and cholic acid metabolism. In the end, we concluded that bleeding mechanism of the rat with BHH syndrome may be associated with augmenting blood viscosity, inhibiting platelet aggregation and intrinsic coagulation pathways. Copyright © 2013 Elsevier B.V. All rights reserved.
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Yan, Shi-Kai; Wu, Yan-Wen; Liu, Run-Hui; Zhang, Wei-Dong
2007-01-01
Major bioactive components in various Calculus Bovis, including natural, artificial and in-vitro cultured Calculus Bovis, were comparatively studied. An approach of high-performance liquid chromatography coupled with ultraviolet and evaporative light scattering detections (HPLC/UV/ELSD) was established to simultaneously determinate six bioactive components thereof, including five bile acids (cholic acid, deoxycholic acid, ursodeoxycholic, chenodeoxycholic acid, hyodeoxycholic acid) and bilirubin. ELSD and UV detector were applied to detect bile acids and bilirubin respectively. The assay was performed on a C(18) column with water-acetonitrile gradient elution and the investigated constituents were authenticated by comparing retention times and mass spectra with those of reference compounds. The proposed method was applied to analyze twenty-one Calculus Bovis extraction samples, and produced data with acceptable linearity, precision, repeatability and accuracy. The result indicated the variations among Calculus Bovis samples under different developmental conditions. Artificial and in-vitro cultured Calculus Bovis, especially in-vitro cultured ones, which contain total bioactive constituents no less than natural products and have the best batch-to-batch uniformity, suffice to be used as substitutes of natural Calculus Bovis.
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Wang, Haina; Fang, Zhong-Ze; Meng, Ran; Cao, Yun-Feng; Tanaka, Naoki; Krausz, Kristopher W; Gonzalez, Frank J
2017-07-01
Alpha-naphthyl isothiocyanate (ANIT) is a common hepatotoxicant experimentally used to reproduce the pathologies of drug-induced liver injury in humans, but the mechanism of its toxicity remains unclear. To determine the metabolic alterations following ANIT exposure, metabolomic analyses was performed by use of liquid chromatography-mass spectrometry. Partial least squares discriminant analysis (PLS-DA) of liver, serum, bile, ileum, and cecum of vehicle- and ANIT-treated mice revealed significant alterations of individual bile acids, including increased tauroursodeoxycholic acid, taurohydrodeoxycholic acid, taurochenodeoxycholic acid, and taurodeoxycholic acid, and decreased ω-, β- and tauro-α/β- murideoxycholic acid, cholic acid, and taurocholic acid in the ANIT-treated groups. In accordance with these changes, ANIT treatment altered the expression of mRNAs encoded by genes responsible for the metabolism and transport of bile acids and cholesterol. Pre-treatment of glycyrrhizin (GL) and glycyrrhetinic acid (GA) prevented ANIT-induced liver damage and reversed the alteration of bile acid metabolites and Cyp7a1, Npc1l1, Mttp, and Acat2 mRNAs encoding bile acid transport and metabolism proteins. These results suggested that GL/GA could prevent drug-induced liver injury and ensuing disruption of bile acid metabolism in humans. Published by Elsevier B.V.
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Scheurlen, C; Kruis, W; Büll, U; Stellaard, F; Lang, P; Paumgartner, G
1986-01-01
Measurement of the retention of 23-75Se-25-homotaurocholic acid (SeHCAT) has been suggested as a new test for ileal function. We investigated 31 patients with chronic diarrhea, 10 with ileal Crohn's disease and 21 with diarrhea but without ileal disease. The whole-body retention half-life of 1 mu Ci SeHCAT was determined and compared to the fecal content of total and individual bile acids. Patients with ileal disease had increased primary fecal bile acids (chenodeoxycholic acid: mean 6.95 mg/g dry weight, range 3.15-10.6 mg/g; cholic acid: mean 18.15 mg/g, range 10.3-33.9 mg/g) and a short SeHCAT retention (mean 11.9 h, range 2-24 h), whereas patients with intact ileum had normal fecal bile acids and a SeHCAT retention of 85.9 h (range 28-216 h). SeHCAT retention half-life differentiated well between patients with ileal disease and patients with normal ileum, thus indicating the SeHCAT test as a valid investigation method for detection of primary bile acid malabsorption in patients with chronic diarrhea and ileal dysfunction.
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2015-01-01
A novel trifluorinated cholic acid derivative, CA-lys-TFA, was designed and synthesized for use as a tool to measure bile acid transport noninvasively using magnetic resonance imaging (MRI). In the present study, the in vivo performance of CA-lys-TFA for measuring bile acid transport by MRI was investigated in mice. Gallbladder CA-lys-TFA content was quantified using MRI and liquid chromatography/tandem mass spectrometry. Results in wild-type (WT) C57BL/6J mice were compared to those in mice lacking expression of Asbt, the ileal bile acid transporter. 19F signals emanating from the gallbladders of WT mice 7 h after oral gavage with 150 mg/kg CA-lys-TFA were reproducibly detected by MRI. Asbt-deficient mice administered the same dose had undetectable 19F signals by MRI, and gallbladder bile CA-lys-TFA levels were 30-fold lower compared to WT animals. To our knowledge, this represents the first report of in vivo imaging of an orally absorbed drug using 19F MRI. Fluorinated bile acid analogues have potential as tools to measure and detect abnormal bile acid transport by MRI. PMID:24708306
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Poša, Mihalj; Pilipović, Ana; Bećarević, Mirjana; Farkaš, Zita
2017-01-01
Due to a relatively small size of bile acid salts, their mixed micelles with nonionic surfactants are analysed. Of the special interests are real binary mixed micelles that are thermodynamically more stable than ideal mixed micelles. Thermodynamic stability is expressed with an excess Gibbs energy (G E ) or over an interaction parameter (β ij ). In this paper sodium salts of cholic (C) and hyodeoxycholic acid (HD) in their mixed micelles with Tween 40 (T40) are analysed by potentiometric titration and their pKa values are determined. Examined bile acids in mixed micelles with T40 have higher pKa values than free bile acids. The increase of ΔpKa acid constant of micellary bound C and HD is in a correlation with absolute values of an interaction parameter. According to an interaction parameter and an excess Gibbs energy, mixed micelle HD-T40 are thermodynamically more stable than mixed micelles C-T40. ΔpKa values are higher for mixed micelles with Tween 40 whose second building unit is HD, related to the building unit C. In both micellar systems, ΔpKa increases with the rise of a molar fraction of Tween 40 in binary mixtures of surfactants with sodium salts of bile acids. This suggests that, ΔpKa can be a measure of a thermodynamic stabilization of analysed binary mixed micelles as well as an interaction parameter. ΔpKa values are confirmed by determination of a distribution coefficient of HD and C in systems: water phase with Tween 40 in a micellar concentration and 1-octanol, with a change of a pH value of a water phase. Conformational analyses suggests that synergistic interactions between building units of analysed binary micelles originates from formation of hydrogen bonds between steroid OH groups and polyoxyethylene groups of the T40. Relative similarity and spatial orientation of C 3 and C 6 OH group allows cooperative formation of hydrogen bonds between T40 and HD - excess entropy in formation of mixed micelle. If a water solution of analysed binary mixtures of surfactants contains urea in concentration of 4M significant decreases of an interaction parameter value happens which confirms the importance of hydrogen bonds in synergistic interactions (urea compete in hydrogen bonds). Copyright © 2016 Elsevier Inc. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Beck, R.N.; Cooper, M.C.
1982-06-01
This 3-y report cites progress in the following areas of radiopharmaceutical research: cyclotron operations; /sup 51/Mn for myocardial localization; /sup 82/Rb for heart imaging; /sup 15/O-labelled H/sub 2/O and molecular oxygen; studies on /sup 11/C-2-deoxyglucose localization; /sup 13/NH/sub 3/ measurements of myocardial perfusion; /sup 130/Cs myocardial imaging; heart motion studies; labelled amino acids for pancreatic imaging; /sup 11/C-hexamethonium for cartilage imaging; /sup 11/C-cholic acid pharmacology; blood element labelling with /sup 115m/In; /sup 75/Br studies; extrapolation of animal data to humans; in vivo quantification of radioactivity; fetal and neonatal radiation effects from radiopharmaceuticals administered to pregnant and lactating mice; and verificationmore » of MIRD absorbed dose calculations for some organ-incorporated radionuclides. (ERB)« less
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Genetic and biochemical characterization of periplasmic-leaky mutants of Escherichia coli K-12.
Lazzaroni, J C; Portalier, R C
1981-01-01
Periplasmic-leaky mutants of Escherichia coli K-12 were isolated after nitrosoguanidine-induced mutagenesis. They released periplasmic enzymes into the extracellular medium. Excretion of alkaline phosphatase, which started immediately in the early exponential phase of growth, could reach up to 90% of the total enzyme production in the stationary phase. Leaky mutants were sensitive to ethylenediaminetetraacetic acid, cholic acid, and the antibiotics rifampin, chloramphenicol, mitomycin C, and ampicillin. Furthermore, they were resistant to colicin E1 and partially resistant to phage TuLa. Their genetic characterization showed that the lky mutations mapped between the suc and gal markers, near or in the tolPAB locus. A biochemical analysis of cell envelope components showed that periplasmic-leaky mutants contained reduced amounts of major outer membrane protein OmpF and increased amounts of a 16,000-dalton outer membrane protein. Images PMID:7009581
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FXR signaling in the enterohepatic system
Matsubara, Tsutomu; Li, Fei; Gonzalez, Frank J.
2012-01-01
Enterohepatic circulation serves to capture bile acids and other steroid metabolites produced in the liver and secreted to the intestine, for reabsorption back into the circulation and reuptake to the liver. This process is under tight regulation by nuclear receptor signaling. Bile acids, produced from cholesterol, can alter gene expression in the liver and small intestine via activating the nuclear receptors farnesoid X receptor (FXR; NR1H4), pregnane X receptor (PXR; NR1I2), vitamin D receptor (VDR; NR1I1), G protein coupled receptor TGR5, and other cell signaling pathways (JNK1/2, AKT and ERK1/2). Among these controls, FXR is known to be a major bile acid-responsive ligand-activated transcription factor and a crucial control element for maintaining bile acid homeostasis. FXR has a high affinity for several major endogenous bile acids, notably cholic acid, deoxycholic acid, chenodeoxycholic acid, and lithocholic acid. By responding to excess bile acids, FXR is a bridge between the liver and small intestine to control bile acid levels and regulate bile acid synthesis and enterohepatic flow. FXR is highly expressed in the liver and gut, relative to other tissues, and contributes to the maintenance of cholesterol/bile acid homeostasis by regulating a variety of metabolic enzymes and transporters. FXR activation also affects lipid and glucose metabolism, and can influence drug metabolism. PMID:22609541
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Hu, Peng-Li; Yuan, Ya-Hong; Yue, Tian-Li
2018-01-01
This study aimed to analyze the bile acid patterns in commercially available oxgall powders used for evaluation of the bile tolerance ability of probiotic bacteria. Qxgall powders purchased from Sigma-Aldrich, Oxoid and BD Difco were dissolved in distilled water, and analyzed. Conjugated bile acids were profiled by ion-pair high-performance liquid chromatography (HPLC), free bile acids were detected as their p-bromophenacyl ester derivatives using reversed-phase HPLC after extraction with acetic ether, and total bile acids were analyzed by enzymatic-colorimetric assay. The results showed that 9 individual bile acids (i.e., taurocholic acid, glycocholic acid, taurodeoxycholic acid, glycodeoxycholic acid, taurochenodeoxycholic acid, glycochenodeoxycholic acid, cholic acid, chenodeoxycholic acid, deoxycholic acid) were present in each of the oxgall powders tested. The content of total bile acid among the three oxgall powders was similar; however, the relative contents of the individual bile acids among these oxgall powders were significantly different (P < 0.001). The oxgall powder from Sigma-Aldrich was closer to human bile in the ratios of glycine-conjugated bile acids to taurine-conjugated bile acids, dihydroxy bile acids to trihydroxy bile acids, and free bile acids to conjugated bile acids than the other powders were. It was concluded that the oxgall powder from Sigma-Aldrich should be used instead of those from Oxoid and BD Difco to evaluate the bile tolerance ability of probiotic bacteria as human bile model. PMID:29494656
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Lu, Li Ping; Wan, Yan Ping; Xun, Peng Cheng; Zhou, Ke Jun; Chen, Cheng; Cheng, Si Yang; Zhang, Min Zhong; Wu, Chun Hua; Lin, Wei Wei; Jiang, Ying; Feng, Hai Xia; Wang, Jia Lu; He, Ka; Cai, Wei
2017-08-01
To determine serum bile acid (BA) and fatty acid (FA) profiles in Chinese children with non-alcoholic fatty liver disease (NAFLD). A total 76 children aged 4-17 years were categorized into three groups according to the presence and absence of as well as the severity of NAFLD, that is, non-NAFLD (control), mild and moderate to severe NAFLD groups, respectively, based on their liver ultrasonography findings. Serum BA and FA profiles were quantified separately by mass spectrometry and gas chromatography. General linear models were performed to assess the differences among the groups. After adjusted for potential confounders, children with NAFLD had higher levels of chenodeoxycholic acid (CDCA), unconjugated primary BAs (CDCA + cholic acid) but lower levels of deoxycholic acid (DCA), taurodeoxycholic acid (TDCA), glycodeoxycholic acid (GDCA), total DCA (DCA + TDCA + GDCA), glycolithocholic acid (GLCA) and total lithocholic acid (GLCA + taurolithocholic acid) than children without NAFLD. As for FAs, children with mild and moderate to severe NAFLD had higher levels of n-7 monounsaturated FA. Circulating BA and FA profiles may change in children with NAFLD. Further studies are needed to determine their associations and to understand the underlying mechanism of action. © 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.
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Tsuchiya, Hiroyuki; da Costa, Kerry-Ann; Lee, Sangmin; Renga, Barbara; Jaeschke, Hartmut; Yang, Zhihong; Orena, Stephen J; Goedken, Michael J; Zhang, Yuxia; Kong, Bo; Lebofsky, Margitta; Rudraiah, Swetha; Smalling, Rana; Guo, Grace; Fiorucci, Stefano; Zeisel, Steven H; Wang, Li
2015-05-01
Hyperhomocysteinemia is often associated with liver and metabolic diseases. We studied nuclear receptors that mediate oscillatory control of homocysteine homeostasis in mice. We studied mice with disruptions in Nr0b2 (called small heterodimer partner [SHP]-null mice), betaine-homocysteine S-methyltransferase (Bhmt), or both genes (BHMT-null/SHP-null mice), along with mice with wild-type copies of these genes (controls). Hyperhomocysteinemia was induced by feeding mice alcohol (National Institute on Alcohol Abuse and Alcoholism binge model) or chow diets along with water containing 0.18% DL-homocysteine. Some mice were placed on diets containing cholic acid (1%) or cholestyramine (2%) or high-fat diets (60%). Serum and livers were collected during a 24-hour light-dark cycle and analyzed by RNA-seq, metabolomic, and quantitative polymerase chain reaction, immunoblot, and chromatin immunoprecipitation assays. SHP-null mice had altered timing in expression of genes that regulate homocysteine metabolism compared with control mice. Oscillatory production of S-adenosylmethionine, betaine, choline, phosphocholine, glyceophosphocholine, cystathionine, cysteine, hydrogen sulfide, glutathione disulfide, and glutathione, differed between SHP-null mice and control mice. SHP inhibited transcriptional activation of Bhmt and cystathionine γ-lyase by FOXA1. Expression of Bhmt and cystathionine γ-lyase was decreased when mice were fed cholic acid but increased when they were placed on diets containing cholestyramine or high-fat content. Diets containing ethanol or homocysteine induced hyperhomocysteinemia and glucose intolerance in control, but not SHP-null, mice. In BHMT-null and BHMT-null/SHP-null mice fed a control liquid, lipid vacuoles were observed in livers. Ethanol feeding induced accumulation of macrovesicular lipid vacuoles to the greatest extent in BHMT-null and BHMT-null/SHP-null mice. Disruption of Shp in mice alters timing of expression of genes that regulate homocysteine metabolism and the liver responses to ethanol and homocysteine. SHP inhibits the transcriptional activation of Bhmt and cystathionine γ-lyase by FOXA1. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
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NASA Astrophysics Data System (ADS)
Pan, Amy; Zhang, Hongyong; Li, Yuanpei; Lin, Tzu-yin; Wang, Fuli; Lee, Joyce; Cheng, Mingshan; Dall'Era, Marc; Li, Tianhong; deVere White, Ralph; Pan, Chong-Xian; Lam, Kit S.
2016-10-01
Chemotherapy commonly used in the treatment of advanced bladder cancer is only moderately effective and associated with significant toxicity. There has been no appreciable improvement in overall survival over the last three decades. The goal of this project is to develop and characterize bladder cancer-specific nanometer-scale micelles loaded with the chemotherapeutic drug paclitaxel (PTX) and determine the anti-tumor activity and toxicity. Micelle-building-material telodendrimers were synthesized through the stepwise conjugation of eight cholic acid units at one terminus of polyethylene glycol (PEG) and a bladder cancer-specific targeting peptide named PLZ4 at the other terminus. To synthesize disulfide-crosslinked PLZ4 nanomicelles (DC-PNM), cysteine was introduced between the cholic acid and PEG. DC-PNM-PTX was synthesized through the evaporation method by loading PTX in the core. The loading capacity of PTX in DC-PNM was 25% (W/W). The loading efficiency was over 99%. DC-PNM-PTX was spherical with the median size of 25 nm. The stability of DC-PNM-PTX was determined in a solution containing sodium docecyl sulfate (SDS). It was stable in a SDS solution, but dissolved within 5 min after the addition of glutathione at the physiological intracellular concentration of 10 mM. In vivo targeting and anti-tumor activity were determined in immunodeficient mice carrying patient-derived bladder cancer xenografts (PDXs). After intravenous administration, DC-PNM specifically targeted the bladder cancer PDXs, but very little to the lung cancer xenografts in the same mice (p < 0.001). DC-PNM loaded with PTX overcame cisplatin resistance, and improved the median survival from 55 d with free PTX to 69.5 d (p = 0.03) of mice carrying PDXs. In conclusion, DC-PNM remained stable in the SDS solution, specifically targeted the bladder cancer xenografts in vivo, and improved the anti-cancer efficacy of PTX.
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Yañez, Fernando; Chianella, Iva; Piletsky, Sergey A; Concheiro, Angel; Alvarez-Lorenzo, Carmen
2010-02-05
This work has focused on the rational development of polymers capable of acting as traps of bile salts. Computational modeling was combined with molecular imprinting technology to obtain networks with high affinity for cholate salts in aqueous medium. The screening of a virtual library of 18 monomers, which are commonly used for imprinted networks, identified N-(3-aminopropyl)-methacrylate hydrochloride (APMA.HCl), N,N-diethylamino ethyl methacrylate (DEAEM) and ethyleneglycol methacrylate phosphate (EGMP) as suitable functional monomers with medium-to-high affinity for cholic acid. The polymers were prepared with a fix cholic acid:functional monomer mole ratio of 1:4, but with various cross-linking densities. Compared to polymers prepared without functional monomer, both imprinted and non-imprinted microparticles showed a high capability to remove sodium cholate from aqueous medium. High affinity APMA-based particles even resembled the performance of commercially available cholesterol-lowering granules. The imprinting effect was evident in most of the networks prepared, showing that computational modeling and molecular imprinting can act synergistically to improve the performance of certain polymers. Nevertheless, both the imprinted and non-imprinted networks prepared with the best monomer (APMA.HCl) identified by the modeling demonstrated such high affinity for the template that the imprinting effect was less important. The fitting of adsorption isotherms to the Freundlich model indicated that, in general, imprinting increases the population of high affinity binding sites, except when the affinity of the functional monomer for the target molecule is already very high. The cross-linking density was confirmed as a key parameter that determines the accessibility of the binding points to sodium cholate. Materials prepared with 9% mol APMA and 91% mol cross-linker showed enough affinity to achieve binding levels of up to 0.4 mmol g(-1) (i.e., 170 mg g(-1)) under flow (1 mL min(-1)) of 0.2 mM sodium cholate solution. Copyright 2009 Elsevier B.V. All rights reserved.
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Olfactory transduction pathways in the Senegalese sole Solea senegalensis.
Velez, Z; Hubbard, P C; Barata, E N; Canário, A V M
2013-09-01
This study tested whether differences in sensitivity between the upper and lower olfactory epithelia of Solea senegalensis are associated with different odorant receptors and transduction pathways, using the electro-olfactogram. Receptor mechanisms were assessed by cross-adaptation with amino acids (L-cysteine, L-phenylalanine and 1-methyl-L-tryptophan) and bile acids (taurocholic acid and cholic acid). This suggested that relatively specific receptors exist for 1-methyl-L-tryptophan and L-phenylalanine (food-related odorants) in the lower epithelium, and for taurocholic acid (conspecific-derived odorant) in the upper. Inhibition by U73122 [a phospholipase C (PLC) inhibitor] suggested that olfactory responses to amino acids were mediated mostly, but not entirely, by PLC-mediated transduction (IC50 ; 15-55 nM), whereas bile acid responses were mediated by both PLC and adenylate cyclase-cyclic adenosine monophosphate (AC-cAMP) (using SQ-22536; an AC inhibitor). Simultaneous application of both drugs rarely inhibited responses completely, suggesting possible involvement of non-PLC and non-AC mediated mechanisms. For aromatic amino acids and bile acids, there were differences in the contribution of each transduction pathway (PLC, AC and non-PLC and non-AC) between the two epithelia. These results suggest that differences in sensitivity of the two epithelia are associated with differences in odorant receptors and transduction mechanisms. © 2013 The Fisheries Society of the British Isles.
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Hypersecretion of mucus glycoprotein by the gallbladder epithelium in experimental cholelithiasis.
Lee, S P
1981-07-01
In three models of cholelithiasis (dihydrocholesterol-fed rabbits, cholesterol-cholic acid-fed mice, and Lincomycin-treated guinea pigs), the quantity and chemical composition of gallbladder epithelial mucin have been studied using (1) a spectrum of histochemical glycoprotein stains, and (2) biochemical extraction, purification and analysis of the carbohydrate components of epithelial mucin. Despite the diverse mechanism of stone induction and difference in stone composition, a common pattern of response by the epithelial mucin was observed in all three models. There was a quantitative increase in epithelial mucus production at a time before stones were formed and this increase persisted till stones were formed. There was no difference, qualitatively, between mucus produced by normal and stone-forming gallbladders.
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Huerta-Ángeles, Gloria; Brandejsová, Martina; Novotný, Jaroslav; Kopecká, Kateřina; Šógorková, Jana; Šmejkalová, Daniela; Velebný, Vladimír
2018-08-01
In this work, amphiphilic hyaluronic acid (HA) was synthesized by the chemical bonding of steroids. Particularly, succinyl cholesterol (SCH), cholic acid (CA), deoxycholic acid (DOCA), and 18β-glycyrrhetinic acid (GA) were activated by benzoyl chloride towards the esterification reaction of HA in water. The degree of substitution can be controlled by varying the feed ratio of mixed anhydride to HA and up to 25% (mol/mol) can be obtained. Due to mild reaction conditions, no degradation of the polysaccharide was observed. The prepared amphiphilic polymers were characterized by NMR, infrared spectroscopy (FT-IR) and SEC/MALLS, as well as turbidity and size of the aggregates. The developed system is proposed for the delivery of hydrophobic drugs; for this purpose, curcumin, vitamin E and coenzyme Q10 were used as hydrophobic models; these molecules were loaded into the conjugates with high efficiency. The loading capacity was a function of degree of substitution. Furthermore, the biocompatibility of the derivatives and the cellular uptake of the delivery system enabled us to demonstrate the potential of the prepared delivery systems. Copyright © 2018 Elsevier Ltd. All rights reserved.
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Singh, Namrata; Bhattacharyya, Debasish
2016-04-15
An ether extract of nine different bacterial metabolites in combination with two solvent extract (ether followed by ethanol) of bile lipids from ox gall bladder is used as an immune stimulator drug. Over the years bile acids are discussed regarding their anti-oxidant and lipid peroxidation properties. Since some of the bile acids are known to be potent antioxidants, presence of similar activity in the solvent extract of ox bile lipid was investigated using TLC and reverse phase HPLC systems. Fractions from HPLC were analyzed with mass spectrometry using electrospray ionization. The presence of twelve different bile acids along with other substances in small proportions including fatty acids, sulfate conjugates and bile pigments were confirmed. The twelve separated peaks had similar retention times as those of tauroursodeoxycholic acid, glycoursodeoxycholic acid, taurocholic acid, glycocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, cholic acid, ursodeoxycholic acid, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid. Subsequently, all fractions were tested for their anti-oxidative property on HepG2 cells exposed to H2O2 that served as an oxidative injury model. Four fluorescent dyes H2DCF DA, MitoSOX red, Amplex red and DAF-2 DA were used for estimation of reactive radicals in the HepG2 cells. Among the separated bile acids, tauroursodeoxycholic acid, glycoursodeoxycholic acid and ursodeoxycholic acid prevented the HepG2 cells from H2O2-induced oxidative stress. Copyright © 2015 Elsevier B.V. All rights reserved.
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Nakasone, Noboru; Toma, Claudia; Higa, Naomi; Koizumi, Yukiko; Ogura, Yasunori; Suzuki, Toshihiko
2011-02-01
The effects of detergents (cholic acid, deoxycholic acid, Triton X-100, and Nonidet P-40) on the secretion of EspB from the locus for enterocyte effacement (LEE) gene-positive Escherichia coli strains were examined. Clinical isolates of eight EPEC strains and seven STEC strains were used to detect EspB after they had been cultivated in Luria-Bertani (LB) broth containing one of the detergents. When the bacteria were cultured in LB broth supplemented with one of the detergents, the amount of EspB produced was increased by 2-32-fold depending on the detergent and the strain used. EspB was detected in all strains when they were cultured in LB broth containing all of the detergents. The results obtained in this study can be applied to immunological diagnostic methods for detecting EspB and also to the production of EspB for research purposes. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
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Sciarretta, G; Furno, A; Morrone, B; Malaguti, P
1994-07-01
Chronic diarrhea of unknown origin is often associated with bile acid malabsorption, the pathogenetic role of which is uncertain. The aim of this study was to identify morphological abnormalities in the ileal and colonic mucosa in patients with this disorder. We performed a prospective and blinded histopathological study (between June 1991 and November 1992) of endoscopic biopsies of the distal ileum and colon of 23 patients suffering from chronic diarrhea of unknown origin. In 14, the SeHCAT (75-selena-homo-cholic acid taurine) test was abnormal owing to bile acid malabsorption; in the other nine, the diarrhea control group, the test results were normal. A detailed evaluation of surface epithelium, immune response and inflammatory changes was made. in two patients and two controls, mild villous atrophy was observed; there was also slight inflammation of the ileal and colonic mucosa occurring with the same frequency in both groups. A slight replacement of goblet cells was more evident in the diarrhea control group. Chronic diarrhea of unknown origin associated with bile acid malabsorption does not involve specific morphological changes of ileal or colonic mucosa, and its pathogenesis must be looked for in dysfunction of the ileum and/or colon.
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Chayrov, Radoslav L; Stylos, Evgenios K; Chatziathanasiadou, Maria V; Chuchkov, Kiril N; Tencheva, Aleksandra I; Kostagianni, Androniki D; Milkova, Tsenka S; Angelova, Assia L; Galabov, Angel S; Shishkov, Stoyan A; Todorov, Daniel G; Tzakos, Andreas G; Stankova, Ivanka G
2018-05-19
Bile acid prodrugs have served as a viable strategy for refining the pharmaceutical profile of parent drugs through utilizing bile acid transporters. A series of three ester prodrugs of the antiherpetic drug acyclovir (ACV) with the bile acids cholic, chenodeoxycholic and deoxycholic were synthesized and evaluated along with valacyclovir for their in vitro antiviral activity against herpes simplex viruses type 1 and type 2 (HSV-1, HSV-2). The in vitro antiviral activity of the three bile acid prodrugs was also evaluated against Epstein-Barr virus (EBV). Plasma stability assays, utilizing ultra-high performance liquid chromatography coupled with tandem mass spectrometry, in vitro cytotoxicity and inhibitory experiments were conducted in order to establish the biological profile of ACV prodrugs. The antiviral assays demonstrated that ACV-cholate had slightly better antiviral activity than ACV against HSV-1, while it presented an eight-fold higher activity with respect to ACV against HSV-2. ACV-chenodeoxycholate presented a six-fold higher antiviral activity against HSV-2 with respect to ACV. Concerning EBV, the highest antiviral effect was demonstrated by ACV-chenodeoxycholate. Human plasma stability assays revealed that ACV-deoxycholate was more stable than the other two prodrugs. These results suggest that decorating the core structure of ACV with bile acids could deliver prodrugs with amplified antiviral activity.
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Festi, D.; Capodicasa, S.; Sandri, L.; Colaiocco-Ferrante, L.; Staniscia, T.; Vitacolonna, E.; Vestito, A.; Simoni, P.; Mazzella, G.; Portincasa, P.; Roda, E.; Colecchia, A.
2005-01-01
AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels. METHODS: One hundred and forty patients (50 HCV- related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated. RESULTS: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids. Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test. CONCLUSION: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients. PMID:15609414
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Raja, Boobalan; Saravanakumar, Murugesan; Sathya, Gopal
2012-07-01
An investigation was made to reveal the protective effects of veratric acid (VA), a phenolic acid against atherogenic diet-induced hyperlipidemic rats. Male albino Wistar rats were fed with atherogenic diet (4% cholesterol, 1% cholic acid, and 0.5% 2-thiouracil) daily for 30 days and treated with VA (40 mg/kg body weight) daily for a period of 30 days. Rats fed with atherogenic diet showed significant (P < 0.05) elevation in the level of plasma lipids, systolic and diastolic blood pressure, oxidative stress markers (thiobarbituric acid reactive substances, lipid peroxides) and significant (P < 0.05) reduction in the activities of enzymatic (superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic (vitamin C, vitamin E, and reduced glutathione) antioxidants in erythrocytes, plasma, and tissues (liver, kidney, and aorta). Oral administration of VA (40 mg/kg body weight) for 30 days to atherogenic diet fed rats markedly attenuates systolic, diastolic blood pressure and lipid peroxidation products. Further, VA treatment significantly improved enzymatic and non-enzymatic antioxidants levels and showed beneficial effects on lipid profile in atherogenic diet rats. All the above alterations were supported by histopathological observations. These results indicate that oral administration of VA ameliorates atherogenic diet-induced hyperlipidemia in rats by its free radical scavenging; improving the antioxidants and lipid lowering properties.
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Mitamura, Kuniko; Hori, Naohiro; Mino, Shiori; Iida, Takashi; Hofmann, Alan F; Ikegawa, Shigeo
2012-04-01
The 3-sulfates of the S-acyl glutathione (GSH) conjugates of five natural bile acids (cholic, chenodeoxycholic, deoxycholic, ursodeoxycholic, and lithocholic) were synthesized as reference standards in order to investigate their possible formation by a rat liver cytosolic fraction. Their structures were confirmed by proton nuclear magnetic resonance, as well as by means of electrospray ionization-linear ion-trap mass spectrometry with negative-ion detection. Upon collision-induced dissociation, structurally informative product ions were observed. Using a triple-stage quadrupole instrument, selected reaction monitoring analyses by monitoring characteristic transition ions allowed the achievement of a highly sensitive and specific assay. This method was used to determine whether the 3-sulfates of the bile acid-GSH conjugates (BA-GSH) were formed when BA-GSH were incubated with a rat liver cytosolic fraction to which 3'-phosphoadenosine 5'-phosphosulfate had been added. The S-acyl linkage was rapidly hydrolyzed to form the unconjugated bile acid. A little sulfation of the GSH conjugates occurred, but greater sulfation at C-3 of the liberated bile acid occurred. Sulfation was proportional to the hydrophobicity of the unconjugated bile acid. Thus GSH conjugates of bile acids as well as their C-3 sulfates if formed in vivo are rapidly hydrolyzed by cytosolic enzymes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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Feng, Lu; Yuen, Yee-Lok; Xu, Jian; Liu, Xing; Chan, Martin Yan-Chun; Wang, Kai; Fong, Wing-Ping; Cheung, Wing-Tai; Lee, Susanna Sau-Tuen
2017-01-01
PPARα has been known to play a pivotal role in orchestrating lipid, glucose, and amino acid metabolism via transcriptional regulation of its target gene expression during energy deprivation. Recent evidence has also suggested that PPARα is involved in bile acid metabolism, but how PPARα modulates the homeostasis of bile acids during fasting is still not clear. In a mechanistic study aiming to dissect the spectrum of PPARα target genes involved in metabolic response to fasting, we identified a novel mouse gene (herein named mL-STL for mouse liver-sulfotransferase-like) that shared extensive homology with the Sult2a subfamily of a superfamily of cytosolic sulfotransferases, implying its potential function in sulfonation. The mL-STL gene expressed predominantly in liver in fed state, but PPARα was required to sustain its expression during fasting, suggesting a critical role of PPARα in regulating the mL-STL-mediated sulfonation during fasting. Functional studies using recombinant His-tagged mL-STL protein revealed its narrow sulfonating activities toward 7α-hydroxyl primary bile acids, including cholic acid, chenodeoxycholic acid, and α-muricholic acid, and thus suggesting that mL-STL may be the major hepatic bile acid sulfonating enzyme in mice. Together, these studies identified a novel PPARα-dependent gene and uncovered a new role of PPARα as being an essential regulator in bile acid biotransformation via sulfonation during fasting. PMID:28442498
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Fujita, Kyosuke; Iguchi, Yusuke; Une, Mizuho; Watanabe, Shiro
2017-04-01
The farnesoid X receptor (FXR) is a major nuclear receptor of bile acids; its activation suppresses sterol regulatory element-binding protein 1c (SREBP1c)-mediated lipogenesis and decreases the lipid contents in the liver. There are many reports showing that the administration of ursodeoxycholic acid (UDCA) suppresses lipogenesis and reduces the lipid contents in the liver of experimental animals. Since UDCA is not recognized as an FXR agonist, these effects of UDCA cannot be readily explained by its direct activation of FXR. We observed that the dietary administration of UDCA in mice decreased the expression levels of SREBP1c and its target lipogenic genes. Alpha- and β-muricholic acids (MCA) and cholic acid (CA) were the major bile acids in the mouse liver but their contents decreased upon UDCA administration. The hepatic contents of chenodeoxycholic acid and deoxycholic acid (DCA) were relatively low but were not changed by UDCA. UDCA did not show FXR agonistic or antagonistic potency in in vitro FXR transactivation assay. Taking these together, we deduced that the above-mentioned change in hepatic bile acid composition induced upon UDCA administration might cause the relative increase in the FXR activity in the liver, mainly by the reduction in the content of β-MCA, a farnesoid X receptor antagonist, which suggests a mechanism by which UDCA suppresses lipogenesis and decreases the lipid contents in the mouse liver.
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Poša, Mihalj; Tepavčević, Vesna
2011-09-01
The formation of mixed micelles built of 7,12-dioxolithocholic and the following hydrophobic bile acids was examined by conductometric method: cholic (C), deoxycholic (D), chenodeoxycholic (CD), 12-oxolithocholic (12-oxoL), 7-oxolithocholic (7-oxoL), ursodeoxycholic (UD) and hiodeoxycholic (HD). Interaction parameter (β) in the studied binary mixed micelles had negative value, suggesting synergism between micelle building units. Based on β value, the hydrophobic bile acids formed two groups: group I (C, D and CD) and group II (12-oxoL, 7-oxoL, UD and HD). Bile acids from group II had more negative β values than bile acids from group I. Also, bile acids from group II formed intermolecular hydrogen bonds in aggregates with both smaller (2) and higher (4) aggregation numbers, according to the analysis of their stereochemical (conformational) structures and possible structures of mixed micelles built of these bile acids and 7,12-dioxolithocholic acid. Haemolytic potential and partition coefficient of nitrazepam were higher in mixed micelles built of the more hydrophobic bile acids (C, D, CD) and 7,12-dioxolithocholic acid than in micelles built only of 7,12-dioxolithocholic acid. On the other hand, these mixed micelles still had lower values of haemolytic potential than micelles built of C, D or CD. The mixed micelles that included bile acids: 12-oxoL, 7-oxoL, UD or HD did not significantly differ from the micelles of 7,12-dioxolithocholic acid, observing the values of their haemolytic potential. Copyright © 2011 Elsevier B.V. All rights reserved.
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Sinha, L; Liston, R; Testa, H J; Moriarty, K J
1998-09-01
Idiopathic bile acid malabsorption is a poorly recognized cause of chronic diarrhoea. The SeHCAT (75Selenium HomotauroCholic Acid Test) can accurately diagnose this condition. To identify patients with idiopathic bile acid malabsorption, to describe their clinical features, both qualitatively and quantitatively, and to assess the response to cholestyramine. Idiopathic bile acid malabsorption was considered in all patients complaining of chronic diarrhoea. They were included in the study if their SeHCATs were positive (< 15% retention) and secondary causes of bile acid malabsorption were excluded. The response to therapy with cholestyramine was assessed. Nine patients were diagnosed with idiopathic bile acid malabsorption (median SeHCAT retention 8%, range 3-12.6). Their median daily faecal weight was 285 g (range 85-676) and median faecal fat output was 17 mmol/24 h (range 8.3-38.8). Six patients had an immediate response to cholestyramine. There was a marked reduction in stool frequency (median stool frequency pre-treatment 5/day vs. 2/day post-treatment, P = 0.03). Five patients had large volume diarrhoea (faecal weight > 200 g/day) and three had steatorrhoea. Idiopathic bile acid malabsorption, once suspected, especially by documenting true 'large volume' watery diarrhoea or steatorrhoea, is easily diagnosed and response to therapy is often very good. There is often a previous history of gastrointestinal infection and this condition should be considered in patients with chronic diarrhoea of undetermined origin, especially before they are labelled as having irritable bowel syndrome.
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Rees, David O; Crick, Peter J; Jenkins, Gareth J; Wang, Yuqin; Griffiths, William J; Brown, Tim H; Al-Sarireh, Bilal
2017-11-01
Bile acids have been implicated in the development of gastrointestinal malignancies. Both the specific nature of individual bile acids and their concentration appear key factors in the carcinogenic potency of bile. Using liquid chromatography mass spectrometry (LC-MS) we performed quantitative profiling of bile extracted directly from the common bile duct in 30 patients (15 patients with pancreatic cancer and 15 patients with benign disease). Separation and detection of bile acids was performed using a 1.7μm particle size reversed-phase C 18 LC column at a flow rate of 200μL/min with negative electrospray ionization MS. A significant difference (p=0.018) was seen in the concentration of unconjugated cholic acid in the malignant group (0.643mmol/L) compared to the benign group (0.022mmol/L), with an overall significant difference (p=0.04) seen in the level of total unconjugated bile acids in the malignant group (1.816mmol/L) compared to the benign group (0.069mmol/L). This finding may offer the possibility of both understanding the biology of cancer development in the pancreas, as well as offering a potential diagnostic avenue to explore. However, a larger study is necessary to confirm the alterations in bile acid profiles reported here and explore factors such as diet and microbial populations on the bile acid profiles of these patient groups. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Megalin and cubilin expression in gallbladder epithelium and regulation by bile acids.
Erranz, Benjamín; Miquel, Juan Francisco; Argraves, W Scott; Barth, Jeremy L; Pimentel, Fernando; Marzolo, María-Paz
2004-12-01
Cholesterol crystal formation in the gallbladder is a key step in gallstone pathogenesis. Gallbladder epithelial cells might prevent luminal gallstone formation through a poorly understood cholesterol absorption process. Genetic studies in mice have highlighted potential gallstone susceptibility alleles, Lith genes, which include the gene for megalin. Megalin, in conjunction with the large peripheral membrane protein cubilin, mediates the endocytosis of numerous ligands, including HDL/apolipoprotein A-I (apoA-I). Although the bile contains apoA-I and several cholesterol-binding megalin ligands, the expression of megalin and cubilin in the gallbladder has not been investigated. Here, we show that both proteins are expressed by human and mouse gallbladder epithelia. In vitro studies using a megalin-expressing cell line showed that lithocholic acid strongly inhibits and cholic and chenodeoxycholic acids increase megalin expression. The effects of bile acids (BAs) were also demonstrated in vivo, analyzing gallbladder levels of megalin and cubilin from mice fed with different BAs. The BA effects could be mediated by the farnesoid X receptor, expressed in the gallbladder. Megalin protein was also strongly increased after feeding a lithogenic diet. These results indicate a physiological role for megalin and cubilin in the gallbladder and provide support for a role for megalin in gallstone pathogenesis.
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Geenes, Victoria; Lövgren-Sandblom, Anita; Benthin, Lisbet; Lawrance, Dominic; Chambers, Jenny; Gurung, Vinita; Thornton, Jim; Chappell, Lucy; Khan, Erum; Dixon, Peter; Marschall, Hanns-Ulrich; Williamson, Catherine
2014-01-01
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder associated with an increased risk of adverse fetal outcomes. It is characterised by raised maternal serum bile acids, which are believed to cause the adverse outcomes. ICP is commonly treated with ursodeoxycholic acid (UDCA). This study aimed to determine the fetal and maternal bile acid profiles in normal and ICP pregnancies, and to examine the effect of UDCA treatment. Matched maternal and umbilical cord serum samples were collected from untreated ICP (n = 18), UDCA-treated ICP (n = 46) and uncomplicated pregnancy (n = 15) cases at the time of delivery. Nineteen individual bile acids were measured using HPLC-MS/MS. Maternal and fetal serum bile acids are significantly raised in ICP compared with normal pregnancy (p = <0.0001 and <0.05, respectively), predominantly due to increased levels of conjugated cholic and chenodeoxycholic acid. There are no differences between the umbilical cord artery and cord vein levels of the major bile acid species. The feto-maternal gradient of bile acids is reversed in ICP. Treatment with UDCA significantly reduces serum bile acids in the maternal compartment (p = <0.0001), thereby reducing the feto-maternal transplacental gradient. UDCA-treatment does not cause a clinically important increase in lithocholic acid (LCA) concentrations. ICP is associated with significant quantitative and qualitative changes in the maternal and fetal bile acid pools. Treatment with UDCA reduces the level of bile acids in both compartments and reverses the qualitative changes. We have not found evidence to support the suggestion that UDCA treatment increases fetal LCA concentrations to deleterious levels. PMID:24421907
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Geenes, Victoria; Lövgren-Sandblom, Anita; Benthin, Lisbet; Lawrance, Dominic; Chambers, Jenny; Gurung, Vinita; Thornton, Jim; Chappell, Lucy; Khan, Erum; Dixon, Peter; Marschall, Hanns-Ulrich; Williamson, Catherine
2014-01-01
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder associated with an increased risk of adverse fetal outcomes. It is characterised by raised maternal serum bile acids, which are believed to cause the adverse outcomes. ICP is commonly treated with ursodeoxycholic acid (UDCA). This study aimed to determine the fetal and maternal bile acid profiles in normal and ICP pregnancies, and to examine the effect of UDCA treatment. Matched maternal and umbilical cord serum samples were collected from untreated ICP (n = 18), UDCA-treated ICP (n = 46) and uncomplicated pregnancy (n = 15) cases at the time of delivery. Nineteen individual bile acids were measured using HPLC-MS/MS. Maternal and fetal serum bile acids are significantly raised in ICP compared with normal pregnancy (p = <0.0001 and <0.05, respectively), predominantly due to increased levels of conjugated cholic and chenodeoxycholic acid. There are no differences between the umbilical cord artery and cord vein levels of the major bile acid species. The feto-maternal gradient of bile acids is reversed in ICP. Treatment with UDCA significantly reduces serum bile acids in the maternal compartment (p = <0.0001), thereby reducing the feto-maternal transplacental gradient. UDCA-treatment does not cause a clinically important increase in lithocholic acid (LCA) concentrations. ICP is associated with significant quantitative and qualitative changes in the maternal and fetal bile acid pools. Treatment with UDCA reduces the level of bile acids in both compartments and reverses the qualitative changes. We have not found evidence to support the suggestion that UDCA treatment increases fetal LCA concentrations to deleterious levels.
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Changes in the faecal bile acid profile in dogs fed dry food vs high content of beef: a pilot study.
Herstad, Kristin Marie Valand; Rønning, Helene Thorsen; Bakke, Anne Marie; Moe, Lars; Skancke, Ellen
2018-05-11
Dogs are fed various diets, which also include components of animal origin. In humans, a high-fat/low-fibre diet is associated with higher faecal levels of bile acids, which can influence intestinal health. It is unknown how an animal-based diet high in fat and low in fibre influences the faecal bile acid levels and intestinal health in dogs. This study investigated the effects of high intake of minced beef on the faecal bile acid profile in healthy, adult, client-owned dogs (n = 8) in a 7-week trial. Dogs were initially adapted to the same commercial dry food. Thereafter, incremental substitution of the dry food by boiled minced beef over 3 weeks resulted in a diet in which 75% of each dog's total energy requirement was provided as minced beef during week 5. Dogs were subsequently reintroduced to the dry food for the last 2 weeks of the study. The total taurine and glycine-conjugated bile acids, the primary bile acids chenodeoxycholic acid and cholic acid, and the secondary bile acids lithocholic acid, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) were analysed, using liquid chromatography-tandem mass spectrometry. The faecal quantities of DCA were significantly higher in dogs fed the high minced beef diet. These levels reversed when dogs were reintroduced to the dry food diet. The faecal levels of UDCA and taurine-conjugated bile acids had also increased in response to the beef diet, but this was only significant when compared to the last dry food period. These results suggest that an animal-based diet with high-fat/low-fibre content can influence the faecal bile acids levels. The consequences of this for canine colonic health will require further investigation.
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Shi, Yan; Xiong, Jing; Sun, Dongmei; Liu, Wei; Wei, Feng; Ma, Shuangcheng; Lin, Ruichao
2015-08-01
An accurate and sensitive high-performance liquid chromatography method coupled with ultralviolet detection and precolumn derivatization was developed for the simultaneous quantification of the major bile acids in Artificial Calculus bovis, including cholic acid, hyodeoxycholic acid, chenodeoxycholic acid, and deoxycholic acid. The extraction, derivatization, chromatographic separation, and detection parameters were fully optimized. The samples were extracted with methanol by ultrasonic extraction. Then, 2-bromine-4'-nitroacetophenone and 18-crown ether-6 were used for derivatization. The chromatographic separation was performed on an Agilent SB-C18 column (250 × 4.6 mm id, 5 μm) at a column temperature of 30°C and liquid flow rate of 1.0 mL/min using water and methanol as the mobile phase with a gradient elution. The detection wavelength was 263 nm. The method was extensively validated by evaluating the linearity (r(2) ≥ 0.9980), recovery (94.24-98.91%), limits of detection (0.25-0.31 ng) and limits of quantification (0.83-1.02 ng). Seventeen samples were analyzed using the developed and validated method. Then, the amounts of bile acids were analyzed by hierarchical agglomerative clustering analysis and principal component analysis. The results of the chemometric analysis showed that the contents of these compounds reflect the intrinsic quality of artificial Calculus bovis, and two compounds (hyodeoxycholic acid and chenodeoxycholic acid) were the most important markers for quality evaluating. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Colombo, Carla; Crosignani, Andrea; Alicandro, Gianfranco; Zhang, Wujuan; Biffi, Arianna; Motta, Valentina; Corti, Fabiola; Setchell, Kenneth D R
2016-10-01
To evaluate the fasting and postprandial serum bile acid composition in patients with cystic fibrosis-associated liver disease (CFLD) after chronic administration of ursodeoxycholic acid (UDCA) (20 mg/kg/day). The aim was to specifically focus on the extent of biotransformation of UDCA to its hepatotoxic metabolite, lithocholic acid, because of recent concerns regarding the safety of long-term, high-dose UDCA treatment for CFLD. Twenty patients with CFLD (median age 16 years, range: 2.4-35.0) prescribed UDCA therapy for at least 2 years were studied. Total and individual serum bile acids were measured by stable-isotope dilution mass spectrometry, in fasting and 2-hour postprandial samples taken during chronic UDCA (20 mg/kg/day) administration. During chronic UDCA administration (median duration 8 years, IQR: 6-16), UDCA became the predominant serum bile acid in all patients (median, IQR: 3.17, 1.25-5.56 μmol/L) and chenodeoxycholic acid concentrations were greater than cholic acid (1.86, 1.00-4.70 μmol/L vs 0.40, 0.24-2.71 μmol/L). The secondary bile acids, deoxycholate and lithocholate, were present in very low concentrations in fasted serum (<0.05 μmol/L). After UDCA administration, 2-hour postprandial concentrations of both UDCA and chenodeoxycholic acid significantly increased (P < .01), but no significant changes in serum lithocholic acid concentrations were observed. These data do not support recent suggestions that enhanced biotransformation of UDCA to the hepatotoxic secondary bile acid lithocholic occurs when patients with CFLD are treated with relatively high doses of UDCA. Copyright © 2016 Elsevier Inc. All rights reserved.
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Sinakos, Emmanouil; Marschall, Hanns-Ulrich; Kowdley, Kris V.; Befeler, Alex; Keach, Jill; Lindor, Keith
2010-01-01
High-dose (28-30mg/kg/day) ursodeoxycholic acid (UDCA) treatment improves serum liver tests in patients with primary sclerosing cholangitis (PSC) but does not improve survival and is associated with increased rates of serious adverse events. The mechanism for the latter undesired effect remains unclear. High-dose UDCA could result in the production of hepatotoxic bile acids, such as lithocholic acid (LCA), due to limited small bowel absorption of UDCA and conversion of UDCA by bacteria in the colon. We determined the serum bile acid composition in 56 patients with PSC previously enrolled in a randomized, double-blind controlled trial of high dose UDCA versus placebo. Samples for analysis were obtained at baseline and at the end of treatment. The mean changes in UDCA (16.86 vs 0.05 μmol/L) and total bile acid (17.21 vs −0.55 μmol/L) levels were significantly higher in the UDCA group (n=29) compared to placebo (n=27) when pretreatment levels were compared (p<0.0001). LCA was also markedly increased (0.22 vs 0.01 μmol/L) in the UDCA group compared to placebo (p=0.001). No significant changes were detected for cholic acid (CA), deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). Patients (n=9) in the UDCA group who reached clinical endpoints of disease progression (development of cirrhosis, varices, liver transplantation or death) tend to have greater increase in their post-treatment total bile acid levels (34.99 vs 9.21 μmol/L) (p<0.08) compared to those who did not. Conclusion High-dose UDCA treatment in PSC patients results in marked UDCA enrichment and significant expansion of the total serum bile acid pool including lithocholic acid. PMID:20564380
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Zhang, Yong; Kang, Chao; Wang, Xiao-Lan; Zhou, Min; Chen, Meng-Ting; Zhu, Xiao-Hui; Liu, Kai; Wang, Bin; Zhang, Qian-Yong; Zhu, Jun-Dong; Mi, Man-Tian
2018-03-01
In recent decades, the association among diet, gut microbiota, and the risk of colorectal cancer (CRC) has been established. Gut microbiota and associated metabolites, such as bile acids and butyrate, are now known to play a key role in CRC development. The aim of this study is to identify that the progression to CRC is influenced by cholic acid, sodium butyrate, a high-fat diet, or different dose of dihydromyricetin (DMY) interacted with gut microbiota. An AOM/DSS (azoxymethan/dextran sodium sulfate) model is established to study the gut microbiota compsition before and after tumor formation during colitis-induced tumorigenesis. All above dietary factors profoundly influence the composition of gut microbiota and host colonic tumorigenesis. In addition, mice with DMY-modified initial microbiota display different degrees of chemically induced tumorigenesis. Mechanism analysis reveals that gut microbiota-associated chloride channels participated in colon tumorigenesis. Gut microbiota changes occur in the hyperproliferative stage before tumor formation. Gut microbiota and host chloride channels, both of which are regulated by dietary factors, are associated with CRC development. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Gu, Shenghua; Cao, Bei; Sun, Runbin; Tang, Yueqing; Paletta, Janice L.; Wu, Xiao-Lei; Liu, Linsheng; Zha, Weibin; Zhao, Chunyan; Li, Yan; Radlon, Jason M.; Hylemon, Phillip B.; Zhou, Huiping; Aa, Jiye; Wang, Guangji
2014-01-01
Clinic and animal studies demonstrated that oral-administrated berberine had distinct lipid-lowering effect. However, pharmacokinetic studies showed berberine was poorly absorbed into the body so that the levels of berberine in the blood and target tissues were far below the effective concentrations revealed. To probe the underlying mechanism, the effect of berberine on biological system was studied on a high-fat-diet-induced hamster hyperlipidemia model. Our results showed that intragastric-administered berberine was poorly absorbed into circulation and most berberine accumulated in gut content. Although the bioavailability for intragastric-administered berberine was much lower than that of intraperitoneal-administered berberine, it had stronger lipid-lowing effect, indicating gastrointestinal is a potential target for hypolipidemic effect of berberine. Metabolomic study on both serum and gut content showed that oral-administrated berberine significantly regulated molecules involved in lipid metabolism, and increased the generation of bile acids in the hyperlipidemic model. DNA analysis revealed that the oral-administered berberine modulated the gut microbiota, and BBR showed a significant inhibition on the 7α-dehydroxylation conversion of cholic acid to deoxycholic acid, indicating a decreased elimination of bile acids in the gut. However, in model hamsters, elevated bile acids failed to down-regulate the expression and function of CYP7A1 in a negative feed-back way. It was suggested that the hypocholesterolemic effect for oral-administrated berberine is involved in its effect on modulating the turnover of bile acids and farnesoid X receptor signal pathway. PMID:25411028
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Zhang, Linlin; Su, Huizong; Li, Yue; Fan, Yujuan; Wang, Qian; Jiang, Jian; Hu, Yiyang; Chen, Gaofeng; Tan, Bo; Qiu, Furong
2018-03-01
The aim of this study was to determine the effect of ursodeoxycholic acid (UDCA) on the alpha-naphthylisothiocyanate (ANIT)-induced acute and recovery stage of cholestasis model mice. In the acute stage of model mice, pretreatment with UDCA (25, 50, and 100 mg·kg -1 , ig) for 12 days prior to ANIT administration (50 mg·kg -1 , ig) resulted in the dramatic increase in serum biochemistry, with aggrevation of bile infarcts and hepatocyte necrosis. The elevation of beta-muricholic acid (β-MCA), cholic acid (CA), and taurocholic acid (TCA) in serum and liver, and reduction of these bile acids (BAs) in bile was observed. In contrast, in the recovery stage of model mice, treatment with UDCA (25, 50, and 100 mg·kg -1 , ig) for 7 days after ANIT administration (50 mg·kg -1 , ig) resulted in the significant decrease in levels of serum alanine aminotransferase (ALT) and total bile acid (TBA). Liver injury was attenuated, and the levels of TBA, CA, TCA, and β-MCA in the liver were significantly decreased. Additionally, UDCA can upregulate expression of BSEP, but it cannot upregulate expression of AE2. UDCA, which induced BSEP to increase bile acid-dependent bile flow, aggravated cholestasis and liver injury when the bile duct was obstructed in the acute stage of injury in model mice. In contrast, UDCA alleviated cholestasis and liver injury induced by ANIT when the obstruction was improved in the recovery stage. Copyright © 2018. Published by Elsevier Inc.
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NASA Astrophysics Data System (ADS)
Salunke, Deepak B.; Hazra, Braja G.; Gonnade, Rajesh G.; Pore, Vandana S.; Bhadbhade, Mohan M.
2008-12-01
Methyl 3α,7α-diacetoxy-12-oxo-5β-cholan-24-oate 2, methyl 11α-bromo-3α,7α-diacetoxy-12-oxo-5β-cholan-24-oate 3, methyl 11β-bromo-3α,7α-diacetoxy-12-oxo-5β-cholan-24-oate 4 and methyl 11,11-dibromo-3α,7α-diacetoxy-12-oxo-5β-cholan-24-oate 5 were synthesized. The crystal structures of these molecules were resolved to study the effect of bulky bromine atom in the steroid skeleton of cholic acid with different stereo-chemical orientations at C-11 on the two-dimensional arrangement of molecules and solid-state properties. All the molecules associate only via weak intermolecular interactions in their crystal structures, notable one being the Halogen Bonded assembly (C-Br…O) in 5.
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Kong, Weijun; Jin, Cheng; Xiao, Xiaohe; Zhao, Yanling; Liu, Wei; Li, Zulun; Zhang, Ping
2010-06-01
A fast ultra-performance liquid chromatography-evaporative light scattering detection (UPLC-ELSD) method was established for simultaneous quantification of seven components in natural Calculus bovis (C. bovis) and its substitutes or spurious breeds. On a Waters Acquity UPLC BEH C(18) column, seven analytes were efficiently separated using 0.2% aqueous formic acid-acetonitrile as the mobile phase in a gradient program. The evaporator tube temperature of ELSD was set at 100 degrees C with the nebulizing gas flow-rate of 1.9 L/min. The results showed that this established UPLC-ELSD method was validated to be sensitive, precise and accurate with the LODs of seven analytes at 2-11 ng, and the overall intra-day and inter-day variations less than 3.0%. The recovery of the method was in the range of 97.8-101.6%, with RSD less than 3.0%. Further results of PCA on the contents of seven investigated analytes suggested that compounds of cholic acid, deoxycholic acid and chenodeoxycholic acid or cholesterol should be added as chemical markers to UPLC analysis of C. bovis samples for quality control and to discriminate natural C. bovis sample and its substitutes or some spurious breeds, then normalize the use of natural C. bovis and ensure its clinical efficacy.
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Sardella, Roccaldo; Gioiello, Antimo; Ianni, Federica; Venturoni, Francesco; Natalini, Benedetto
2012-10-15
The employment of the flow N-acyl amidation of natural bile acids (BAs) required the in-line connection with suitable analytical tools enabling the determination of reaction yields as well as of the purity grade of the synthesized glyco- and tauro-conjugated derivatives. In this framework, a unique HPLC method was successfully established and validated for ursodeoxycholic (UDCA), chenodeoxycholic (CDCA), deoxycholic (DCA) and cholic (CA) acids, as well as the corresponding glyco- and tauro-conjugated forms. Because of the shared absence of relevant chromophoric moieties in the sample structure, an evaporative light scattering detector (ELSD) was profitably utilized for the analysis of such steroidal species. For each of the investigated compounds, all the runs were contemporarily carried out on the acidic free and the two relative conjugated variants. The different ELSD response of the free and the corresponding conjugated BAs, imposed to build-up separate calibration curves. In all the cases, very good precision (RSD% values ranging from 1.04 to 6.40% in the long-period) and accuracy (Recovery% values ranging from 96.03 to 111.14% in the long-period) values along with appreciably low LOD and LOQ values (the former being within the range 1-27 ng mL(-1) and the latter within the range 2-44 ng mL(-1)) turned out. Copyright © 2012 Elsevier B.V. All rights reserved.
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Sun, Boqiao; Kantzow, Christina; Bresch, Sven; Castiglione, Kathrin; Weuster-Botz, Dirk
2013-01-01
Ursodeoxycholic acid (UDCA) is a bile acid of industrial interest as it is used as an agent for the treatment of primary sclerosing cholangitis and the medicamentous, non-surgical dissolution of gallstones. Currently, it is prepared industrially from cholic acid following a seven-step chemical procedure with an overall yield of <30%. In this study, we investigated the key enzymatic steps in the chemo-enzymatic preparation of UDCA-the two-step reduction of dehydrocholic acid (DHCA) to 12-keto-ursodeoxycholic acid using a mutant of 7β-hydroxysteroid dehydrogenase (7β-HSDH) from Collinsella aerofaciens and 3α-hydroxysteroid dehydrogenase (3α-HSDH) from Comamonas testosteroni. Three different one-pot reaction approaches were investigated using whole-cell biocatalysts in simple batch processes. We applied one-biocatalyst systems, where 3α-HSDH, 7β-HSDH, and either a mutant of formate dehydrogenase (FDH) from Mycobacterium vaccae N10 or a glucose dehydrogenase (GDH) from Bacillus subtilis were expressed in a Escherichia coli BL21(DE3) based host strain. We also investigated two-biocatalyst systems, where 3α-HSDH and 7β-HSDH were expressed separately together with FDH enzymes for cofactor regeneration in two distinct E. coli hosts that were simultaneously applied in the one-pot reaction. The best result was achieved by the one-biocatalyst system with GDH for cofactor regeneration, which was able to completely convert 100 mM DHCA to >99.5 mM 12-keto-UDCA within 4.5 h in a simple batch process on a liter scale. Copyright © 2012 Wiley Periodicals, Inc.
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Duran, María Isabel; González, Cesar; Acosta, Alison; Olea, Andrés F; Díaz, Katy; Espinoza, Luis
2017-03-08
Brassinosteroids (BRs) are plant hormones that promote growth in different plant organs and tissues. The structural requirements that these compounds should possess to exhibit this biological activity have been studied. In this work, a series of known BR analogs 5 - 15 , were synthesized starting from hyodeoxycholic acid 4 , and maintaining the alkyl side chain as cholic acid or its methyl ester. The growth-promoting effects of brassinolide ( 1 ) and synthesized analogs were evaluated by using the rice lamina inclination assay at concentrations ranging from 1 × 10 -8 -1 × 10 -6 M. Our results indicate that in this concentration range the induced bending angle of rice seedlings increases with increasing concentration of BRs. Analysis of the activities, determined at the lowest tested concentration, in terms of BR structures shows that the 2α,3α-dihydroxy-7-oxa-6-ketone moiety existing in brassinolide is required for the plant growing activity of these compounds, as it has been proposed by some structure-activity relationship studies. The effect of compound 8 on cell elongation was assessed by microscopy analysis, and the results indicate that the growth-promoting effect of analog 8 is mainly due to cell elongation of the adaxial sides, instead of an increase on cell number.
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Effect of pelvic irradiation on the absorption of bile acids
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stryker, J.A.; Demers, L.M.
1979-07-01
The pathophysiology of radiation-induced diarrhea was evaluated in 17 patients undergoing pelvic irradiation for gynecological malignancies. The glycine conjugates of cholic acid (GC) and chenodeoxycholic acid (GCDC) were measured in serum by radioimmunoassay. Fasting and 2 hour post prandial (pp) determinations were performed prior to and in the fifth week of radiotherapy. The pre-treatment fasting and 2 hour pp GC levels were 0.20 +- 0.29 (mean +- SD) and 0.48 +- 0.47 ..mu..M. In the fifth week the fasting and 2 hour pp GC levels were 0.16 +- 0.23 and 0.25 +- 0.27 ..mu..M. The first week fasting and 2more » hour pp GCDC levels were 0.32 +- 0.47 and 0.80 +- 0.83 ..mu..M: in the fifth week they were 0.10 +- 0.06 and 0.33 +- 0.27 ..mu..M. The differences between the first and the fifth week post prandial increases in serum GC and GCDC levels were significant (P<0.02). The reduced post prandial increases in serum GC and GCDC in the fifth week of radiotherapy occurred at a time when the patients' daily stool frequencies were significantly increased (P<0.01). The data suggest that a cholerrheic enteropathy is the major determinant in the pathophysiology of radiation-induced diarrhea.« less
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Effects of Low-Dose Non-Caloric Sweetener Consumption on Gut Microbiota in Mice
Uebanso, Takashi; Ohnishi, Ai; Kitayama, Reiko; Yoshimoto, Ayumi; Nakahashi, Mutsumi; Shimohata, Takaaki; Mawatari, Kazuaki; Takahashi, Akira
2017-01-01
Non-caloric artificial sweeteners (NASs) provide sweet tastes to food without adding calories or glucose. NASs can be used as alternative sweeteners for controlling blood glucose levels and weight gain. Although the consumption of NASs has increased over the past decade in Japan and other countries, whether these sweeteners affect the composition of the gut microbiome is unclear. In the present study, we examined the effects of sucralose or acesulfame-K ingestion (at most the maximum acceptable daily intake (ADI) levels, 15 mg/kg body weight) on the gut microbiome in mice. Consumption of sucralose, but not acesulfame-K, for 8 weeks reduced the relative amount of Clostridium cluster XIVa in feces. Meanwhile, sucralose and acesulfame-K did not increase food intake, body weight gain or liver weight, or fat in the epididymis or cecum. Only sucralose intake increased the concentration of hepatic cholesterol and cholic acid. Moreover, the relative concentration of butyrate and the ratio of secondary/primary bile acids in luminal metabolites increased with sucralose consumption in a dose-dependent manner. These results suggest that daily intake of maximum ADI levels of sucralose, but not acesulfame-K, affected the relative amount of the Clostridium cluster XIVa in fecal microbiome and cholesterol bile acid metabolism in mice. PMID:28587159
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Effects of Low-Dose Non-Caloric Sweetener Consumption on Gut Microbiota in Mice.
Uebanso, Takashi; Ohnishi, Ai; Kitayama, Reiko; Yoshimoto, Ayumi; Nakahashi, Mutsumi; Shimohata, Takaaki; Mawatari, Kazuaki; Takahashi, Akira
2017-06-01
Abstract : Non-caloric artificial sweeteners (NASs) provide sweet tastes to food without adding calories or glucose. NASs can be used as alternative sweeteners for controlling blood glucose levels and weight gain. Although the consumption of NASs has increased over the past decade in Japan and other countries, whether these sweeteners affect the composition of the gut microbiome is unclear. In the present study, we examined the effects of sucralose or acesulfame-K ingestion (at most the maximum acceptable daily intake (ADI) levels, 15 mg/kg body weight) on the gut microbiome in mice. Consumption of sucralose, but not acesulfame-K, for 8 weeks reduced the relative amount of Clostridium cluster XIVa in feces. Meanwhile, sucralose and acesulfame-K did not increase food intake, body weight gain or liver weight, or fat in the epididymis or cecum. Only sucralose intake increased the concentration of hepatic cholesterol and cholic acid. Moreover, the relative concentration of butyrate and the ratio of secondary/primary bile acids in luminal metabolites increased with sucralose consumption in a dose-dependent manner. These results suggest that daily intake of maximum ADI levels of sucralose, but not acesulfame-K, affected the relative amount of the Clostridium cluster XIVa in fecal microbiome and cholesterol bile acid metabolism in mice.
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Duran, María Isabel; González, Cesar; Acosta, Alison; Olea, Andrés F.; Díaz, Katy; Espinoza, Luis
2017-01-01
Brassinosteroids (BRs) are plant hormones that promote growth in different plant organs and tissues. The structural requirements that these compounds should possess to exhibit this biological activity have been studied. In this work, a series of known BR analogs 5–15, were synthesized starting from hyodeoxycholic acid 4, and maintaining the alkyl side chain as cholic acid or its methyl ester. The growth-promoting effects of brassinolide (1) and synthesized analogs were evaluated by using the rice lamina inclination assay at concentrations ranging from 1 × 10−8–1 × 10−6 M. Our results indicate that in this concentration range the induced bending angle of rice seedlings increases with increasing concentration of BRs. Analysis of the activities, determined at the lowest tested concentration, in terms of BR structures shows that the 2α,3α-dihydroxy-7-oxa-6-ketone moiety existing in brassinolide is required for the plant growing activity of these compounds, as it has been proposed by some structure-activity relationship studies. The effect of compound 8 on cell elongation was assessed by microscopy analysis, and the results indicate that the growth-promoting effect of analog 8 is mainly due to cell elongation of the adaxial sides, instead of an increase on cell number. PMID:28282853
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Asai, Saori; Kusada, Mio; Watanabe, Suzuyo; Kawashima, Takuji; Nakamura, Tadashi; Shimada, Masaya; Goto, Tsuyoshi; Nagaoka, Satoshi
2014-01-01
Royal jelly (RJ) intake lowers serum cholesterol levels in animals and humans, but the active component in RJ that lowers serum cholesterol level and its molecular mechanism are unclear. In this study, we set out to identify the bile acid-binding protein contained in RJ, because dietary bile acid-binding proteins including soybean protein and its peptide are effective in ameliorating hypercholesterolemia. Using a cholic acid-conjugated column, we separated some bile acid-binding proteins from RJ and identified the major RJ protein 1 (MRJP1), MRJP2, and MRJP3 as novel bile acid-binding proteins from RJ, based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Purified MRJP1, which is the most abundant protein of the bile acid-binding proteins in RJ, exhibited taurocholate-binding activity in vitro. The micellar solubility of cholesterol was significantly decreased in the presence of MRJP1 compared with casein in vitro. Liver bile acids levels were significantly increased, and cholesterol 7α-hydroxylase (CYP7A1) mRNA and protein tended to increase by MRJP1 feeding compared with the control. CYP7A1 mRNA and protein levels were significantly increased by MRJP1 tryptic hydrolysate treatment compared with that of casein tryptic hydrolysate in hepatocytes. MRJP1 hypocholesterolemic effect has been investigated in rats. The cholesterol-lowering action induced by MRJP1 occurs because MRJP1 interacts with bile acids induces a significant increase in fecal bile acids excretion and a tendency to increase in fecal cholesterol excretion and also enhances the hepatic cholesterol catabolism. We have identified, for the first time, a novel hypocholesterolemic protein, MRJP1, in RJ. Interestingly, MRJP1 exhibits greater hypocholesterolemic activity than the medicine β-sitosterol in rats. PMID:25144734
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Bile acid malabsorption in chronic diarrhea: Pathophysiology and treatment
Barkun, Alan; Love, Jonathan; Gould, Michael; Pluta, Henryk; Steinhart, A Hillary
2013-01-01
BACKGROUND: Bile acid malabsorption (BAM) is a common but frequently under-recognized cause of chronic diarrhea, with an estimated prevalence of 4% to 5%. METHODS: The published literature for the period 1965 to 2012 was examined for articles regarding the pathophysiology and treatment of BAM to provide an overview of the management of BAM in gastroenterology practice. RESULTS: BAM is classified as type 1 (secondary to ileal dysfunction), type 2 (idiopathic) or type 3 (secondary to gastrointestinal disorders not associated with ileal dysfunction). The estimated prevalence of BAM is >90% in patients with resected Crohn disease (CD) and 11% to 52% of unresected CD patients (type 1); 33% in diarrhea-predominant irritable bowel syndrome (type 2); and is a frequent finding postcholecystectomy or postvagotomy (type 3). Investigations include BAM fecal bile acid assay, 23-seleno-25-homo-tauro-cholic acid (SeHCAT) testing and high-performance liquid chromatography of serum 7-α-OH-4-cholesten-3-one (C4), to determine the level of bile acid synthesis. A less time-consuming and expensive alternative in practice is an empirical trial of the bile acid sequestering agent cholestyramine. An estimated 70% to 96% of chronic diarrhea patients with BAM respond to short-course cholestyramine. Adverse effects include constipation, nausea, borborygmi, flatulence, bloating and abdominal pain. Other bile acid sequestering agents, such as colestipol and colesevelam, are currently being investigated for the treatment of BAM-associated diarrhea. CONCLUSIONS: BAM is a common cause of chronic diarrhea presenting in gastroenterology practice. In accordance with current guidelines, an empirical trial of a bile acid sequestering agent is warranted as part of the clinical workup to rule out BAM. PMID:24199211
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Prevalence of, and predictors of, bile acid malabsorption in outpatients with chronic diarrhea.
Gracie, D J; Kane, J S; Mumtaz, S; Scarsbrook, A F; Chowdhury, F U; Ford, A C
2012-11-01
Many physicians do not consider the diagnosis of bile acid malabsorption in patients with chronic diarrhea, or do not have access to testing. We examined yield of 23-seleno-25-homo-tauro-cholic acid (SeHCAT) scanning in chronic diarrhea patients, and attempted to identify predictors of a positive test. Consecutive patients with chronic diarrhea undergoing SeHCAT scan over a 7-year period were identified retrospectively. Bile acid malabsorption was defined as present at a retention of <15%. Medical records were reviewed to obtain information regarding proposed risk factors. Gastrointestinal symptoms were recorded, and patients were classified as having diarrhea-predominant irritable bowel syndrome (IBS-D) if they reported abdominal pain or discomfort. Independent risk factors were assessed using multivariate logistic regression, and odds ratios (ORs) with 99% confidence intervals (CIs) were calculated. Of 373 patients, 190 (50.9%) had bile acid malabsorption. Previous cholecystectomy (OR 2.51; 99% CI 1.10-5.77), terminal ileal resection or right hemicolectomy for Crohn's disease (OR 12.4; 99% CI 2.42-63.8), and terminal ileal resection or right hemicolectomy for other reasons (OR 7.94; 99% CI 1.02-61.6) were associated with its presence. Seventy-seven patients had IBS-D, and 21 (27.3%) tested positive. There were 168 patients with no risk factors for a positive SeHCAT scan, other than chronic diarrhea, and 63 (37.5%) had bile acid malabsorption. Bile acid malabsorption was present in 50% of patients undergoing SeHCAT scanning. Almost 40% of those without risk factors had evidence of bile acid malabsorption, and in those meeting criteria for IBS-D prevalence was almost 30%. © 2012 Blackwell Publishing Ltd.
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Sun, Xiaowei; Xu, Wei; Zeng, Yan; Hou, Yurong; Guo, Lin; Zhao, Xiujuan; Sun, Changhao
2014-02-01
The purpose of this study was to investigate the toxic effect of long-term and low-level exposure to phorate using a metabonomics approach based on ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Male Wistar rats were given phorate daily in drinking water at low doses of 0.05, 0.15 or 0.45 mg kg⁻¹ body weight (BW) for 24 weeks consecutively. Rats in the control group were given an equivalent volume of drinking water. Compared with the control group, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), urea nitrogen (BUN) and creatinine (CR) were increased in the middle- and high-dose groups whereas albumin (ALB) and cholinesterase (CHE) were decreased. Urine metabonomics profiles were analyzed by UPLC-MS. Compared with the control group, 12 metabolites were significantly changed in phorate-treated groups. In the negative mode, metabolite intensities of uric acid, suberic acid and citric acid were significantly decreased in the middle- and high-dose groups, whereas indoxyl sulfic acid (indican) and cholic acid were increased. In the positive mode, uric acid, creatinine, kynurenic acid and xanthurenic acid were significantly decreased in the middle- and high-dose groups, but 7-methylguanine (N⁷G) was increased. In both negative and positive modes, diethylthiophosphate (DETP) was significantly increased, which was considered as a biomarker of exposure to phorate. In conclusion, long-term and low-level exposure to phorate can cause disturbances in energy-related metabolism, liver and kidney function, the antioxidant system, and DNA damage. Moreover, more information can be provided on the evaluation of toxicity of phorate using metabonomics combined with clinical chemistry. Copyright © 2012 John Wiley & Sons, Ltd.
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Chemoprevention of esophageal adenocarcinoma in a rat model by ursodeoxycholic acid.
Ojima, Eisuke; Fujimura, Takashi; Oyama, Katsunobu; Tsukada, Tomoya; Kinoshita, Jun; Miyashita, Tomoharu; Tajima, Hidehiro; Fushida, Sachio; Harada, Shin-ichi; Mukaisho, Ken-ichi; Hattori, Takanori; Ohta, Tetsuo
2015-08-01
Reflux of bile acid into the esophagus induces esophagitis, inflammation-stimulated hyperplasia, metaplasia such as Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC). Caudal-type homeobox 2 (Cdx2) via nuclear factor (NF)-κB induced by bile acid is an important factor in the development of BE and EAC. In colorectal cancer, experimental data suggest a chemopreventive effect of ursodeoxycholic acid (UDCA). We hypothesized that UDCA may protect against the esophageal inflammation-metaplasia-carcinoma sequence by decreasing the overall proportion of the toxic bile acids. Wistar male rats that underwent a duodenoesophageal reflux procedure were divided into two groups. One group was given commercial chow (control group), and the other was given experimental chow containing UDCA (UDCA group). The animals were killed at 40 weeks after surgery, and their bile and esophagus were examined. In the UDCA group, the esophagitis was milder and the incidence of BE was significantly lower (p < 0.05) than in the control group, and EAC was not observed (p < 0.05). In analysis of the compartment of bile acid, UDCA was markedly increased in the UDCA group compared with the control group (32.7 ± 11.4 vs. 0.82 ± 0.33 mmol/L, p < 0.05) and cholic acid was decreased (32.7 ± 4.05 vs. 60.9 ± 8.26 mmol/L, p < 0.05). Expression intensity of Cdx2 and NF-κB was greater in the control group than in the UDCA group (p < 0.05). UDCA may be a chemopreventive agent against EAC by varying the bile acid composition.
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Yeo, Siok-Koon; Liong, Min-Tze
2012-11-01
The objective of this study was to evaluate the effects of ultraviolet (UV) radiation (UVB; 90 J/m²) on growth, bioconversion of isoflavones and probiotic properties of parent and subsequent passages of L. casei FTDC 2113. UV radiation significantly enhanced (P < 0.05) the growth of parent cells in mannitol-soymilk fermented at 37°C for 24 h. This had led to an enhanced intracellular and extracellular β-glucosidase activity with a subsequent increase in bioconversion of isoflavones in mannitol-soymilk (P < 0.05). UV radiation also promoted (P < 0.05) the tolerance of parent cells towards acidic condition (pH 2 and 3) and intestinal bile salts (oxgall, taurocholic and cholic acid). In addition, parent treated cells also exhibited better (P < 0.05) adhesion ability to mucin and antimicrobial activity compared to that of the control. All these positive effects of UV radiation were only prevalent in the parent cells without inheritance by first, second and third passage of cells. Although temporary, our results suggested that UV radiation could enhance the bioactive and probiotic potentials of L. casei FTDC 2113, and thus could be applied for the production of probiotic products with enhanced bioactivity.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Schuster, J.J.; Stryker, J.A.; Demers, L.M.
The pathophysiology of chronic radiation-induced diarrhea was evaluated in 28 patients who had undergone pelvic irradiation for gynecologic neoplasms 2 to 7 years previously. Twenty-seven patients undergoing radiotherapy with techniques that did not require abdominal or pelvic irradiation served as controls. The glycine conjugates of cholic acid (GC) were measured in serum by radioimmunoassay. Fasting and 2 hr. pp GC levels for the pelvic irradiated patients were 11.0 +/- 11.1 (mean +/- SD) and 24.8 +/- 17.3 micrograms/dl. Fasting and 2 hr. pp GC levels for controls were 12.6 +/- 7.4 and 28.0 +/- 14.7. There were no significant differencesmore » in the post-prandial increases in serum GC between pelvic irradiated patients and controls (p = .23, Type II error probability = .13). There was also no significant difference in the 2 hr. pp and fasting GC ratio (p = .39). There was significant difference between the stool frequency (p less than .01) and the prevalence of diarrhea (p less than .02) between pelvic irradiated patients and controls. The data suggest that bile acid malabsorption due to ileal dysfunction is not an inevitable late complication of pelvic irradiation and is not the major determinant in the pathophysiology of chronic radiation-induced diarrhea.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Jazrawi, R.P.; Ferraris, R.; Bridges, C.
The apparent fractional turnover rate of the gamma-labeled bile acid analogue 75-selenohomocholic acid-taurine (75-SeHCAT) was assessed from decline in radioactivity over the gallbladder area on 4 successive days using a gamma-camera, and was compared in the same subjects with the fractional turnover rate of the corresponding natural bile acid, cholic acid-taurine, labeled with 14C ((14C)CAT) using the classical Lindstedt technique. Very similar results were obtained in 5 healthy individuals (coefficient of variation 4.8%, medians 0.35 and 0.34, respectively). By contrast, the fractional deconjugation rate assessed from zonal scanning of glycine- and taurine-conjugated bile acids on thin-layer chromatography was much lessmore » for 75-SeHCAT than for (14C)CAT (0.02 and 0.13, respectively; p less than 0.05). The fractional rate for deconjugation plus dehydroxylation was also determined by zonal scanning, and gave lower values for 75-SeHCAT than for (14C)CAT (0.02 and 0.12, respectively; p less than 0.05). There was a striking similarity between the fractional rate for deconjugation alone and that for deconjugation plus dehydroxylation for both bile acids in individual samples (r = 0.999, p less than 0.001), suggesting that these two processes might occur simultaneously and probably involve the same bacteria. We conclude that our scintiscanning technique provides an accurate, noninvasive method of measuring fractional turnover rate of a bile acid in humans, and that the finding that 75SeHCAT remains conjugated with taurine during enterohepatic recycling means that absorption should be specific for the ileal active transport site, thus rendering it an ideal substance for assessing ileal function.« less
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EXOCRINE FUNCTION OF THE LIVER IN RATS WITH EXPOSURE TO CОRVITIN.
Vovkun, T V; Yanchuk, P I; Shtanova, L Y; Vesеlskyу, S P; Shalamaу, A S
In acute experiments on rats with cannulated bile duct we studied the effect of Corvitin, water-soluble analogue of quercetin, on secretion of bile. Intraportal administration of the test compound at doses of 2,5; 5 and 10 mg/kg resulted in a significant increase in the volume of secreted bile by 20,9, 31,2 and 20,4%, respectively, as compared with the control. Using the method of thin layer chromatography it was established the mild stimulating effect of Corvitin on the processes of bile acids conjugation with taurine and glycine, especially when administered at a dose of 5 mg/kg. This flavonoid did not affect the concentration of glycocholic acid, however increased the content of glycochenodeoxycholic and glycodeoxycholic acids in the mixture between 15 to 35,1%. Regarding free bile acids, the concentration of cholic acid, chenodeoxycholic and deoxycholic acids in the mixture was increased significantly relative to control only after Corvitin application at dose 10 mg/ kg. In the first case – from 17,9 to 29,8%, in the second – from 25 to 65,4%. At the dose of 5 mg/kg, Corvitin significantly increased the ratio of bile cholates conjugation (maximum by 23,2%), whereas 10 mg/kg of the drug decreased this index by 27,0%. After administration of Corvitin, the hydroxylation ratio in all experimental groups differed little from the control: at the dose of 5 and 10 mg/kg this parameter decreased by 14%. Thus, Corvitin modulates exocrine function of the liver, causing an increase in bile secretion and concentration of different cholates, dose-dependently increasing or decreasing the effectiveness of multienzyme systems providing processes of bile acids conjugation in rats.
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Metformin impacts cecal bile acid profiles in mice.
Sillner, Nina; Walker, Alesia; Koch, Wendelin; Witting, Michael; Schmitt-Kopplin, Philippe
2018-04-15
Bile acids (BAs) are major components of bile synthesized from cholesterol and take part in the digestion of dietary lipids, as well as having signaling functions. They undergo extensive microbial metabolism inside the gastrointestinal tract. Here, we present a method of ultra-high pressure liquid chromatography coupled to ion trap mass spectrometry for quantification of 45 BAs in mouse cecum. The system was validated in regard to sensitivity with limits of detection and quantification (0.6-24.9 nM), interday accuracy (102.4%), interday precision (15.2%), recovery rate (74.7%), matrix effect (98.2%) and carry-over effect (<1.1%). Afterwards, we applied our method to investigate the effect of metformin on BA profiles. Diabetic mice were treated with metformin for 1 day or 14 days. One day of treatment resulted in a significant increase of total BA concentration (2.7-fold increase; db/db metformin 5.32 μmol/g, db/db control mice 1.95 μmol/g), most notable in levels of 7-oxodeoxycholic, 3-dehydrocholic and cholic acid. We observed only minor impact on BA metabolism after 14 days of metformin treatment, compared to the single treatment. Furthermore, healthy wild type mice had elevated concentrations of allocholic and ω-muricholic acid compared to diabetic mice. Our method proved the applicability of profiling BAs in cecum to investigate intestinal BA metabolism in diabetes and pharmacological applications. Copyright © 2018 Elsevier B.V. All rights reserved.
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Park, Hye Min; Shon, Jong Cheol; Lee, Mee Youn; Liu, Kwang-Hyeon; Kim, Jeong Kee; Lee, Sang Jun; Lee, Choong Hwan
2014-01-01
Although many studies have been performed on the effects of ultraviolet (UV) radiation on the skin, only a limited number of reports have investigated these effects on non-skin tissue. This study aimed to describe the metabolite changes in the liver of hairless mice following chronic exposure to UVB radiation. We did not observe significant macroscopic changes or alterations in hepatic cholesterol and triglyceride levels in the liver of UVB-irradiated mice, compared with those for normal mice. In this study, we detected hepatic metabolite changes by UVB exposure and identified several amino acids, fatty acids, nucleosides, carbohydrates, phospholipids, lysophospholipids, and taurine-conjugated cholic acids as candidate biomarkers in response to UVB radiation in the mouse liver by using various mass spectrometry (MS)-based metabolite profiling including ultra-performance liquid chromatography-quadrupole time-of-flight (TOF)-MS, gas chromatography-TOF-MS and nanomate LTQ-MS. Glutamine exhibited the most dramatic change with a 5-fold increase in quantity. The results from altering several types of metabolites suggest that chronic UVB irradiation may impact significantly on major hepatic metabolism processes, despite the fact that the liver is not directly exposed to UVB radiation. MS-based metabolomic approach for determining regulatory hepatic metabolites following UV irradiation will provide a better understanding of the relationship between internal organs and UV light.
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Xiong, Zhili; Yang, Jie; Huang, Yue; Zhang, Kuo; Bo, Yunhai; Lu, Xiumei; Su, Guangyue; Ma, Jie; Yang, Jingyu; Zhao, Longshan; Wu, Chunfu
2016-09-01
Xiao-Chai-Hu-Tang (XCHT) has been proven to be effective for the clinical treatment of depression. However, the mechanisms of definite antidepressant-like effects and detailed metabolic biomarkers were still unclear in this prior study. Here, we have investigated the metabolic profiles and potential biomarkers in a chronic unpredictable mild stress model after treatment with XCHT. Metabonomics based on ultra-high performance liquid chromatography coupled with mass spectrometry was used to profile the metabolic fingerprints of serum obtained from a rat model with chronic unpredictable mild stress with and without XCHT treatment. The model rats showed a significant decrease in sucrose preference and food consumption, and these depression-like symptoms were significantly improved by XCHT. Through principal component analysis (PCA), nine potential biomarkers of tryptophan, uric acid, phenylalanine, cholic acid and lysophosphatidylcholine (C18:0 LPC, C16:0 LPC, C16:1 LPC, C18:1 LPC, C20:4 LPC) were characterized as potential biomarkers involved the pathogenesis of depression. The therapeutic effect of XCHT on depression may involve in amino acid metabolism, lipid metabolism, oxidative stress and inflammation response. The present investigation highlights that metabonomics is a valuable tool for studying the essence of depression as well as evaluating the efficacy of the corresponding drug treatment. Copyright © 2016 Elsevier B.V. All rights reserved.
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Hou, Yuanyuan; Nie, Yan; Cheng, Binfeng; Tao, Jin; Ma, Xiaoyao; Jiang, Min; Gao, Jie; Bai, Gang
2016-01-01
Gram-negative pathogen–induced nosocomial infections and resistance are a most serious menace to global public health. Qingfei Xiaoyan Wan (QF), a traditional Chinese medicine (TCM) formula, has been used clinically in China for the treatment of upper respiratory tract infections, acute or chronic bronchitis and pulmonary infection. In this study, the effects of QF on Pseudomonas aeruginosa–induced acute pneumonia in mice were evaluated. The mechanisms by which four typical anti-inflammatory ingredients from QF, arctigenin (ATG), cholic acid (CLA), chlorogenic acid (CGA) and sinapic acid (SPA), regulate anti-inflammatory signaling pathways and related targets were investigated using molecular biology and molecular docking techniques. The results showed that pretreatment with QF significantly inhibits the release of cytokines (TNF-α and IL-6) and chemokines (IL-8 and RANTES), reduces leukocytes recruitment into inflamed tissues and ameliorates pulmonary edema and necrosis. In addition, ATG was identified as the primary anti-inflammatory agent with action on the PI3K/AKT and Ras/MAPK pathways. CLA and CGA enhanced the actions of ATG and exhibited synergistic NF-κB inactivation effects possibly via the Ras/MAPK signaling pathway. Moreover, CLA is speculated to target FGFR and MEK firstly. Overall, QF regulated the PI3K/AKT and Ras/MAPK pathways to inhibit pathogenic bacterial infections effectively. PMID:27175332
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Jurate, Kondrackiene; Rimantas, Zalinkevicius; Jolanta, Sumskiene; Vladas, Gintautas; Limas, Kupcinskas
2017-01-01
Intrahepatic cholestasis of pregnancy (ICP) is linked with increased risk of fetal complications. An accurate diagnostic test is needed to diagnose this disorder on time. We aimed to assess sensitivity and specificity of laboratory tests used for diagnosis of intrahepatic cholestasis of pregnancy and determine more reliable cut-off values of transaminases. Sixty one symptomatic patients with ICP and 29 healthy pregnant women were included in the retrospective analysis. ICP patients had higher total bile acids (TBA) levels than healthy women (32 vs. 6; P < 0.0001) due to increase in cholic acid (CA) and chenodeoxycholic acid (CDCA). CA/CDCA ratio was significantly higher in ICP patients compared to healthy pregnant women (1.13 vs. 0.68; P < 0.00002). TBA, CA, CDCA and CA/CDCA ratio demonstrate the following sensitivity (94%, 96%, 89%, 71.9%) and specificity (63%, 63%, 59%, 79.3%, respectively) for ICP diagnosis. Lowering cut-off values for ALT (31 U/L) and AST (30 U/L) resulted only in minimal increase of sensitivity to 92.2% vs. 90.1% for ALT and to 92.2%, vs. 90.6% for AST. The present study did not reveal any single specific and sensitive marker for reliable diagnosis of ICP. Establishment of lower cut-off values for transaminases activity might only minimally increase the accuracy of diagnosing ICP.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Lake, April D.; Novak, Petr; Shipkova, Petia
2013-04-15
Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BAmore » profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids are observed in NASH. ► Hepatic bile acid synthesis shifts toward the alternative pathway in NASH.« less
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Posa, Mihalj; Pilipović, Ana; Lalić, Mladena
2010-11-01
Many of bile acids' (BA) physiological properties, as receptor binding, activation of ionic channels, binding to blood proteins, etc. are due to their hydrophobicity. On the other hand, hydrophobicity determines BAs' physico-chemical characteristics as micelle forming and adsorption (surface activity). However, BA hydrophobicity is not determined solely by their structure. Medium composition, especially the concentration of electrolytes has influence on BA hydrophobicity. Thus, the objective of this work was to examine the effect of NaCl on hydrophobicity of selected bile acids. This influence is specified with the retention factor k (reversed phase high pressure liquid chromatography (RPHPLC)) and critical micellar concentration (CMC) determined by non-invasive NMR method. The value of lnk elevates with the increase in mobile phase NaCl concentration i.e. Deltalnk/Deltac(NaCl) depends on the number of water molecules not stabilised by hydrogen bonds in bile acid hydration sheath. For bile acids that contain hydroxyl groups (except those with beta equatorial hydroxyl groups) the value of |DeltalnCMC/Deltac(NaCl)| rises with the increase in the number of non-stabilized water molecules in their hydration sheath. Even though oxo derivatives of cholic acid have similar chromatographic parameters they behave differently when it comes to CMC. In fact with the introduction of oxo groups the value of its |DeltalnCMC/Deltac(NaCl)| elevates but it results in a decrease in the number of non-stabilized water molecules i.e. hydrophobicity falls. Different behaviour of oxo derivatives implicate that, besides "hydrophobic interactions" in their micelles, there are also hydrogen bonds i.e. fiord effect exists. Copyright (c) 2010 Elsevier B.V. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Fu, Zidong Donna; Klaassen, Curtis D., E-mail: cklaasse@kumc.edu
Previous studies showed glucose and insulin signaling can regulate bile acid (BA) metabolism during fasting or feeding. However, limited knowledge is available on the effect of calorie restriction (CR), a well-known anti-aging intervention, on BA homeostasis. To address this, the present study utilized a “dose–response” model of CR, where male C57BL/6 mice were fed 0, 15, 30, or 40% CR diets for one month, followed by BA profiling in various compartments of the enterohepatic circulation by UPLC-MS/MS technique. This study showed that 40% CR increased the BA pool size (162%) as well as total BAs in serum, gallbladder, and smallmore » intestinal contents. In addition, CR “dose-dependently” increased the concentrations of tauro-cholic acid (TCA) and many secondary BAs (produced by intestinal bacteria) in serum, such as tauro-deoxycholic acid (TDCA), DCA, lithocholic acid, ω-muricholic acid (ωMCA), and hyodeoxycholic acid. Notably, 40% CR increased TDCA by over 1000% (serum, liver, and gallbladder). Interestingly, 40% CR increased the proportion of 12α-hydroxylated BAs (CA and DCA), which correlated with improved glucose tolerance and lipid parameters. The CR-induced increase in BAs correlated with increased expression of BA-synthetic (Cyp7a1) and conjugating enzymes (BAL), and the ileal BA-binding protein (Ibabp). These results suggest that CR increases BAs in male mice possibly through orchestrated increases in BA synthesis and conjugation in liver as well as intracellular transport in ileum. - Highlights: • Dose response effects of short-term CR on BA homeostasis in male mice. • CR increased the BA pool size and many individual BAs. • CR altered BA composition (increased proportion of 12α-hydroxylated BAs). • Increased mRNAs of BA enzymes in liver (Cyp7a1 and BAL) and ileal BA binding protein.« less
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Wunsch, Ewa; Trottier, Jocelyn; Milkiewicz, Malgorzata; Raszeja-Wyszomirska, Joanna; Hirschfield, Gideon M; Barbier, Olivier; Milkiewicz, Piotr
2014-09-01
Ursodeoxycholic acid (UDCA) is no longer recommended for management of adult patients with primary sclerosing cholangitis (PSC). We undertook a prospective evaluation of UDCA withdrawal in a group of consecutive patients with PSC. Twenty six patients, all treated with UDCA (dose range: 10-15 mg/kg/day) were included. Paired blood samples for liver biochemistry, bile acids, and fibroblast growth factor 19 (FGF19) were collected before UDCA withdrawal and 3 months later. Liquid chromatography/tandem mass spectrometry was used for quantification of 29 plasma bile acid metabolites. Pruritus and health-related quality of life (HRQoL) were assessed with a 10-point numeric rating scale, the Medical Outcomes Study Short Form-36 (SF-36), and PBC-40 questionnaires. UDCA withdrawal resulted in a significant deterioration in liver biochemistry (increase of alkaline phosphatase of 75.6%; P<0.0001; gamma-glutamyl transpeptidase of 117.9%, P<0.0001; bilirubin of 50.0%, P<0.001; alanine aminotransferase of 63.9%, P<0.005; and aspartate aminotransferase of 45.0%, P<0.005) and increase of Mayo Risk Score for PSC (change from baseline of +0.5 point; P<0.003). Bile acid analysis revealed a significant decrease in lithocholic acid and its derivatives after UDCA withdrawal, but no effect on concentrations of primary bile acids aside from an increased accumulation of their taurine conjugates. After UDCA removal cholestatic parameters, taurine species of cholic acid and chenodeoxycholic acid correlated with serum FGF19 levels. No significant effect on HRQoL after UDCA withdrawal was observed; however, 42% of patients reported a deterioration in their pruritus. At 3 months, discontinuation of UDCA in patients with PSC causes significant deterioration in liver biochemistry and influences concentrations of bile acid metabolites. A proportion of patients report increased pruritus, but other short-term markers of quality of life are unaffected. © 2014 by the American Association for the Study of Liver Diseases.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Egner, Timothy K.; Naik, Pranjali; Nelson, Nicholas C.
Engineering nanoparticle (NP) functions at the molecular level requires a detailed understanding of the dynamic processes occurring at the NP surface. Herein we show that a combination of dark-state exchange saturation transfer (DEST) and relaxation dispersion (RD) NMR experiments on gel-stabilized NP samples enables the accurate determination of the kinetics and thermodynamics of adsorption. We used the former approach to describe the interaction of cholic acid (CA) and phenol (PhOH) with ceria NPs with a diameter of approximately 200 nm. Whereas CA formed weak interactions with the NPs, PhOH was tightly bound to the NP surface. Interestingly, we found thatmore » the adsorption of PhOH proceeds via an intermediate, weakly bound state in which the small molecule has residual degrees of rotational diffusion. Here we believe the use of aqueous gels for stabilizing NP samples will increase the applicability of solution NMR methods to the characterization of nanomaterials.« less
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Egner, Timothy K.; Naik, Pranjali; Nelson, Nicholas C.; ...
2017-06-22
Engineering nanoparticle (NP) functions at the molecular level requires a detailed understanding of the dynamic processes occurring at the NP surface. Herein we show that a combination of dark-state exchange saturation transfer (DEST) and relaxation dispersion (RD) NMR experiments on gel-stabilized NP samples enables the accurate determination of the kinetics and thermodynamics of adsorption. We used the former approach to describe the interaction of cholic acid (CA) and phenol (PhOH) with ceria NPs with a diameter of approximately 200 nm. Whereas CA formed weak interactions with the NPs, PhOH was tightly bound to the NP surface. Interestingly, we found thatmore » the adsorption of PhOH proceeds via an intermediate, weakly bound state in which the small molecule has residual degrees of rotational diffusion. Here we believe the use of aqueous gels for stabilizing NP samples will increase the applicability of solution NMR methods to the characterization of nanomaterials.« less
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Si, Xiao-yun; Jia, Ru-han; Huang, Cong-xin; Ding, Guo-hua; Liu, Hong-yan
2003-09-01
To evaluate the effect of Valeriana officinalis var latifolia(VOL) on expression of transforming growth factor beta 1 (TGF-beta 1) in hypercholesterolemic rats and study its possible mechanisms. Dietary-induced hypercholesterolemia was induced in male Wistar rats by given 4% cholesterol and 1% cholic acid diet for 16 weeks. Changes of serum lipid, urinary albumin, renal function and Mesangial matrix index were assessed. Moreover, immunohistochemical stain for TGF-beta 1 and type IV collagen were performed. VOL could reduce the serum levels of total cholesterol, low density lipoprotein, urinary albumin and serum creatinine. Light microscopy and immunohistochemical stain revealed that in the same time of lowing serum lipid, Mesangial matrix index was significantly reduced, accompanied by decreased expression of TGF-beta 1 and type IV collagen. VOL has the protective effect on lipid-induced nephropathy, and the inhibition of TGF-beta 1 expression might be the mechanism of VOL on renal protection.
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König, Alexander; Döring, Barbara; Mohr, Christina; Geipel, Andreas; Geyer, Joachim; Glebe, Dieter
2014-10-01
The human liver bile acid transporter Na(+)/taurocholate cotransporting polypeptide (NTCP) has recently been identified as liver-specific receptor for infection of hepatitis B virus (HBV), which attaches via the myristoylated preS1 (myr-preS1) peptide domain of its large surface protein to NTCP. Since binding of the myr-preS1 peptide to NTCP is an initiating step of HBV infection, we investigated if this process interferes with the physiological bile acid transport function of NTCP. HBV infection, myr-preS1 peptide binding, and bile acid transport assays were performed with primary Tupaia belangeri (PTH) and human (PHH) hepatocytes as well as NTCP-transfected human hepatoma HepG2 cells allowing regulated NTCP expression, in the presence of various bile acids, ezetimibe, and myr-preS1 peptides. The myr-preS1 peptide of HBV inhibited bile acid transport in PTH and PHH as well as in NTCP-expressing HEK293 and HepG2 cells. Inversely, HBV infection of PTH, PHH, and NTCP-transfected HepG2 cells was inhibited in a concentration-dependent manner by taurine and glycine conjugates of cholic acid and ursodeoxycholic acid as well as by ezetimibe. In NTCP-HepG2 cells and PTH, NTCP expression, NTCP transport function, myr-preS1 peptide binding, and HBV infection followed comparable kinetics. Myr-preS1 virus binding to NTCP, necessary for productive HBV infection, interferes with the physiological bile acid transport function of NTCP. Therefore, HBV infection via NTCP may be lockable by NTCP substrates and NTCP-inhibiting drugs. This opens a completely new way for an efficient management of HBV infection by the use of NTCP-directed drugs. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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In Vitro Modeling of Bile Acid Processing by the Human Fecal Microbiota.
Martin, Glynn; Kolida, Sofia; Marchesi, Julian R; Want, Elizabeth; Sidaway, James E; Swann, Jonathan R
2018-01-01
Bile acids, the products of concerted host and gut bacterial metabolism, have important signaling functions within the mammalian metabolic system and a key role in digestion. Given the complexity of the mega-variate bacterial community residing in the gastrointestinal tract, studying associations between individual bacterial genera and bile acid processing remains a challenge. Here, we present a novel in vitro approach to determine the bacterial genera associated with the metabolism of different primary bile acids and their potential to contribute to inter-individual variation in this processing. Anaerobic, pH-controlled batch cultures were inoculated with human fecal microbiota and treated with individual conjugated primary bile acids (500 μg/ml) to serve as the sole substrate for 24 h. Samples were collected throughout the experiment (0, 5, 10, and 24 h) and the bacterial composition was determined by 16S rRNA gene sequencing and the bile acid signatures were characterized using a targeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) approach. Data fusion techniques were used to identify statistical bacterial-metabolic linkages. An increase in gut bacteria associated bile acids was observed over 24 h with variation in the rate of bile acid metabolism across the volunteers ( n = 7). Correlation analysis identified a significant association between the Gemmiger genus and the deconjugation of glycine conjugated bile acids while the deconjugation of taurocholic acid was associated with bacteria from the Eubacterium and Ruminococcus genera. A positive correlation between Dorea and deoxycholic acid production suggest a potential role for this genus in cholic acid dehydroxylation. A slower deconjugation of taurocholic acid was observed in individuals with a greater abundance of Parasutterella and Akkermansia . This work demonstrates the utility of integrating compositional (metataxonomics) and functional (metabonomics) systems biology approaches, coupled to in vitro model systems, to study the biochemical capabilities of bacteria within complex ecosystems. Characterizing the dynamic interactions between the gut microbiota and the bile acid pool enables a greater understanding of how variation in the gut microbiota influences host bile acid signatures, their associated functions and their implications for health.
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Mander, Poonam; Yoo, Hah-Young; Kim, Seung Wook; Choi, Yun Hee; Cho, Seung Sik; Yoo, Jin Cheol
2014-02-01
The aim of this present study was to produce a microbial enzyme that can potentially be utilized for the enzymatic transesterification of waste cooking oil. To that end, an extracellular lipase was isolated and purified from the culture broth of Streptomyces sp. CS273. The molecular mass of purified lipase was estimated to be 36.55 kDa by SDS PAGE. The optimum lipolytic activity was obtained at alkaline pH 8.0 to 8.5 and temperature 40 °C, while the enzyme was stable in the pH range 7.0 ∼ 9.0 and at temperature ≤40 °C. The lipase showed highest hydrolytic activity towards p-nitrophenyl myristate (C14). The lipase activity was enhanced by several salts and detergents including NaCl, MnSo₄, and deoxy cholic acid, while phenylmethylsulfonyl fluoride at concentration 10 mM inhibited the activity. The lipase showed tolerance towards different organic solvents including ethanol and methanol which are commonly used in transesterification reactions to displace alcohol from triglycerides (ester) contained in renewable resources to yield fatty acid alkyl esters known as biodiesel. Applicability of the lipase in transesterification of waste cooking oil was confirmed by gas chromatography mass spectrometry analysis.
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Henry, Hugues; Bruce, Stephen J.; Aeby, Sébastien; Rosikiewicz, Marta; Sykiotis, Gerasimos P.; Asrih, Mohammed; Jornayvaz, François R.; Denechaud, Pierre Damien; Mohammadi, Moosa; Acierno, James S.; Schoonjans, Kristina; Pitteloud, Nelly
2017-01-01
β-Klotho (encoded by Klb) is the obligate coreceptor mediating FGF21 and FGF15/19 signaling. Klb–/– mice are refractory to beneficial action of pharmacological FGF21 treatment including stimulation of glucose utilization and thermogenesis. Here, we investigated the energy homeostasis in Klb–/– mice on high-fat diet in order to better understand the consequences of abrogating both endogenous FGF15/19 and FGF21 signaling during caloric overload. Surprisingly, Klb–/– mice are resistant to diet-induced obesity (DIO) owing to enhanced energy expenditure and BAT activity. Klb–/– mice exhibited not only an increase but also a shift in bile acid (BA) composition featured by activation of the classical (neutral) BA synthesis pathway at the expense of the alternative (acidic) pathway. High hepatic production of cholic acid (CA) results in a large excess of microbiota-derived deoxycholic acid (DCA). DCA is specifically responsible for activating the TGR5 receptor that stimulates BAT thermogenic activity. In fact, combined gene deletion of Klb and Tgr5 or antibiotic treatment abrogating bacterial conversion of CA into DCA both abolish DIO resistance in Klb–/– mice. These results suggested that DIO resistance in Klb–/– mice is caused by high levels of DCA, signaling through the TGR5 receptor. These data also demonstrated that gut microbiota can regulate host thermogenesis via conversion of primary into secondary BA. Pharmacologic or nutritional approaches to selectively modulate BA composition may be a promising target for treating metabolic disorders. PMID:28422755
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Liaset, Bjørn; Hao, Qin; Jørgensen, Henry; Hallenborg, Philip; Du, Zhen-Yu; Ma, Tao; Marschall, Hanns-Ulrich; Kruhøffer, Mogens; Li, Ruiqiang; Li, Qibin; Yde, Christian Clement; Criales, Gabriel; Bertram, Hanne C.; Mellgren, Gunnar; Øfjord, Erik Snorre; Lock, Erik-Jan; Espe, Marit; Frøyland, Livar; Madsen, Lise; Kristiansen, Karsten
2011-01-01
Bile acids (BAs) are powerful regulators of metabolism, and mice treated orally with cholic acid are protected from diet-induced obesity, hepatic lipid accumulation, and increased plasma triacylglycerol (TAG) and glucose levels. Here, we show that plasma BA concentration in rats was elevated by exchanging the dietary protein source from casein to salmon protein hydrolysate (SPH). Importantly, the SPH-treated rats were resistant to diet-induced obesity. SPH-treated rats had reduced fed state plasma glucose and TAG levels and lower TAG in liver. The elevated plasma BA concentration was associated with induction of genes involved in energy metabolism and uncoupling, Dio2, Pgc-1α, and Ucp1, in interscapular brown adipose tissue. Interestingly, the same transcriptional pattern was found in white adipose tissue depots of both abdominal and subcutaneous origin. Accordingly, rats fed SPH-based diet exhibited increased whole body energy expenditure and heat dissipation. In skeletal muscle, expressions of the peroxisome proliferator-activated receptor β/δ target genes (Cpt-1b, Angptl4, Adrp, and Ucp3) were induced. Pharmacological removal of BAs by inclusion of 0.5 weight % cholestyramine to the high fat SPH diet attenuated the reduction in abdominal obesity, the reduction in liver TAG, and the decrease in nonfasted plasma TAG and glucose levels. Induction of Ucp3 gene expression in muscle by SPH treatment was completely abolished by cholestyramine inclusion. Taken together, our data provide evidence that bile acid metabolism can be modulated by diet and that such modulation may prevent/ameliorate the characteristic features of the metabolic syndrome. PMID:21680746
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Biliary Bile Acids in Primary Biliary Cirrhosis: Effect of Ursodeoxycholic Acid
Combes, Burton; Carithers, Robert L.; Maddrey, Willis C.; Munoz, Santiago; Garcia-Tsao, Guadalupe; Bonner, Gregory F.; Boyer, James L.; Luketic, Velimir A.; Shiffman, Mitchell L.; Peters, Marion G.; White, Heather; Zetterman, Rowen K.; Risser, Richard; Rossi, Stephen S.; Hofmann, Alan F.
2014-01-01
Bile acid composition in fasting duodenal bile was assessed at entry and at 2 years in patients with primary biliary cirrhosis (PBC) enrolled in a randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) (10–12 mg/kg/d) taken as a single bedtime dose. Specimens were analyzed by a high-pressure liquid chromatography method that had been validated against gas chromatography. Percent composition in bile (mean ± SD) for 98 patients at entry for cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA), lithocholic (LCA), and ursodeoxycholic (UDCA) acids, respectively, were 57.4 ± 18.6, 31.5 ± 15.5, 8.0 ± 9.3, 0.3 ± 1.0, and 0.6 ± 0.9. Values for CA were increased, whereas those for CDCA, DCA, LCA, and UDCA were decreased when compared with values in normal persons. Bile acid composition of the major bile acids did not change after 2 years on placebo medication. By contrast, in patients receiving UDCA for 2 years, bile became enriched with UDCA on average to 40.1%, and significant decreases were noted for CA (to 32.2%) and CDCA (to 19.5%). No change in percent composition was observed for DCA and LCA. Percent composition at entry and changes in composition after 2 years on UDCA were similar in patients with varying severity of PBC. In patients whose bile was not enriched in UDCA (entry and placebo-treated specimens), CA, CDCA, DCA, and the small amount of UDCA found in some of these specimens were conjugated to a greater extent with glycine (52%–64%) than with taurine (36%–48%). Treatment with UDCA caused the proportion of all endogenous bile acids conjugated with glycine to increase to 69% to 78%, while the proportion conjugated with taurine (22%–31%) fell (P < .05). Administered UDCA was also conjugated predominantly with glycine (87%). PMID:10347103
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Ghaffarzadegan, Tannaz; Marungruang, Nittaya; Fåk, Frida; Nyman, Margareta
2016-01-01
Bile acids (BAs) act as signaling molecules in various physiological processes, and are related to colonic microbiota composition as well as to different types of dietary fat and fiber. This study investigated whether guar gum and pectin—two fibers with distinct functional characteristics—affect BA profiles, microbiota composition, and gut metabolites in rats. Low- (LM) or high-methoxylated (HM) pectin, and low-, medium-, or high-molecular-weight (MW) guar gum were administered to rats that were fed either low- or high-fat diets. Cecal BAs, short-chain fatty acids (SCFA) and microbiota composition, and plasma lipopolysaccharide-binding protein (LBP) levels were analyzed, by using novel methodologies based on gas chromatography (BAs and SCFAs) and 16S rRNA gene sequencing on the Illumina MiSeq platform. Strong correlations were observed between cecal BA and SCFA levels, microbiota composition, and portal plasma LBP levels in rats on a high-fat diet. Notably, guar gum consumption with medium-MW increased the cecal amounts of cholic-, chenodeoxycholic-, and ursodeoxycholic acids as well as α-, β-, and ω-muricholic acids to a greater extent than other types of guar gum or the fiber-free control diet. In contrast, the amounts of cecal deoxycholic- and hyodeoxycholic acid were reduced with all types of guar gum independent of chain length. Differences in BA composition between pectin groups were less obvious, but cecal levels of α- and ω-muricholic acids were higher in rats fed LM as compared to HM pectin or the control diet. The inflammatory marker LBP was downregulated in rats fed medium-MW guar gum and HM pectin; these two fibers decreased the cecal abundance of Oscillospira and an unclassified genus in Ruminococcaceae, and increased that of an unclassified family in RF32. These results indicate that the molecular properties of guar gum and pectin are important for their ability to modulate cecal BA formation, gut microbiota composition, and high-fat diet induced inflammation. PMID:27315087
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Gilat, T; Somjen, G; Mazur, Y; Leikin-Frenkel, A; Rosenberg, R; Halpern, Z; Konikoff, F.
2001-01-01
BACKGROUND—Cholesterol gall stones are a frequent disease for which at present surgery is the usual therapy. Despite the importance of bile acids it has become evident that phospholipids are the main cholesterol solubilisers in bile. Even phospholipid components, such as fatty acids, have anticrystallising activity. AIM—To synthesise fatty acid bile acid conjugates (FABACs) and study their effects on cholesterol crystallisation in bile in vitro and in vivo. METHODS—FABACs were prepared by conjugation of cholic acid at position 3 with saturated fatty acids of variable chain length using an amide bond. Cholesterol crystallisation and its kinetics (crystal observation time, crystal mass) were studied in model bile, pooled enriched human bile, and fresh human bile using FABACs with saturated fatty acids of varying chain length (C-6 to C-22). Absorption of FABACs into blood and bile was tested in hamsters. Prevention of biliary cholesterol crystallisation in vivo was tested in hamsters and inbred mice. RESULTS—FABACs strongly inhibited cholesterol crystallisation in model as well as native bile. The FABACs with longer acyl chains (C-16 to C-22) were more effective. At a concentration of 5 mM, FABACs almost completely inhibited cholesterol crystallisation in fresh human bile for 21 days. FABACs were absorbed and found in both portal and heart blood of hamsters. Levels in bile were 2-3 times higher than in blood, indicating active secretion. Appreciable levels were found in the systemic circulation 24-48 hours after a single administration. Ingested FABACs completely prevented the formation of cholesterol crystals in the gall bladders of hamsters and mice fed a lithogenic diet. CONCLUSIONS—FABACs are potent inhibitors of cholesterol crystallisation in bile. They are absorbed and secreted into bile and prevent the earliest step of cholesterol gall stone formation in animals. These compounds may be of potential use in cholesterol gall stone disease in humans. Keywords: gall stones; bile; phospholipids; cholesterol crystallisation; fatty acid bile acid conjugates PMID:11115826
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No significant effect of the SLCO1B1 polymorphism on the pharmacokinetics of ursodeoxycholic acid.
Xiang, Xiaoqiang; Vakkilainen, Juha; Backman, Janne T; Neuvonen, Pertti J; Niemi, Mikko
2011-11-01
To investigate possible effects of the SLCO1B1 polymorphism on the pharmacokinetics of ursodeoxycholic acid (UDCA) and its metabolites in healthy volunteers. In a crossover study with two phases, 15 healthy volunteers with the SLCO1B1*1A/*1A genotype, seven with the *1B/*1B genotype, and five with the *15/*15 or *5/*15 genotype ingested placebo or a single 150-mg dose of UDCA. Plasma concentrations of bile acids and their biosynthesis marker were determined up to 24 h post-ingestion by liquid chromatography-tandem mass spectrometry. The SLCO1B1 genotype had no significant effect on the pharmacokinetics of UDCA. The geometric mean ratios (95% confidence interval) of UDCA area under the plasma concentration-time curve from 0 to 12 h (AUC(0-12)) in subjects with the SLCO1B1*1B/*1B genotype and in subjects with the SLCO1B1*15/*15 or *5/*15 genotype to the AUC(0-12) in subjects with the SLCO1B1*1A/*1A genotype were 1.07 (0.85, 1.35; P = 0.459) and 0.93 (0.75, 1.15; P = 0.563), respectively. In addition, following either placebo or UDCA administration, the SLCO1B1 polymorphism showed no association with the AUC(0-24) of the glycine and taurine conjugates of UDCA, with endogenous bile acids, or with the incremental AUC(0-24) of a bile acid synthesis marker. Compared with placebo, UDCA ingestion increased the AUC(0-24) of cholic acid, glycochenodeoxycholic acid, glycocholic acid, and glycodeoxycholic acid by 1.5-, 1.1-, 1.2-, and 1.2- fold (P < 0.05), respectively. Genetic polymorphism in SLCO1B1 does not affect pharmacokinetics of UDCA, suggesting that OATP1B1 is not rate-limiting to the hepatic uptake of therapeutic UDCA. Further studies are required to clarify the mechanisms by which UDCA increases the plasma concentrations of endogenous bile acids.
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Nerandzic, Michelle M.; Donskey, Curtis J.
2017-01-01
Background Clostridium difficile is a leading cause of healthcare-associated infections worldwide. Prevention of C. difficile transmission is challenging because spores are not killed by alcohol-based hand sanitizers or many commonly used disinfectants. One strategy to control spores is to induce germination, thereby rendering the spores more susceptible to benign disinfection measures and ambient stressors. Methods/Results C. difficile spores germinated on skin after a single application of cholic acid-class bile salts and co-germinants; for 4 C. difficile strains, recovery of viable spores from skin was reduced by ~0.3 log10CFU to 2 log10CFU after 2 hours and ~1 log10CFU to > 2.5 log10CFU after 24 hours. The addition of taurocholic acid to 70% and 30% ethanol significantly enhanced reduction of viable spores on skin and on surfaces. Desiccation, and to a lesser extent the presence of oxygen, were identified as the stressors responsible for reductions of germinated spores on skin and surfaces. Additionally, germinated spores became susceptible to killing by pH 1.5 hydrochloric acid, suggesting that germinated spores that remain viable on skin and surfaces might be killed by gastric acid after ingestion. Antibiotic-treated mice did not become colonized after exposure to germinated spores, whereas 100% of mice became colonized after exposure to the same quantity of dormant spores. Conclusions Germination could provide a new approach to reduce C. difficile spores on skin and in the environment and to render surviving spores less capable of causing infection. Our findings suggest that it may be feasible to develop alcohol-based hand sanitizers containing germinants that reduce spores on hands. PMID:29167835
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Potential Functional Byproducts from Guava Purée Processing.
Lim, Si Yi; Tham, Paik Yean; Lim, Hilary Yi Ler; Heng, Wooi Shin; Chang, Ying Ping
2018-05-10
The valorization of guava waste requires compositional and functional studies. We tested three byproducts of guava purée processing, namely refiner, siever, and decanter. We analyzed the chemical composition and quantified the prebiotic activity score and selected carbohydrates; we also determined the water holding (WHC), oil holding (OHC), cation exchange capacities, bile acid binding, and glucose dialysis retardation (GDR) of the solid fraction and the antioxidative and α-amylase inhibitory capacities (AIC) of the ethanolic extract. Refiner contained 7.7% lipid, 7.08% protein and a relatively high phytate content; it had a high prebiotic activity score and possessed the highest binding capacity with deoxycholic acid. Siever contained high levels of low molecular weight carbohydrates and total tannin but relatively low crude fiber and cellulose contents. It had the highest binding with chenodeoxycholic acid (74.8%), and exhibited the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity. Decanter was rich in cellulose and had a high prebiotic activity score. The WHC and OHC values of decanter were within a narrow range and also exhibited the highest binding with cholic acid (86.6%), and the highest values of GDR and AIC. The refiner waste could be included in animal feed but requires further processing to reduce the high phytate levels. All three guava byproducts had the potential to be a source of antioxidant dietary fiber (DF), a finding that warrants further in vivo study. To differing extents, the guava byproducts exhibited useful physicochemical binding properties and so possessed the potential for health-promoting activity. These byproducts could also be upgraded to other marketable products so the manufacturers of processed guava might be able to develop their businesses sustainably by making better use of them. © 2018 Institute of Food Technologists®.
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Wang, Yingfeng; Man, Hongxue; Gao, Jian; Liu, Xinfeng; Ren, Xiaolei; Chen, Jianxin; Zhang, Jiayu; Gao, Kuo; Li, Zhongfeng; Zhao, Baosheng
2016-09-01
Lang-du (LD) has been traditionally used to treat human diseases in China. Plasma metabolic profiling was applied in this study based on LC-MS to elucidate the toxicity in rats induced by injected ethanol extract of LD. LD injection was given by intraperitoneal injection at doses of 0.1, 0.05, 0.025 and 0 g kg(-1) body weight per day to rats. The blood biochemical levels of alanine aminotransferase, direct bilirubin, creatinine, serum β2-microglobulin and low-density lipoprotein increased in LD-injected rats, and the levels of total protein and albumin decreased in these groups. The metabolic profiles of the samples were analyzed by multivariate statistics analysis, including principal component analysis, partial least squares discriminant analysis and orthogonal projection to latent structures discriminate analysis (OPLS-DA). The metabolic characters in rats injected with LD were perturbed in a dose-dependent manner. By OPLS-DA, 18 metabolites were served as the potential toxicity biomarkers. Moreover, LD treatment resulted in an increase in the p-cresol, p-cresol sulfate, lysophosphatidylethanolamine (LPE) (18:0), LPE (16:0), lysophosphatidylcholine (16:0) and 12-HETE concentrations, and a decrease in hippuric acid, cholic acid and N-acetyl-l-phenylalanine. These results suggested that chronic exposure to LD could cause a disturbance in lipids metabolism and amino acids metabolism, etc. Therefore, an analysis of the metabolic profiles can contribute to a better understanding of the adverse effects of LD. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
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Cheema, Amrita K.; Mehta, Khyati Y.; Fatanmi, Oluseyi O.; Wise, Stephen Y.; Wolff, Josh
2017-01-01
The development of radiation countermeasures for acute radiation syndrome (ARS) has been underway for the past six decades, leading to the identification of multiple classes of radiation countermeasures. However, to date, only two growth factors (Neupogen and Neulasta) have been approved by the United States Food and Drug Administration (US FDA) for the mitigation of hematopoietic acute radiation syndrome (H-ARS). No radioprotector for ARS has been approved by the FDA yet. Gamma-tocotrienol (GT3) has been demonstrated to have radioprotective efficacy in murine as well as nonhuman primate (NHP) models. Currently, GT3 is under advanced development as a radioprotector that can be administered prior to radiation exposure. We are studying this agent for its safety profile and efficacy using the NHP model. In this study, we analyzed global metabolomic and lipidomic changes using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS) in serum samples of NHPs administered GT3. Our study, using 12 NHPs, demonstrates that alterations in metabolites manifest only 24 h after GT3 administration. Furthermore, metabolic changes are associated with transient increase in the bioavailability of antioxidants, including lactic acid and cholic acid and anti-inflammatory metabolites 3 deoxyvitamin D3, and docosahexaenoic acid. Taken together, our results show that the administration of GT3 to NHPs causes metabolic shifts that would provide an overall advantage to combat radiation injury. This initial assessment also highlights the utility of metabolomics and lipidomics to determine the underlying physiological mechanisms involved in the radioprotective efficacy of GT3. PMID:29283379
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The influence of bile salts on the distribution of simvastatin in the octanol/buffer system.
Đanić, Maja; Pavlović, Nebojša; Stanimirov, Bojan; Vukmirović, Saša; Nikolić, Katarina; Agbaba, Danica; Mikov, Momir
2016-01-01
Distribution coefficient (D) is useful parameter for evaluating drugs permeability properties across biological membranes, which are of importance for drugs bioavailability. Given that bile acids are intensively studied as drug permeation-modifying and -solubilizing agents, the aim of this study was to estimate the influence of sodium salts of cholic (CA), deoxycholic (DCA) and 12-monoketocholic acids (MKC) on distribution coefficient of simvastatin (SV) (lactone [SVL] and acid form [SVA]) which is a highly lipophilic compound with extremely low water solubility and bioavailability. LogD values of SVA and SVL with or without bile salts were measured by liquid-liquid extraction in n-octanol/buffer systems at pH 5 and 7.4. SV concentrations in aqueous phase were determined by HPLC-DAD. Chem3D Ultra program was applied for computation of physico-chemical properties of analyzed compounds and their complexes. Statistically significant decrease in both SVA and SVL logD was observed for all three studied bile salts at both selected pH. MKC exerted the most pronounced effect in the case of SVA while there were no statistically significant differences between observed bile salts for SVL. The calculated physico-chemical properties of analyzed compounds and their complexes supported experimental results. Our data indicate that the addition of bile salts into the n-octanol/buffer system decreases the values of SV distribution coefficient at both studied pH values. This may be the result of the formation of hydrophilic complexes increasing the solubility of SV that could consequently impact the pharmacokinetic parameters of SV and the final drug response in patients.
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Zhang, Jie; Fan, Yeqin; Gong, Yajun; Chen, Xiaoyong; Wan, Luosheng; Zhou, Chenggao; Zhou, Jiewen; Ma, Shuangcheng; Wei, Feng; Chen, Jiachun; Nie, Jing
2017-11-15
Snake bile is one of the most expensive traditional Chinese medicines (TCMs). However, due to the complicated constitutes of snake bile and the poor ultraviolet absorbance of some trace bile acids (BAs), effective analysis methods for snake bile acids were still unavailable, making it difficult to solve adulteration problems. In present study, ultrahigh-performance liquid chromatography with triple quadrupole linear ion trap mass spectrometry (UHPLC-QqQ-MS/MS) was applied to conduct a quantitative analysis on snake BAs. The mass spectrometer was monitored in the negative ion mode, and multiple-reaction monitoring (MRM) program was used to determine the contents of BAs in snake bile. In all, 61 snake bile from 17 commonly used species of three families (Elapidae, Colubridae and Viperidae), along with five batches of commercial snake bile from four companies, were collected and detected. Nine components, Tauro-3α,12α-dihydroxy-7-oxo-5β-cholenoic acid (T1), Tauro-3α,7α,12α,23R-tetrahydroxy-5β-cholenoic acid (T2), taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), taurodeoxycholic acid (TDCA), cholic acid (CA), Tauro-3α,7α-dihydroxy-12-oxo-5β-cholenoic acid (T3), and Tauro-3α,7α,9α,16α-tetrahydroxy-5β-cholenoic acid (T4) were simultaneously and rapidly determined for the first time. In these BAs, T1 and T2, self-prepared with purity above 90%, were first reported with their quantitative determination, and the latter two (T3 and T4) were tentatively determined by quantitative analysis multi-components by single marker (QAMS) method for roughly estimating the components without reference. The developed method was validated with acceptable linearity (r 2 ≥0.995), precision (RSD＜6.5%) and recovery (RSD＜7.5%). It turned out that the contents of BAs among different species were also significantly different; T1 was one of the principle bile acids in some common snake bile, and also was the characteristic one in Viperidae and Elapidae; T2 was the dominant components in Enhydris chinensis. This quantitative study of BAs in snake bile is a remarkable improvement for clarifying the bile acid compositions and evaluating the quality of snake bile. Copyright © 2017 Elsevier B.V. All rights reserved.
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Ye, Jian-Zhong; Li, Ya-Ting; Wu, Wen-Rui; Shi, Ding; Fang, Dai-Qiong; Yang, Li-Ya; Bian, Xiao-Yuan; Wu, Jing-Jing; Wang, Qing; Jiang, Xian-Wan; Peng, Cong-Gao; Ye, Wan-Chun; Xia, Peng-Cheng; Li, Lan-Juan
2018-06-21
To investigate changes in gut microbiota and metabolism during nonalcoholic steatohepatitis (NASH) development in mice fed a methionine-choline-deficient (MCD) diet. Twenty-four male C57BL/6J mice were equally divided into four groups and fed a methionine-choline-sufficient diet for 2 wk (Control 2w group, n = 6) or 4 wk (Control 4w group, n = 6) or the MCD diet for 2 wk (MCD 2w group, n = 6) or 4 wk (MCD 4w group, n = 6). Liver injury, fibrosis, and intestinal barrier function were evaluated after 2 and 4 wk of feeding. The fecal microbiome and metabolome were studied using 16s rRNA deep sequencing and gas chromatography-mass spectrometry. The mice fed the MCD diet presented with simple hepatic steatosis and slight intestinal barrier deterioration after 2 wk. After 4 wk of feeding with the MCD diet, however, the mice developed prominent NASH with liver fibrosis, and the intestinal barrier was more impaired. Compared with the control diet, the MCD diet induced gradual gut microbiota dysbiosis, as evidenced by a marked decrease in the abundance of Alistipes and the ( Eubacterium ) coprostanoligenes group ( P < 0.001 and P < 0.05, respectively) and a significant increase in Ruminococcaceae UCG 014 abundance ( P < 0.05) after 2 wk. At 4 wk, the MCD diet significantly reduced the promising probiotic Bifidobacterium levels and markedly promoted Bacteroides abundance ( P < 0.05, and P < 0.01, respectively). The fecal metabolomic profile was also substantially altered by the MCD diet: At 2 wk, arachidic acid, hexadecane, palmitic acid, and tetracosane were selected as potential biomarkers that were significantly different in the corresponding control group, and at 4 wk, cholic acid, cholesterol, arachidic acid, tetracosane, and stearic acid were selected. The MCD diet induced persistent alterations in the gut microbiota and metabolome.
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Ye, Jian-Zhong; Li, Ya-Ting; Wu, Wen-Rui; Shi, Ding; Fang, Dai-Qiong; Yang, Li-Ya; Bian, Xiao-Yuan; Wu, Jing-Jing; Wang, Qing; Jiang, Xian-Wan; Peng, Cong-Gao; Ye, Wan-Chun; Xia, Peng-Cheng; Li, Lan-Juan
2018-01-01
AIM To investigate changes in gut microbiota and metabolism during nonalcoholic steatohepatitis (NASH) development in mice fed a methionine-choline-deficient (MCD) diet. METHODS Twenty-four male C57BL/6J mice were equally divided into four groups and fed a methionine-choline-sufficient diet for 2 wk (Control 2w group, n = 6) or 4 wk (Control 4w group, n = 6) or the MCD diet for 2 wk (MCD 2w group, n = 6) or 4 wk (MCD 4w group, n = 6). Liver injury, fibrosis, and intestinal barrier function were evaluated after 2 and 4 wk of feeding. The fecal microbiome and metabolome were studied using 16s rRNA deep sequencing and gas chromatography-mass spectrometry. RESULTS The mice fed the MCD diet presented with simple hepatic steatosis and slight intestinal barrier deterioration after 2 wk. After 4 wk of feeding with the MCD diet, however, the mice developed prominent NASH with liver fibrosis, and the intestinal barrier was more impaired. Compared with the control diet, the MCD diet induced gradual gut microbiota dysbiosis, as evidenced by a marked decrease in the abundance of Alistipes and the (Eubacterium) coprostanoligenes group (P < 0.001 and P < 0.05, respectively) and a significant increase in Ruminococcaceae UCG 014 abundance (P < 0.05) after 2 wk. At 4 wk, the MCD diet significantly reduced the promising probiotic Bifidobacterium levels and markedly promoted Bacteroides abundance (P < 0.05, and P < 0.01, respectively). The fecal metabolomic profile was also substantially altered by the MCD diet: At 2 wk, arachidic acid, hexadecane, palmitic acid, and tetracosane were selected as potential biomarkers that were significantly different in the corresponding control group, and at 4 wk, cholic acid, cholesterol, arachidic acid, tetracosane, and stearic acid were selected. CONCLUSION The MCD diet induced persistent alterations in the gut microbiota and metabolome. PMID:29930468
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Heumen, Bjorn W.H. van, E-mail: b.vanheumen@mdl.umcn.nl; Roelofs, Hennie M.J.; Morsche, Rene H.M. te
Chemoprevention would be a desirable strategy to avoid duodenectomy in patients with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis. We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2 expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells derived from a patient with FAP, were exposed to low dose celecoxib and UDCA alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co-treatment with low dose celecoxib and UDCA resulted in a decreased cellmore » growth (14-17%, p < 0.01). A more pronounced decrease (23-27%, p < 0.01) was observed in LT97 cells. Cell growth of HT-29 cells exposed to 'artificial bile' enriched with UDCA, was decreased (p < 0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with 'artificial bile' enriched with UDCA, cell growth was decreased only in the presence of celecoxib (p < 0.05). No clear evidence was found for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the cellular processes leading to the observed changes in cell growth. In conclusion, co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on colorectal adenoma cells derived from a patient with FAP, and further research on this combination as promising chemopreventive strategy is desired. -- Highlights: Black-Right-Pointing-Pointer Celecoxib and UDCA acid co-treatment decreases cell growth in colon tumor cells. Black-Right-Pointing-Pointer UDCA enriched 'artificial bile' decreases LT-97 cell growth only in presence of celecoxib. Black-Right-Pointing-Pointer PCNA, caspase-3, nor COX-2 seem to be involved in the observed changes in cell growth.« less
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Wang, Wenbo; Zhao, Linlin; He, Zhenyu; Wu, Ning; Li, Qiuxia; Qiu, Xinjian; Zhou, Lu; Wang, Dongsheng
2018-06-12
Ge-Gen-Jiao-Tai-Wan (GGJTW) formula, derived from traditional Chinese herbal medicine, is composed of Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep (Ge-Gen in Chinese), Coptis chinensis Franch (Huang-Lian), and Cinnamomum cassia (L.) J. Presl (Rou-Gui). GGJTW is used for treatment of diabetes in China, reflecting the potent hypoglycemic effect of its ingredients. However, little is known of the hypoglycemic effect of GGJTW and the underlying metabolic mechanism. This study aimed to investigate the hypoglycemic effect of GGJTW in type 2 diabetic rats and the metabolic mechanism of action. Ultra high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UHPLC-QTOF/MS)-based metabolomics approach was used for monitoring hyperglycaemia induced by high-sugar high-fat fodder and streptozotocin (STZ), and the protective effect of GGJTW. Dynamic fasting blood glucose (FBG) levels, body weight, and biochemical parameters, including lipid levels, hepatic-renal function, and hepatic histopathology were used to confirm the hyperglycaemic toxicity and attenuation effects. An orthogonal partial least squared-discriminant analysis (OPLS-DA) approach highlighted significant differences in the metabolome of the healthy control, diabetic, and drug-treated rats. The metabolomics pathway analysis (MetPA) and Kyoto encyclopedia of genes and genomes (KEGG) database were used to investigate the underlying metabolic pathways. Metabolic profiling revealed 37 metabolites as the most potential biomarker metabolites distinguishing GGJTW-treated rats from model rats. Most of the metabolites were primarily associated with bile acid metabolism and lipid metabolism. The most critical pathway was primary bile acid biosynthesis pathway involving the up-regulation of the levels of cholic acid (CA), chenodeoxycholic acid (CDCA), taurocholic acid (TCA), glycocholic acid (GCA), taurochenodesoxycholic acid (TCDCA), and taurine. The significantly-altered metabolite levels indicated the hypoglycemic effect of GGJTW on diabetic rats and the underlying metabolic mechanism. This study will be meaningful for the clinical application of GGJTW and valuable for further exploration of the mechanism. Copyright © 2018 Elsevier B.V. All rights reserved.
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Song, Young Ho; Shin, Eyoung; Wang, Hong; Nolan, Jim; Low, Susan; Parsons, Donald; Zale, Stephen; Ashton, Susan; Ashford, Marianne; Ali, Mir; Thrasher, Daniel; Boylan, Nicholas; Troiano, Greg
2016-05-10
The present studies were aimed at formulating AZD2811-loaded polylactic acid-polyethylene glycol (PLA-PEG) nanoparticles with adjustable release rates without altering the chemical structures of the polymer or active pharmaceutical ingredient (API). This was accomplished through the use of a hydrophobic ion pairing approach. A series of AZD2811-containing nanoparticles with a variety of hydrophobic counterions including oleic acid, 1-hydroxy-2-naphthoic acid, cholic acid, deoxycholic acid, dioctylsulfosuccinic acid, and pamoic acid is described. The hydrophobicity of AZD2811 was increased through formation of ion pairs with these hydrophobic counterions, producing nanoparticles with exceptionally high drug loading-up to five fold higher encapsulation efficiency and drug loading compared to nanoparticles made without hydrophobic ion pairs. Furthermore, the rate at which the drug was released from the nanoparticles could be controlled by employing counterions with various hydrophobicities and structures, resulting in release half-lives ranging from about 2 to 120h using the same polymer, nanoparticle size, and nanoemulsion process. Process recipe variables affecting drug load and release rate were identified, including pH and molarity of quench buffer. Ion pair formation between AZD2811 and pamoic acid as a model counterion was investigated using solubility enhancement as well as nuclear magnetic resonance spectroscopy to demonstrate solution-state interactions. Further evidence for an ion pairing mechanism of controlled release was provided through the measurement of API and counterion release profiles using high-performance liquid chromatography, which had stoichiometric relationships. Finally, Raman spectra of an AZD2811-pamoate salt compared well with those of the formulated nanoparticles, while single components (AZD2811, pamoic acid) alone did not. A library of AZD2811 batches was created for analytical and preclinical characterization. Dramatically improved preclinical efficacy and tolerability data were generated for the pamoic acid lead formulation, which has been selected for evaluation in a Phase 1 clinical trial (ClinicalTrials.gov Identifier NCT 02579226). This work clearly demonstrates the importance of assessing a wide range of drug release rates during formulation screening as a critical step for new drug product development, and how utilizing hydrophobic ion pairing enabled this promising nanoparticle formulation to proceed into clinical development. Copyright © 2016 Elsevier B.V. All rights reserved.
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Feng, Shi-Ting; Li, Jingguo; Luo, Yanji; Yin, Tinghui; Cai, Huasong; Wang, Yong; Dong, Zhi; Shuai, Xintao; Li, Zi-Ping
2014-01-01
The triblock copolymers PEG-P(Asp-DIP)-P(Lys-Ca) (PEALCa) of polyethylene glycol (PEG), poly(N-(N',N'-diisopropylaminoethyl) aspartamide) (P(Asp-DIP)), and poly (lysine-cholic acid) (P(Lys-Ca)) were synthesized as a pH-sensitive drug delivery system. In neutral aqueous environment such as physiological environment, PEALCa can self-assemble into stable vesicles with a size around 50-60 nm, avoid uptake by the reticuloendothelial system (RES), and encase the drug in the core. However, the PEALCa micelles disassemble and release drug rapidly in acidic environment that resembles lysosomal compartments. The anticancer drug Paclitaxel (PTX) and hydrophilic superparamagnetic iron oxide (SPIO) were encapsulated inside the core of the PEALCa micelles and used for potential cancer therapy. Drug release study revealed that PTX in the micelles was released faster at pH 5.0 than at pH 7.4. Cell culture studies showed that the PTX-SPIO-PEALCa micelle was effectively internalized by human colon carcinoma cell line (LoVo cells), and PTX could be embedded inside lysosomal compartments. Moreover, the human colorectal carcinoma (CRC) LoVo cells delivery effect was verified in vivo by magnetic resonance imaging (MRI) and histology analysis. Consequently effective suppression of CRC LoVo cell growth was evaluated. These results indicated that the PTX-SPION-loaded pH-sensitive micelles were a promising MRI-visible drug release system for colorectal cancer therapy.
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Diagnostic Methods for Bile Acid Malabsorption in Clinical Practice
Vijayvargiya, Priya; Camilleri, Michael; Shin, Andrea; Saenger, Amy
2013-01-01
Altered bile acid (BA) concentrations in the colon may cause diarrhea or constipation. BA malabsorption (BAM) accounts for >25% of patients with irritable bowel syndrome (IBS) with diarrhea and chronic diarrhea in Western countries. As BAM is increasingly recognized, proper diagnostic methods are desired in clinical practice to help direct the most effective treatment course for the chronic bowel dysfunction. This review appraises the methodology, advantages and disadvantages of 4 tools that directly measure BAM: 14C-glycocholate breath and stool test, 75Selenium HomotauroCholic Acid Test (SeHCAT), 7 α-hydroxy-4-cholesten-3-one (C4) and fecal BAs. 14C-glycocholate is a laborious test no longer widely utilized. 75SeHCAT is validated, but not available in the United States. Serum C4 is a simple, accurate method that is applicable to a majority of patients, but requires further clinical validation. Fecal measurements to quantify total and individual fecal BAs are technically cumbersome and not widely available. Regrettably, none of these tests are routinely available in the U.S., and a therapeutic trial with a BA binder is used as a surrogate for diagnosis of BAM. Recent data suggest there is an advantage to studying fecal excretion of the individual BAs and their role in BAM; this may constitute a significant advantage of the fecal BA method over the other tests. Fecal BA test could become a routine addition to fecal fat measurement in patients with unexplained diarrhea. In summary, availability determines the choice of test among C4, SeHCAT and fecal BA; more widespread availability of such tests would enhance clinical management of these patients. PMID:23644387
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Mooranian, Armin; Negrulj, Rebecca; Arfuso, Frank; Al-Salami, Hani
2016-11-01
We have shown that the primary bile acid, cholic acid (CA), has anti-diabetic effects in vivo. Probucol (PB) is a lipophilic drug with potential applications in type 2 diabetes (T2D). This study aimed to encapsulate CA with PB and examine the formulation and surface characteristics of the microcapsules. We also tested the microcapsules' biological effects on pancreatic β-cells. Using the polymer, sodium alginate (SA), two formulations were prepared: PB-SA (control), and PB-CA-SA (test). Complete characterizations of the morphology, shape, size, chemical, thermal, and rheological properties, swelling and mechanical strength, cross-sectional imaging (Micro CT), stability, Zeta-potential, drug contents, and PB release profile were carried out, at different temperature and pH values. The microcapsules were applied to a NIT-1 cell culture and the supernatant was analyzed for insulin and TNF-α concentrations. CA incorporation optimized the PB microcapsules, which exhibited pseudoplastic-thixotropic rheological characteristics. The size of the microcapsules remained similar after CA addition, and the microcapsules showed even drug distribution and no chemical alterations of the excipients. Micro-CT imaging, differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy showed consistent microcapsules with uniform shape and morphology. PB-CA-SA microcapsules enhanced NIT-1 cell viability under hyperglycemic states and resulted in improved insulin release as well as reduced cytokine production at the physiological glucose levels. The addition of the primary bile acid, CA, improved the physical properties of the microcapsules and enhanced their pharmacological activity in vitro, suggesting potential applications in diabetes treatment.
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Kim, Kang Ho; Choi, Jong Min; Li, Feng; Arizpe, Armando; Wooton-Kee, Clavia Ruth; Anakk, Sayeepriyadarshini; Jung, Sung Yun; Finegold, Milton J; Moore, David D
2018-06-01
Progressive familial intrahepatic cholestasis (PFIC) is a genetically heterogeneous disorder of bile flow disruption due to abnormal canalicular transport or impaired bile acid (BA) metabolism, causing excess BA accumulation and liver failure. We previously reported an intrahepatic cholestasis mouse model based on loss of function of both farnesoid X receptor (FXR; NR1H4) and a small heterodimer partner (SHP; NR0B2) [double knockout (DKO)], which has strong similarities to human PFIC5. We compared the pathogenesis of DKO livers with that of another intrahepatic cholestasis model, Bsep-/-, which represents human PFIC2. Both models exhibit severe hepatomegaly and hepatic BA accumulation, but DKO showed greater circulating BA and liver injury, and Bsep-/- had milder phenotypes. Molecular profiling of BAs uncovered specific enrichment of cholic acid (CA)-derived BAs in DKO livers but chenodeoxycholate-derived BAs in Bsep-/- livers. Transcriptomic and proteomic analysis revealed specific activation of CA synthesis and alternative basolateral BA transport in DKO but increased chenodeoxycholic acid synthesis and canalicular transport in Bsep-/-. The constitutive androstane receptor (CAR)/pregnane X receptor (PXR)-CYP2B/CYP2C axis is activated in DKO livers but not in other cholestasis models. Loss of this axis in Fxr:Shp:Car:Pxr quadruple knockouts blocked Cyp2b/Cyp2c gene induction, impaired bilirubin conjugation/elimination, and increased liver injury. Differential CYP2B expression in DKO and Bsep-/- was recapitulated in human PFIC5 and PFIC2 livers. In conclusion, loss of FXR/SHP results in distinct molecular pathogenesis and CAR/PXR activation, which promotes Cyp2b/Cyp2c gene transcription and bilirubin clearance. CAR/PXR activation was not observed in Bsep-/- mice or PFIC2 patients. These findings provide a deeper understanding of the heterogeneity of intrahepatic cholestasis.
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Policosanol as a new inhibitor candidate for vascular calcification in diabetic hyperlipidemic rats.
Elseweidy, Mohamed M; Zein, Nabila; Aldhamy, Samih E; Elsawy, Marwa M; Saeid, Saeid A
2016-11-01
This work mainly aimed to investigate the probable changes of aortic calcification by policosanol, omega-3 fatty acids in comparison with atorvastatin and subsequent progression of atherosclerosis in diabetic hyperlipemic rat model. Adult male albino rats of wistar strain (30) were divided into five groups (n = 6/group); one was fed normal diet and was used as a normal group, the other groups received alloxan, atherogenic diet (CCT - rat chow diet supplemented with 4% cholesterol, 1% cholic acid, and 0.5% thiouracil) and categorized as follows: the second group received no treatment and kept as control (diabetic hyperlipidemic control group (DHC)). The other groups received daily oral doses of atorvastatin, policosanol (10 mg/kg body weight) and ω-3 (50 mg/kg body weight), respectively, for eight weeks. Different biomarkers were used for the evaluation that included inflammatory (C reactive protein (CRP), tumor necrosis factor α (TNF-α)), oxidative stress (glutathione (GSH), malondialdehyde (MDA)) bone calcification markers (alkaline phosphatase (ALP), Vitamin D, parathyroid hormone (PTH)), lipogram pattern in addition to histochemical demonstration of calcium in the aorta. Diabetic hyperlipemic group demonstrated significant hyperglycemia, hyperlipidemia, and increased inflammation, oxidative stress, calcification, and finally atherogenesis progression. Treatment of diabetic hyperlipemic rats with, policosanol, omega-3 fatty acids (natural products) and atorvastatin for eight weeks significantly increased high-density lipoprotein cholesterol (HDL-C), Vitamin D, decreased aortic vacuoles number, and inhibited calcification process. Policosanol induced more remarkable reduction in the density and number of foam cells and improved the intimal lesions of the aorta as compared to atorvastatin. Drugs under study exerted hypoglycemic effect along with an inhibition of inflammation, oxidative stress, and calcium deposition with certain variations but policosanol effect was remarkable in comparison with other drugs. © 2016 by the Society for Experimental Biology and Medicine.
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Gerhard, Glenn S.; Styer, Amanda M.; Wood, G. Craig; Roesch, Stephen L.; Petrick, Anthony T.; Gabrielsen, Jon; Strodel, William E.; Still, Christopher D.; Argyropoulos, George
2013-01-01
OBJECTIVE Roux-en-Y gastric bypass (RYGB) in humans can remit type 2 diabetes, but the operative mechanism is not completely understood. In mice, fibroblast growth factor (FGF) 15 (FGF19 in humans) regulates hepatic bile acid (BA) production and can also resolve diabetes. In this study, we tested the hypothesis that the FGF19–BA pathway plays a role in the remission of human diabetes after RYGB surgery. RESEARCH DESIGN AND METHODS Cohorts of diabetic and nondiabetic individuals of various body weights were used. In addition, RYGB patients without diabetes (No-Diabetes), RYGB patients with diabetes who experienced remission for at least 12 months after surgery (Diabetes-R), and RYGB patients with diabetes who did not go into remission after surgery (Diabetes-NoR) were studied. Circulating FGF19 and BA levels, hepatic glycogen content, and expression levels of genes regulating the FGF19–BA pathway were compared among these groups of patients using pre- and postoperative serum samples and intraoperative liver biopsies. RESULTS Preoperatively, patients with diabetes had lower FGF19 and higher BA levels than nondiabetic patients, irrespective of body weight. In diabetic patients undergoing RYGB, lower FGF19 levels were significantly correlated with increased hepatic expression of the cholesterol 7alpha-hydroxylase 1 (CYP7A1) gene, which modulates BA production. Following RYGB surgery, however, FGF19 and BA levels (particularly cholic and deoxycholic acids) exhibited larger increases in Diabetic-R patients compared with nondiabetic and Diabetic-NoR patients. CONCLUSIONS Taken together, the baseline and postoperative data implicate the FGF19–CYP7A1–BA pathway in the etiology and remission of type 2 diabetes following RYGB surgery. PMID:23801799
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Elkins, Christopher A.; Savage, Dwayne C.
1998-01-01
Cytosolic extracts of Lactobacillus johnsonii 100-100 (previously reported as Lactobacillus sp. strain 100-100) contain four heterotrimeric isozymes composed of two peptides, α and β, with conjugated bile salt hydrolase (BSH) activity. We now report cloning, from the genome of strain 100-100, a 2,977-bp DNA segment that expresses BSH activity in Escherichia coli. The sequencing of this segment showed that it contained one complete and two partial open reading frames (ORFs). The 3′ partial ORF (927 nucleotides) was predicted by BLAST and confirmed with 5′ and 3′ deletions to be a BSH gene. Thermal asymmetric interlaced PCR was used to extend and complete the 948-nucleotide sequence of the BSH gene 3′ of the cloned segment. The predicted amino acid sequence of the 5′ partial ORF (651 nucleotides) was about 80% similar to the C-terminal half of the largest, complete ORF (1,353 nucleotides), and these two putative proteins were similar to several amine, multidrug resistance, and sugar transport proteins of the major facilitator superfamily. E. coli DH5α cells transformed with a construct containing these ORFs, in concert with an extracellular factor produced by strain 100-100, demonstrated levels of uptake of [14C]taurocholic acid that were increased as much as threefold over control levels. [14C]Cholic acid was taken up in similar amounts by strain DH5α pSportI (control) and DH5α p2000 (transport clones). These findings support a hypothesis that the ORFs are conjugated bile salt transport genes which may be arranged in an operon with BSH genes. PMID:9721268
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NASA Astrophysics Data System (ADS)
Ng, Khen Eng; Amin, Mohd Cairul Iqbal Mohd; Katas, Haliza; Amjad, Muhammad Wahab; Butt, Adeel Masood; Kesharwani, Prashant; Iyer, Arun K.
2016-12-01
This study developed novel triblock pH-responsive polymeric micelles (PMs) using cholic acid-polyethyleneimine-poly- l-arginine (CA-PEI-pArg) copolymers. PEI provided pH sensitivity, while the hydrophilic cell-penetrating pArg peptide promoted cellular PM internalization. The copolymers self-assembled into PMs in aqueous solution at above the critical micelle concentration (2.98 × 10-7 M) and encapsulated doxorubicin in the core region, with a 34.2% ( w/ w) entrapment efficiency. PMs showed pH-dependent swelling, increasing in size by almost sevenfold from pH 7.4 to 5.0. Doxorubicin release was pH-dependent, with about 65% released at pH 5.0, and 32% at pH 7.4. Cellular uptake, assessed by confocal microscopy and flow cytometry, was enhanced by using doxorubicin-loaded CA-PEI-pArg PMs, as compared to free doxorubicin and DOX-loaded CA-PEI PMs. Moreover, 24-h incubation of these PMs with a human breast cancer cell line produced greater cytotoxicity than free doxorubicin. These results indicate that pH-responsive CA-PEI-pArg micelles could provide a versatile delivery system for targeted cancer therapy using hydrophobic drugs.
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Mohana, Thiruchenduran; Navin, Alukkathara Vijayan; Jamuna, Sanker; Sakeena Sadullah, Mohammed Sadullah; Niranjali Devaraj, Sivasithamparam
2015-08-01
Monocyte to macrophage differentiation is a key event in the progression of atherosclerosis. An understanding on the fundamental molecular mechanisms and the identification of regulatory mechanisms behind this differentiation may aid in the identification of new therapeutic strategies. Inhibition of this phenomenon will form first line of defense in the prevention and treatment of atherosclerosis. In the current study we explored hypercholesterolemia induced monocyte to macrophage differentiation in-vivo (Wistar rats) leading to atherosclerosis and OxyLDL, M-CSF induced monocyte differentiation in-vitro (U937 cells). Oligomeric proanthocyanidin (OPC) isolated from Crataegus oxyacantha was tested for its efficacy in downregulating this differentiation and in preventing atherogenic disturbances. Cholesterol cholic acid diet induced an increased monocyte to macrophage differentiation by upregulating MCP1 and VCAM1 which induced the inflammatory cytokines that further substantiated the monocyte conversion and infiltration into the vascular walls. On addition of OxyLDL and M-CSF to U937 cells, macrophage markers CD36 and CD 68, PPARγ, MMP2 and 9 were elevated, suggesting differentiation. OPC downregulated this differentiation and thus could prevent the initiation of atherosclerosis. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Akila, Manickam; Devaraj, Halagowder
2008-01-01
This study was designed to address the synergistic effect of tincture of Crataegus (TCR) and Mangifera indica L. (MNG) extracts on the lipid and antioxidant parameters in the development of aortic lesions in diet-induced atherosclerosis in rats. TCR, is an alcoholic extract made from the berries of Hawthorn, Crataegus oxyacantha with flavanoids as the main constituent. MNG, is an alcoholic extract made from the stem bark of Mangifera indica L. with polyphenols as the main constituent. Simultaneous oral administration of these two extracts (0.5 ml/100 g body weight) to rats fed with an atherogenic (4% cholesterol, 1% cholic acid, 0.5% thiouracil) diet prevented the elevation of lipids in the serum and heart and also caused a significant decrease in lipid accumulation in the liver and aorta reverting the hyperlipidaemic condition of these rats. These extracts significantly restored the activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione, thereby restoring the antioxidant status of the organism to almost normal levels. This effect could be attributed to the synergistic activity of flavonoids in TCR and polyphenols of MNG.
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Mitamura, Kuniko; Sakai, Toshihiro; Nakai, Risa; Wakamiya, Tateaki; Iida, Takashi; Hofmann, Alan F; Ikegawa, Shigeo
2011-06-01
Previous work from this laboratory has reported the chemical synthesis of N-acetylcysteine (NAC) conjugates of natural bile acids (BAs) and shown that such novel conjugates can be formed in vivo in rats to which NAC has been administered. The subsequent fate of such novel conjugates is not known. One possible biotransformation is sulfation, a major pathway for BAs N-acylamidates in patients with cholestatic liver disease. Here, we report the chemical synthesis of the 3-sulfates of the S-acyl NAC conjugates of five natural BAs (cholic, chenodeoxycholic, deoxycholic, ursodeoxycholic, and lithocholic). We also measured the sulfation of N-acetylcysteine-natural bile acid (BA-NAC) conjugates when they were incubated with a rat liver cytosolic fraction. The chemical structures of the BA-NAC 3-sulfates were confirmed by proton nuclear magnetic resonance, as well as by means of electrospray ionization-linear ion trap mass spectrometry with negative-ion detection. Upon collision-induced dissociation of singly and doubly charged deprotonated molecules, structurally informative product ions were observed. Using a triple-stage quadrupole instrument, selected reaction monitoring analyses by monitoring characteristic transition ions allowed the achievement of a highly sensitive and specific assay. When BA-NACs were incubated with a rat liver cytosolic fraction to which 3'-phosphoadenosine 5'-phosphosulfate was added, sulfation occurred, but the dominant reaction was hydrolysis of the S-acyl linkage to form the unconjugated BAs. Subsequent sulfation occurred at C-3 on the unconjugated BAs that had been formed from the BA-NACs. Such sulfation was proportional to the hydrophobicity of the unconjugated bile acid. Thus, NAC conjugates of BAs as well as their C-3 sulfates if formed in vivo are rapidly hydrolyzed by cytosolic enzymes.
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Bouscarel, B; Fromm, H; Ceryak, S; Cassidy, M M
1991-01-01
Ursodeoxycholic acid (UDCA), in contrast to both chenodeoxycholic acid (CDCA), its 7 alpha-epimer, and lithocholic acid, enhanced receptor-dependent low-density lipoprotein (LDL) uptake and degradation in isolated hamster hepatocytes. The increase in cell-associated LDL was time- and concentration-dependent, with a maximum effect observed at approx. 60 min with 1 mM-UDCA. This increase was not associated with a detergent effect of UDCA, as no significant modifications were observed either in the cellular release of lactate dehydrogenase or in Trypan Blue exclusion. The effect of UDCA was not due to a modification of the LDL particle, but rather was receptor-related. UDCA (1 mM) maximally increased the number of 125I-LDL-binding sites (Bmax.) by 35%, from 176 to 240 ng/mg of protein, without a significant modification of the binding affinity. Furthermore, following proteolytic degradation of the LDL receptor with Pronase, specific LDL binding decreased to the level of non-specific binding, and the effect of UDCA was abolished. Conversely, the trihydroxy 7 beta-hydroxy bile acid ursocholic acid and its 7 alpha-epimer, cholic acid, induced a significant decrease in LDL binding by approx. 15%. The C23 analogue of UDCA (nor-UDCA) and CDCA did not affect LDL binding. On the other hand, UDCA conjugated with either glycine (GUDCA) or taurine (TUDCA), increased LDL binding to the same extent as did the free bile acid. The half maximum time (t1/2) to reach the full effect was 1-2 min for UDCA and TUDCA, while GUDCA had a much slower t1/2 of 8.3 min. Ketoconazole (50 microM), an antifungal agent, increased LDL binding, but this effect was not additive when tested in the presence of 0.7 mM-UDCA. The results of the studies indicate that, in isolated hamster hepatocytes, the UDCA-induced increase in receptor-dependent LDL binding and uptake represents a direct effect of this bile acid. The action of the bile acid is closely related to its specific structural conformation, since UDCA and its conjugates are the only bile acids shown to express this ability thus far. However, certain agents other than bile acids, such as ketoconazole, have a similar effect. Finally, the studies suggest that the recruitment of LDL receptors from a latent pool in the hepatocellular membrane may be the mechanism by which UDCA exerts its direct effect. Images Fig. 6. PMID:1764022
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Frisch, Kim; Stimson, Damion H R; Venkatachalam, Taracad; Pierens, Gregory K; Keiding, Susanne; Reutens, David; Bhalla, Rajiv
2018-05-04
Enterohepatic circulation (EHC) of conjugated bile acids is an important physiological process crucial for regulation of intracellular concentrations of bile acids and their function as detergents and signal carriers. Only few bile acid-derived imaging agents have been synthesized and hitherto none have been evaluated for studies of EHC. We hypothesized that N-(4-[ 18 F]fluorobenzyl)cholylglycine ([ 18 F]FBCGly), a novel fluorine-18 labeled derivative of endogenous cholylglycine, would be a suitable tracer for PET of the EHC of conjugated bile acids, and we report here a radiosynthesis of [ 18 F]FBCGly and a proof-of-concept study by PET/MR in rats. A radiosynthesis of [ 18 F]FBCGly was developed based on reductive alkylation of glycine with 4-[ 18 F]fluorobenzaldehyde followed by coupling to cholic acid. [ 18 F]FBCGly was investigated in vivo by dynamic PET/MR in anesthetized rats; untreated or treated with cholyltaurine or rifampicin. Possible in vivo metabolites of [ 18 F]FBCGly were investigated by analysis of blood and bile samples, and the stability of [ 18 F]FBCGly towards enzymatic de-conjugation by Cholylglycine Hydrolase was tested in vitro. [ 18 F]FBCGly was produced with a radiochemical purity of 96% ± 1% and a non-decay corrected radiochemical yield of 1.0% ± 0.3% (mean ± SD; n = 12). PET/MR studies showed that i.v.-administrated [ 18 F]FBCGly underwent EHC within 40-60 min with a rapid transhepatic transport from blood to bile. In untreated rats, the radioactivity concentration of [ 18 F]FBCGly was approximately 15 times higher in bile than in liver tissue. Cholyltaurine and rifampicin inhibited the biliary secretion of [ 18 F]FBCGly. No fluorine-18 metabolites of [ 18 F]FBCGly were observed. We have developed a radiosynthesis of a novel fluorine-18 labeled bile acid derivative, [ 18 F]FBCGly, and shown by PET/MR that [ 18 F]FBCGly undergoes continuous EHC in rats without metabolizing. This novel tracer may prove useful in PET studies on the effect of drugs or diseases on the EHC of conjugated bile acids. Copyright © 2018 Elsevier Inc. All rights reserved.
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Shibata, Shinya; Hayakawa, Kazuhito; Egashira, Yukari; Sanada, Hiroo
2007-01-16
Nuclear receptors are involved in regulating the expression of cholesterol 7alpha-hydroxylase (CYP7A1), however, their roles in the up-regulation of CYP7A1 by cholestyramine (CSR) are still unclear. In the present study, male Wistar rats were divided into four groups and fed [high sucrose + 10% lard diet] (H), [H + 3% CSR diet] (H + CSR), [H + 0.5% cholesterol + 0.25% sodium cholate diet] (C), or [C + 3% CSR diet] (C + CSR) for 2 weeks. Cholestyramine decreased serum and liver cholesterol levels significantly in rats fed C-based diets, but had no effect on these parameters in rats fed H-based diets. Cholestyramine raised hepatic levels of CYP7A1 mRNA and activity in both groups. The gene expression of hepatic ATP-binding cassettes A1 and G5, regulated by liver X receptor (LXR), were unchanged and down-regulated by cholestyramine, respectively. The mRNA levels of the hepatic ATP-binding cassette B11 and short heterodimer partner (SHP), regulated by farnesoid X receptor (FXR), were not changed by cholestyramine. C-based diets, which contained cholesterol and cholic acid, increased SHP mRNA levels compared to H-based diets. Consequently, in rats fed the C+CSR diet, hepatic FXR was activated by dietary bile acids, but the hepatic CYP7A1 mRNA level was increased 16-fold compared to that in rats fed an H diet. These results suggest that cholestyramine up-regulates the expression of CYP7A1 independently via LXR- or FXR-mediated pathways in rats.
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Multiple copies of a bile acid-inducible gene in Eubacterium sp. strain VPI 12708.
Gopal-Srivastava, R; Mallonee, D H; White, W B; Hylemon, P B
1990-01-01
Eubacterium sp. strain VPI 12708 is an anaerobic intestinal bacterium which possesses inducible bile acid 7-dehydroxylation activity. Several new polypeptides are produced in this strain following induction with cholic acid. Genes coding for two copies of a bile acid-inducible 27,000-dalton polypeptide (baiA1 and baiA2) have been previously cloned and sequenced. We now report on a gene coding for a third copy of this 27,000-dalton polypeptide (baiA3). The baiA3 gene has been cloned in lambda DASH on an 11.2-kilobase DNA fragment from a partial Sau3A digest of the Eubacterium DNA. DNA sequence analysis of the baiA3 gene revealed 100% homology with the baiA1 gene within the coding region of the 27,000-dalton polypeptides. The baiA2 gene shares 81% sequence identity with the other two genes at the nucleotide level. The flanking nucleotide sequences associated with the baiA1 and baiA3 genes are identical for 930 bases in the 5' direction from the initiation codon and for at least 325 bases in the 3' direction from the stop codon, including the putative promoter regions for the genes. An additional open reading frame (occupying from 621 to 648 bases, depending on the correct start codon) was found in the identical 5' regions associated with the baiA1 and baiA3 clones. The 5' sequence 930 bases upstream from the baiA1 and baiA3 genes was totally divergent. The baiA2 gene, which is part of a large bile acid-inducible operon, showed no homology with the other two genes either in the 5' or 3' direction from the polypeptide coding region, except for a 15-base-pair presumed ribosome-binding site in the 5' region. These studies strongly suggest that a gene duplication (baiA1 and baiA3) has occurred and is stably maintained in this bacterium. Images PMID:2376563
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Wang, Yong; Yu, Xing; Zhao, Qun-zi; Zheng, Shu; Qing, Wen-jie; Miao, Chun-di; Sanjay, Jaiswal
2016-01-01
We have investigated comprehensively the effects of thyroid function on gallstone formation in a mouse model. Gonadectomized gallstone-susceptible male C57BL/6 mice were randomly distributed into three groups each of which received an intervention to induce hyperthyroidism, hypothyroidism, or euthyroidism. After 5 weeks of feeding a lithogenic diet of 15% (w/w) butter fat, 1% (w/w) cholesterol, and 0.5% (w/w) cholic acid, mice were killed for further experiments. The incidence of cholesterol monohydrate crystal formation was 100% in mice with hyperthyroidism, 83% in hypothyroidism, and 33% in euthyroidism, the differences being statistically significant. Among the hepatic lithogenic genes, Trβ was found to be up-regulated and Rxr down-regulated in the mice with hypothyroidism. In contrast, Lxrα, Rxr, and Cyp7α1 were up-regulated and Fxr down-regulated in the mice with hyperthyroidism. In conclusion, thyroid dysfunction, either hyperthyroidism or hypothyroidism, promotes the formation of cholesterol gallstones in C57BL/6 mice. Gene expression differences suggest that thyroid hormone disturbance leads to gallstone formation in different ways. Hyperthyroidism induces cholesterol gallstone formation by regulating expression of the hepatic nuclear receptor genes such as Lxrα and Rxr, which are significant in cholesterol metabolism pathways. However, hypothyroidism induces cholesterol gallstone formation by promoting cholesterol biosynthesis. PMID:27381728
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Wang, Yong; Yu, Xing; Zhao, Qun-Zi; Zheng, Shu; Qing, Wen-Jie; Miao, Chun-di; Sanjay, Jaiswal
2016-07-01
We have investigated comprehensively the effects of thyroid function on gallstone formation in a mouse model. Gonadectomized gallstone-susceptible male C57BL/6 mice were randomly distributed into three groups each of which received an intervention to induce hyperthyroidism, hypothyroidism, or euthyroidism. After 5 weeks of feeding a lithogenic diet of 15% (w/w) butter fat, 1% (w/w) cholesterol, and 0.5% (w/w) cholic acid, mice were killed for further experiments. The incidence of cholesterol monohydrate crystal formation was 100% in mice with hyperthyroidism, 83% in hypothyroidism, and 33% in euthyroidism, the differences being statistically significant. Among the hepatic lithogenic genes, Trβ was found to be up-regulated and Rxr down-regulated in the mice with hypothyroidism. In contrast, Lxrα, Rxr, and Cyp7α1 were up-regulated and Fxr down-regulated in the mice with hyperthyroidism. In conclusion, thyroid dysfunction, either hyperthyroidism or hypothyroidism, promotes the formation of cholesterol gallstones in C57BL/6 mice. Gene expression differences suggest that thyroid hormone disturbance leads to gallstone formation in different ways. Hyperthyroidism induces cholesterol gallstone formation by regulating expression of the hepatic nuclear receptor genes such as Lxrα and Rxr, which are significant in cholesterol metabolism pathways. However, hypothyroidism induces cholesterol gallstone formation by promoting cholesterol biosynthesis.
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Biomolecular signatures of diabetic wound healing by structural mass spectrometry
Hines, Kelly M.; Ashfaq, Samir; Davidson, Jeffrey M.; Opalenik, Susan R.; Wikswo, John P.; McLean, John A.
2013-01-01
Wound fluid is a complex biological sample containing byproducts associated with the wound repair process. Contemporary techniques, such as immunoblotting and enzyme immunoassays, require extensive sample manipulation and do not permit the simultaneous analysis of multiple classes of biomolecular species. Structural mass spectrometry, implemented as ion mobility-mass spectrometry (IM-MS), comprises two sequential, gas-phase dispersion techniques well suited for the study of complex biological samples due to its ability to separate and simultaneously analyze multiple classes of biomolecules. As a model of diabetic wound healing, polyvinyl alcohol (PVA) sponges were inserted subcutaneously into non-diabetic (control) and streptozotocin-induced diabetic rats to elicit a granulation tissue response and to collect acute wound fluid. Sponges were harvested at days 2 or 5 to capture different stages of the early wound healing process. Utilizing IM-MS, statistical analysis, and targeted ultra-performance liquid chromatography (UPLC) analysis, biomolecular signatures of diabetic wound healing have been identified. The protein S100-A8 was highly enriched in the wound fluids collected from day 2 diabetic rats. Lysophosphatidylcholine (20:4) and cholic acid also contributed significantly to the differences between diabetic and control groups. This report provides a generalized workflow for wound fluid analysis demonstrated with a diabetic rat model. PMID:23452326
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Matsui, Ryoichi; Uchida, Noriyuki; Ohtani, Masataka; Yamada, Kuniyo; Shigeta, Arisu; Kawamura, Izuru; Aida, Takuzo; Ishida, Yasuhiro
2016-12-05
Five novel surfactants were prepared by modifying the three hydroxy groups of sodium cholate with triethylene glycol chains endcapped with an amide (SC-C 1 , SC- n C 4 , and SC- n C 5 ) or a carbamoyl group (SC-O n C 4 and SC-O t C 4 ). The phase behavior of aqueous mixtures of these surfactants with 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) was systematically studied by 31 P NMR spectroscopy. The surfactants endcapped with carbamate groups (SC-O n C 4 and SC-O t C 4 ) formed magnetically alignable bicelles over unprecedentedly wide ranges of conditions, in terms of temperature (from 21-23 to >90 °C), lipid/surfactant ratio (from 5 to 8), total lipid content (5-20 wt %), and lipid type [DMPC, 1,2-dilauroyl-sn-glycero-3-phosphatidylcholine (DLPC), or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC)]. In conjunction with appropriate phospholipids, the carbamate-endcapped surfactants afforded unique bicelles, characterized by exceptional thermal stabilities (from 0 to >90 °C), biomimetic lipid compositions (DMPC/POPC=25:75 to 50:50), and extremely large 2 H quadrupole splittings (up to 71 Hz). © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Growth hormone resistance exacerbates cholestasis-induced murine liver fibrosis
Stiedl, Patricia; McMahon, Robert; Blaas, Leander; Stanek, Victoria; Svinka, Jasmin; Grabner, Beatrice; Zollner, Gernot; Kessler, Sonja M.; Claudel, Thierry; Müller, Mathias; Mikulits, Wolfgang; Bilban, Martin; Esterbauer, Harald; Eferl, Robert; Haybaeck, Johannes; Trauner, Michael; Casanova, Emilio
2016-01-01
Growth hormone (GH) resistance has been associated with liver cirrhosis in humans but its contribution to the disease remains controversial. In order to elucidate whether GH resistance plays a causal role in the establishment and development of liver fibrosis, or rather represents a major consequence thereof, we challenged mice lacking the Growth hormone receptor gene (Ghr-/-, a model for GH resistance) by crossing them with Mdr2 knockout mice (Mdr2-/-), a mouse model of inflammatory cholestasis and liver fibrosis. Ghr-/-;Mdr2-/- mice showed elevated serum markers associated with liver damage and cholestasis, extensive bile duct proliferation and increased collagen deposition relative to Mdr2 -/- mice, thus suggesting a more severe liver fibrosis phenotype. Additionally, Ghr-/-;Mdr2-/- mice had a pronounced down-regulation of hepato-protective genes Hnf6, Egfr and Igf-1, and significantly increased levels of ROS and apoptosis in hepatocytes, compared to control mice. Moreover, single knockout mice (Ghr-/-) fed with a diet containing 1% cholic acid displayed an increase in hepatocyte ROS production, hepatocyte apoptosis and bile infarcts compared to their wildtype littermates, indicating that loss of Ghr renders hepatocytes more susceptible to toxic bile acid accumulation. Surprisingly, and despite their severe fibrotic phenotype, Ghr-/-;Mdr2-/- mice displayed a significant decrease in tumour incidence compared to Mdr2-/- mice, indicating that loss of Ghr signaling may slow the progression from fibrosis/cirrhosis to cancer in the liver. Conclusion Our findings suggest that GH resistance dramatically exacerbates liver fibrosis in a mouse model of inflammatory cholestasis, therefore suggesting that GH resistance plays a causal role in the disease and provides a novel target for the development of liver fibrosis treatments. PMID:25179284
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NASA Astrophysics Data System (ADS)
Narayana Kalkura, S.; Natarajan, Subramanian
Among the various crystallization techniques, crystallization in gels has found wide applications in the fields of biomineralization and macromolecular crystallization in addition to crystallizing materials having nonlinear optical, ferroelectric, ferromagnetic, and other properties. Furthermore, by using this method it is possible to grow single crystals with very high perfection that are difficult to grow by other techniques. The gel method of crystallization provides an ideal technique to study crystal deposition diseases, which could lead to better understanding of their etiology. This chapter focuses on crystallization in gels of compounds that are responsible for crystal deposition diseases. The introduction is followed by a description of the various gels used, the mechanism of gelling, and the fascinating phenomenon of Liesegang ring formation, along with various gel growth techniques. The importance and scope of study on crystal deposition diseases and the need for crystal growth experiments using gel media are stressed. The various crystal deposition diseases, viz. (1) urolithiasis, (2) gout or arthritis, (3) cholelithiasis and atherosclerosis, and (4) pancreatitis and details regarding the constituents of the crystal deposits responsible for the pathological mineralization are discussed. Brief accounts of the theories of the formation of urinary stones and gallstones and the role of trace elements in urinary stone formation are also given. The crystallization in gels of (1) the urinary stone constituents, viz. calcium oxalate, calcium phosphates, uric acid, cystine, etc., (2) the constituents of the gallstones, viz. cholesterol, calcium carbonate, etc., (3) the major constituent of the pancreatic calculi, viz., calcium carbonate, and (4) cholic acid, a steroidal hormone are presented. The effect of various organic and inorganic ions, trace elements, and extracts from cereals, herbs, and fruits on the crystallization of major urinary stone and gallstone constituents are described. In addition, tables of gel-grown organic and inorganic crystals are provided.
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Metformin treatment prevents gallstone formation but mimics porcelain gallbladder in C57Bl/6 mice.
Dorvash, Mohammad Reza; Khoshnood, Mohammad Javad; Saber, Hossein; Dehghanian, Amirreza; Mosaddeghi, Pouria; Firouzabadi, Negar
2018-06-05
Gallstone disease (GD) is highly correlated with metabolic syndrome and its related illnesses including type II diabetes (DMII) and polycystic ovary syndrome (PCOS). While previous studies claimed that metformin decreases the chance of developing GD in PCOS patients, this phenomenon has not been investigated in animal models to date. Here we fed a high fat diet (HFD) containing 2% of cholesterol and 1% of cholic acid to ten-week-old male C57Bl/6 mice for 105 days. The groups were as follows: Low fat diet; HFD; HFD + Ursodeoxycholic acid (UDCA) (day 1-105); HFD + Metformin (day 1-105); HFD + Metformin (Met) (day 64-105). All drugs were administered by oral gavage (Met = 300 mg/kg & UDCA = 750 mg/kg). Serum lipid profile and gross organ examination were performed after euthanasia. A microscopic evaluation of the paraffin-embedded gallbladders was done after hematoxylin & eosin and Von Kossa staining. HFD successfully induces gallstone (4 out of 4 of the HFD members). While both UDCA and metformin (d 1-105) prevented gallstone formation and cholecystitis, Metformin (d 64-105) group had a few small stones. Additionally, metformin induces mucosal calcification in gallbladder (porcelain GB) of more than 80% of the HFD + Met (day 1-105) and HFD + Met (day 64-105) groups, collectively, which can be a potential problem by itself. While metformin shows a noticeable benefit towards GB health by reducing the chance for gallstone formation, if it induces porcelain gallbladder in humans as well, it might inflict patients with preventable medical charges. Copyright © 2018 Elsevier B.V. All rights reserved.
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Kamesh, Venkatakrishnan; Sumathi, Thangarajan
2014-10-01
Bacopa monniera L. (Scrophulariaceae) is used as a traditional medicine in India for various ailments such as epilepsy, mental disorders, and also as a cardio-tonic. However, its nephroprotective role is still unknown. The present study assesses the modulatory impact of the alcoholic (ethanol) extract of Bacopa monniera (AEBM) on renal oxido-lipidemic stress in hypercholesterolemic rats. B. monniera (1 kg) was extracted with 90% ethanol, filtered, and dried (52 g). Group-I rats as control, Group-II rats fed with a hypercholesterolemic diet (HCD) for 45 d [4% cholesterol and 1% cholic acid], Group-III rats fed with HCD for 45 d + AEBM (40 mg/kg, body weight) for last 30 d, and Group-IV AEBM alone rats. Blood and kidney were removed to analyze lipid, antioxidant status, and histological analysis. The levels of total cholesterol (TC), triacylglycerol (TG), phospholipids (PLs), renal functional parameters (urea, creatinine, and uric acid), and lipid peroxidation (LPO) products were significantly attenuated (p < 0.01) in AEBM-treated hypercholesterolemic rats. Activities of both enzymic (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR)) and non-enzymic antioxidant (GSH, Vit-C, and Vit-E) were significantly increased (p < 0.01), on supplementation with AEBM. Administration with AEBM the mRNA levels of eNOS and iNOS genes was significantly up-regulated and down-regulated (p < 0.01). Histomorphological observations also evidenced that AEBM effectively protects the kidney from hypercholesterolemia-mediated oxido-lipidemic damage. From this study, we hypothesized that AEBM can act as renoprotective agent by attenuating the renal oxido-lipidemic stress via regulating NOS level and thereby protects the nephron in hypercholesterolemic rats.
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Macias, R I; Monte, M J; El-Mir, M Y; Villanueva, G R; Marin, J J
1998-09-01
Rat liver uptake and bile output of the cytostatic complex cis-diammineplatinum(II)-chlorocholylglycinate (Bamet-R2) were studied. Up to 100 microM, Bamet-R2 uptake by rat hepatocytes in primary culture followed saturation kinetics (Vmax = 0.65 +/- 0.12 nmol/5 min per mg protein; K(M) = 45.2 +/- 10.7 microM). Bamet-R2 uptake was lower than that of cholylglycinate (CG) but higher than that of cisplatin. Replacement of 116 mM NaCl by 116 mM choline chloride did not significantly reduce Bamet-R2 uptake. Addition of 500 microM CG, cholic acid, estrone sulfate, or ouabain to 50 microM Bamet-R2-containing incubation media inhibited Bamet-R2 uptake. No liver biotransformation of Bamet-R2 occurred, as indicated by HPLC analysis of bile collected from anesthetized rats after intravenous administration of the drug. Bamet-R2 uptake and secretion into bile by isolated rat livers exceeded those of cisplatin but were lower than those of CG. Differences between Bamet-R2 and CG were more marked for bile output than for liver uptake. Thus, higher Bamet-R2 than CG or cisplatin liver content was found. Co-administration of Bamet-R2 and CG revealed that CG induced a slight reduction in Bamet-R2 uptake and a marked inhibition in Bamet-R2 bile output. By contrast, Bamet-R2 had no effect on CG on either liver uptake or bile output. In sum, the present data indicate that Bamet-R2 is efficiently taken up and secreted into bile by the rat liver by mechanisms shared in part by natural bile acids.
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Sakuradani, Eiji; Kobayashi, Michihiko; Shimizu, Sakayu
1999-01-01
Based on the sequence information for bovine and yeast NADH-cytochrome b5 reductases (CbRs), a DNA fragment was cloned from Mortierella alpina 1S-4 after PCR amplification. This fragment was used as a probe to isolate a cDNA clone with an open reading frame encoding 298 amino acid residues which show marked sequence similarity to CbRs from other sources, such as yeast (Saccharomyces cerevisiae), bovine, human, and rat CbRs. These results suggested that this cDNA is a CbR gene. The results of a structural comparison of the flavin-binding β-barrel domains of CbRs from various species and that of the M. alpina enzyme suggested that the overall barrel-folding patterns are similar to each other and that a specific arrangement of three highly conserved amino acid residues (i.e., arginine, tyrosine, and serine) plays a role in binding with the flavin (another prosthetic group) through hydrogen bonds. The corresponding genomic gene, which was also cloned from M. alpina 1S-4 by means of a hybridization method with the above probe, had four introns of different sizes. These introns had GT at the 5′ end and AG at the 3′ end, according to a general GT-AG rule. The expression of the full-length cDNA in a filamentous fungus, Aspergillus oryzae, resulted in an increase (4.7 times) in ferricyanide reduction activity involving the use of NADH as an electron donor in the microsomes. The M. alpina CbR was purified by solubilization of microsomes with cholic acid sodium salt, followed by DEAE-Sephacel, Mono-Q HR 5/5, and AMP-Sepharose 4B affinity column chromatographies; there was a 645-fold increase in the NADH-ferricyanide reductase specific activity. The purified CbR preferred NADH over NADPH as an electron donor. This is the first report of an analysis of this enzyme in filamentous fungi. PMID:10473389
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Qin, Ling; Mills, Denise A.; Hiser, Carrie; Murphree, Anna; Garavito, R. Michael; Ferguson-Miller, Shelagh; Hosler, Jonathan
2008-01-01
Cytochrome c oxidase (CcO) transfers protons from the inner surface of the enzyme to the buried O2 reduction site through two different pathways, termed K and D, and from the outer surface via an undefined route. These proton paths can be inhibited by metals such as zinc or cadmium, but the sites of inhibition have not been established. Anomalous difference Fourier analyses of Rhodobacter sphaeroides CcO crystals, with cadmium added, reveal metal binding sites that include the proposed initial proton donor/acceptor of the K pathway, Glu-101 of subunit II. Mutant forms of CcO that lack Glu-101II (E101A and E101A/H96A) exhibit low activity and eliminate metal binding at this site. Significant activity is restored to E101A and E101A/H96A by adding the lipophilic carboxylic compounds, arachidonic acid and cholic acid, but not by their non-carboxylic analogues. These amphipathic acids likely provide their carboxylic groups as substitute proton donors/acceptors in the absence of Glu-101II, as previously observed for arachidonic acid in mutants that alter Asp-132I of the D pathway. The activity of E101A/H96A is still inhibited by zinc, but this remaining inhibition is nearly eliminated by removal of subunit III, which is known to alter the D pathway. The results identify the Glu-101/His-96 site of subunit II as the site of metal binding that inhibits the uptake of protons into the K pathway and indicate that subunit III contributes to zinc binding and/or inhibition of the D pathway. By removing subunit III from E101A/H96A, thereby eliminating zinc inhibition of the uptake of protons from the inner surface of CcO, we confirm that an external zinc binding site is involved in inhibiting the backflow of protons to the active site. PMID:17477548
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Wilson, T A; Romano, C; Liang, J; Nicolosi, R J
1998-08-01
Cholazol H (Alpha-Beta Technology, Worcester, MA), a chemically functionalized, insoluble dietary fiber with bile acid sequestrant properties, was studied in 30 male F1 B Golden Syrian hamsters for its effect on plasma lipid concentrations and early atherogenesis in experiment 1. In experiment 2, 30 male Golden Syrian hamsters were studied for the effects on plasma lipids and fecal excretion of bile acids. In experiment 1, three groups of 10 hamsters each were fed a chow-based hypercholesterolemic diet supplemented with 5% coconut oil and 0.1% cholesterol for 6 weeks. After 6 weeks, hamsters were continued on the diet with either 0% drug (hypercholesterolemic diet [HCD]), 0.5% cholestyramine (CSTY), or 0.5% Cholazol H for 8 weeks. Fasting plasma lipids were measured at weeks 6, 10, and 14, and early atherosclerosis (fatty streak formation) was measured at week 14. Relative to HCD, CSTY and Cholazol H significantly lowered plasma total cholesterol (TC) (-37%, P < .03, and -30%, P < .04, respectively) and plasma very-low and low-density lipoprotein-cholesterol (nonHDL-C) (-45%, P < .02, and -36%, P < .03, respectively) with no significant effects on plasma HDL-C or triglycerides (TG). Despite similar reductions in nonHDL-C, only Cholazol H significantly prevented early atherosclerosis (-38%, P < .02) relative to HCD. In experiment 2, three groups of 10 hamsters each were fed a chow-based hypercholesterolemic diet supplemented with 10% coconut oil and 0.05% cholesterol and either 0% drug HCD, 0.5% CSTY, or 0.5% Cholazol H for 4 weeks. Fasting plasma lipids were measured at weeks 2 and 4, and fecal bile acids were measured at week 4. Both Cholazol H and CSTY were equally effective in significantly lowering plasma TC (-16%, P < .003, and -13%, P < .01, respectively) and nonHDL-C (-22%, P < .004, and -18%, P < .02, respectively), with no significant effect on HDL-C and TG relative to HCD. Cholazol H and CSTY produced a significantly greater concentration of fecal total bile acids (39%, P < .001, and 28%, P < .002, respectively) relative to HCD. Also, there was a 48% (P < .002) and 65% (P < .001) greater fecal concentration of cholic acid (CA) for Cholazol H-treated hamsters compared with HCD- and CSTY-treated hamsters, respectively. Cholazol H also significantly increased fecal concentration of deoxycholic acid (DCA; 56%, P < .02) compared with HCD. In summary, Cholazol H is as effective as CSTY for prevention of diet-induced hypercholesterolemia and early atherosclerosis in hamsters.
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Matloub, Azza Abdelmageed; Salama, Alaa Hamed; Aglan, Hadeer Ahmed; AbouSamra, Mona Mahmoud; ElSouda, Sahar Salah Mohamed; Ahmed, Hanaa Hamdy
2018-04-01
Bile salts containing vesicles (bilosomes) represent a portentous vesicular carrier that showed prosperous results in delivering active moieties in the gastrointestinal tract (GIT). In this study, bilosomes were exploited to deliver sulfated polysaccharide-protein complexes of Enteromorpha intestinalis (EHEM) and enhance its activity against hepatocellular carcinoma as well as resist harsh GIT conditions. Bilosomes were prepared using the sodium salt of three different bile acids (cholic, deoxycholic, taurodeoxycholic) and two different nonionic surfactants (Span 40 and 65). The effects of experimental variables were thoroughly studied to obtain an optimum formulation loading EHEM. The selected formulation (EH-Bilo-2) prepared with sodium cholate and Span 65 displayed nano-sized (181.1 ± 16.80 nm) spherical vesicles with reasonable entrapment efficiency (71.60 ± 0.25%) and controlled release properties; and thus was investigated as anti-hepatocarcinogenic candidate for in vivo studies. Treatment of hepatocellular carcinoma (HCC) bearing rats with EH-Bilo-2 experienced significant decrease in serum α-fetoprotein, endoglin, lipocalin-2, and heat shock protein 70 levels vs. the untreated counterparts. Furthermore, the photomicrographs of their liver tissue sections showed focal area of degenerated pleomorphic hepatocytes with fine fibrosis originating from the portal area. Thus, the optimized bilosomal formulation is a promising delegate for tackling hepatocellular carcinoma owing to its powerful anti-cancer and anti-angiogenic activity.
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Venkatesan, Nandini; Devaraj, S Niranjali; Devaraj, H
2003-10-01
Research has focussed on the hypocholesterolemic effects of certain types of dietary fiber such as enhancing conversion of hepatic cholesterol to bile acids or increase in catabolism of low density lipoprotein (LDL) via the apo B,E receptor. The effect of oral administration of a unique fibre cocktail of fenugreek seed powder, guar gum and wheat bran (Fibernat) and its varied effects on some aspects of lipid metabolism and cholesterol homeostasis in rats were examined. Rats were administered Fibernat along with the atherogenic diet containing 1.5 % cholesterol and 0.1 % cholic acid. Amounts of hepatic lipids, hepatic and fecal bile acids and activity of hepatic triglyceride lipase (HTGL) were determined. Transmission electron microscopic examination of the liver tissue and extent of uptake of (125)I-LDL and (125)I-VLDL by the hepatic apo B,E receptor was carried out. Food intake and body weight gain were similar between the 3 different dietary groups. Fibernat intake significantly increased apo B,E receptor expression in rat liver as reflected by an increase in the maximum binding capacity (B(max)) of the apo B,E receptor to (125)I-LDL and (125)I-VLDL. The activity of HTGL was increased by approximately 1.5-fold in Fibernat-fed rats as compared to those fed the atherogenic diet alone. A marked hypocholesterolemic effect was observed. Cholesterol homeostasis was achieved in Fibernat-fed rats. Two possible mechanisms are postulated to be responsible for the observed hypocholesterolemic effect a) an increase in conversion of cholesterol to bile acids and b) possibly by intra-luminal binding which resulted in increased fecal excretion of bile acids and neutral sterols. The resulting reduction in cholesterol content of liver cells coupled with upregulation of hepatic apo B,E receptors and increased clearance of circulating atherogenic lipoproteins-LDL and very low density lipoprotein (LDL and VLDL)-is the main mechanism involved in the hypocholesterolemic effect of Fibernat. The results suggest that Fibernat's effect on plasma LDL concentration is also possibly mediated by increased receptor-mediated catabolism of VLDL. Thus, Fibernat therapy is an effective adjunct to diet therapy and might find potential use in the therapy of hyperlipidemic subjects.
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Juan-García, Ana; Picó, Yolanda; Font, Guillermina
2005-05-06
Two procedures based on solid-phase extraction (SPE) and stir-bar sorptive extraction (SBSE) in combination with micellar electrokinetic chromatography (MEKC)--diode array detection (DAD) were compared for the simultaneous extraction of acrinathrin, bitertanol, cyproconazole, fludioxonil, flutriafol, myclobutanil, pyriproxyfen, and tebuconazole in lettuce, tomato, grape, and strawberry. Selectivity and resolution of the MEKC procedure were studied changing the pH and the molarity of the buffer, the type and the concentration of surfactant, and the methanol content in the mobile phase. A buffer consisting of 6 mM sodium tetraborate decahydrate with 75 mM of cholic acid sodium solution (pH 9.2) gave the best results. Linearity, extraction efficiencies and limits of quantitation (LOQs) of both extraction methods were compared. The recoveries obtained by SPE ranged from 40 to 106% with relative standard deviations (R.S.D.s) from 10 to 19% whereas by the SBSE method, the recoveries were 12-47% and the R.S.D.s 3-17%. The LOQs were much better by SPE (0.2-0.5 mg kg(-1) depending on the processed sample amount) than those obtained by SBSE (1 mg kg(-1) for each compound). Advantages and disadvantages of both procedures are also discussed. As SPE is more robust, rapid, and sensitive than SBSE, its application in combination with MEKC is recommended because provided LOQs below the MRLs established, which is not always attained by SBSE.
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Vázquez-Velasco, Miguel; González-Torres, Laura; García-Fernández, Rosa A; Méndez, María Teresa; Bastida, Sara; Benedí, Juana; González-Muñoz, María José; Sánchez-Muniz, Francisco J
2017-06-01
Glucomannan-enriched squid surimi improves cholesterolemia and liver antioxidant status. The effect of squid surimi enriched with glucomannan or glucomannan plus spirulina on liver and heart structures and cell damage markers was tested in fa/fa rats fed highly saturated-hyper-energetic diets. Animals were fed 70% AIN-93M rodent diet plus six versions of 30% squid surimi for 7 weeks: control (C), glucomannan (G), and glucomannan plus spirulina (GS). The cholesterol-control (HC), cholesterol-glucomannan (HG), and cholesterol-glucomannan plus spirulina (HGS) groups were given similar diets that were enriched with 2% cholesterol and 0.4% cholic acid. G and GS diets versus C diet significantly inhibited weight gain and lowered plasma alanine aminotransferase and aspartate aminotransferase, liver steatosis, lipogranulomas, and total inflammation and alteration scores. The hypercholesterolemic agent significantly increased the harmful effects of the C diet. Liver weight, the hepatosomatic index, all damage markers, and total histological scoring rose for HC versus C (at least P < .05). The addition of glucomannan (HG vs. HC) improved these biomarkers, and non-additional effects from spirulina were observed except for the total liver alteration score. In conclusion, glucomannan and glucomannan plus spirulina blocked the highly saturated-hyper-energetic diet negative effects both with and without added cholesterol. Results suggest the usefulness of including these functional ingredients in fish products.
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Musolino, V; Gliozzi, M; Carresi, C; Maiuolo, J; Mollace, R; Bosco, F; Scarano, F; Scicchitano, M; Maretta, A; Palma, E; Iannone, M; Morittu, V M; Gratteri, S; Muscoli, C; Fini, M; Mollace, V
2017-01-01
Bergamot polyphenolic fraction (BPF) has been shown to positively modulate several mechanisms involved in metabolic syndrome, suggesting its use in therapy. In particular, it is able to induce a significant amelioration of serum lipid profile in hyperlipemic patients at different levels. The purpose of our study was to investigate the effect of BPF on cholesterol absorption physiologically mediated by pancreatic cholesterol ester hydrolase (pCEH). An in vitro activity assay was performed to study the effect of BPF on pCEH, whereas the rate of cholesterol absorption was evaluated through in vivo studies. In particular, male, Sprague-Dawley rats (200225 g) were fed either normal chow or chow supplemented with 0.5% cholic acid, 5.5% peanut oil, and varying amounts of cholesterol (0 to 1.5%). BPF (10 mg/Kg) was daily administrated by means of a gastric gavage to animals fed with lipid supplemented diet for 4 weeks and, at the end of the study, plasma lipids and liver cholesteryl esters were measured in all experimental groups. Our results show that BPF was able to inhibit pCEH activity and this effect was confirmed, in vivo, via detection of lymphatic cholesteryl ester in rats fed with a cholesterol-rich diet. This evidence clarifies a further mechanism responsible for the hypolipemic properties of BPF previously observed in humans, confirming its beneficial effect in the therapy of hypercholesterolemia and in the treatment of metabolic syndrome.
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Kamesh, Venkatakrishnan; Sumathi, Thangarajan
2012-12-01
To explore the effect of alcoholic extract of Bacopa monniera (AEBM) on high cholesterol diet-induced rats. The shade-dried and coarsely powdered whole plant material (Bacopa monniera) was extracted with 90% ethanol, finally filtered and dried in vacuum pump. The experimental rats were divided into 4 groups: control (group-I), Rats fed with hypercholesterolemic diet (HCD) for 45 days [4% cholesterol (w/w) and 1% cholic acid], Rats fed with HCD for 45 days+AEBM (40mg/kg, body weight/day orally) for last 30 days (group-III) and AEBM alone (group-IV). Blood and tissues (Aorta) were removed to ice cold containers for various biochemical and histological analysis. AEBM treatment significantly decreased the levels of TC, TG, PL, LDL, VLDL, atherogenic index, LDL/HDL ratio, and TC/HDL ratio but significantly increased the level of HDL when compared to HCD induced rats. Activities on liver antioxidant status (SOD, CAT, GPx, GR, GST) were significantly raised with concomitant reduction in the level of LPO were obtained in AEBM treated rats when compared to HCD rats. Treatment with AEBM significantly lowered the activity of SGOT, LDH and CPK. Histopathology of aorta of cholesterol fed rat showed intimal thickening and foam cell deposition were noted. These results suggests that AEBM extended protection against various biochemical changes and aortic pathology in hypercholesterolemic rats. Thus the plant may therefore be useful for therapeutic treatment of clinical conditions associated hypercholesterolemia. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.
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Nisar, Jaweria; Mustafa, Imtiaz; Anwar, Haseeb; Sohail, Muhammad Umar; Hussain, Ghulam; Ullah, Muhammad Irfan; Faisal, Muhammad Naeem; Bukhari, Shazia Anwer; Basit, Abdul
2017-01-01
Lentinus edodes is a culinary-medicinal mushroom that has an established history of use in Asian therapies. The mushroom offers well-documented beneficial health effects such as antihypercholesterolemic, antitumor, and antibacterial activities. In this study, dried powder of L. edodes fruiting bodies was used to evaluate immunomodulatory, hepatoprotective, and antioxidant effects in hypercholesterolemic rats. Albino rats (n = 24) were divided into 3 groups: the control (CON) group, the hypercholesterolemia-only group (HCG), and the L. edodes group (LEG). Hypercholesterolemia was induced in rats in the HCG and LEG by feeding cholesterol and cholic acid in a chow maintenance diet (CMD) for 24 days. The CON group was fed the CMD throughout the experiment. The HCG continued on the high-cholesterol diet without any L. edodes supplement. The LEG was fed the high-cholesterol diet supplemented with L. edodes for an additional 42 days. Various biological health biomarkers, such as total antioxidant capacity, total oxidant status, arylesterase, paraoxonase activity, and liver enzymes in serum were studied to evaluate antioxidant and hepatoprotective responses. Cell-mediated immunity was evaluated in each group through a delayed type of hypersensitivity reaction. The total oxidant status decreased significantly (P ≤ 0.05) after administration of L. edodes in the diet. The cell-mediated immune response significantly increased (P ≤ 0.05) in the LEG. The significant decrease in liver enzymes supports the hepatoprotective effect of L. edodes. In conclusion, the results show the immunomodulatory, hepatoprotective, and antioxidant activities of L. edodes supplementation in hypercholesterolemic rats.
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Kosters, Astrid; Felix, Julio C; Desai, Moreshwar S; Karpen, Saul J
2014-02-01
Retinoid X Receptor α (RXRα) is the principal heterodimerization partner of class II Nuclear Receptors (NRs), and a major regulator of gene expression of numerous hepatic processes, including bile acid (BA) homeostasis through multiple partners. Specific contributions of hepatic RXRα domains in heterodimer function in response to either BA load or ductular cholestasis are not fully characterized. Wild-type (WT) mice and mice expressing a hepatocyte-specific RXRα lacking the DNA-Binding-Domain (hs-RxrαΔex4(-/-)), which retains partial ability to heterodimerize with its partners, were fed a 1% cholic acid (CA) diet for 5 days, a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet for 3 weeks, or control diet. Serum ALT (6.5-fold; p<0.05), AST (9.3-fold; p=0.06) and BA (2.8-fold; p<0.05) were increased in CA-fed hs-RxαΔex4(-/-) mice compared to CA-fed WT mice, but were equally induced between genotypes by DDC-feeding. CA-feeding elevated total (4.4-fold; p=0.06) and unconjugated (2.2-fold; p<0.02) bilirubin levels in hs-RxrαΔex4(-/-) mice compared to WT mice, but not in DDC-fed hs-RxrαΔex4(-/-) mice. Increased necrosis and inflammation was observed in CA-fed, but not in DDC-fed hs-RxrαΔex4(-/-) mice. Apoptotic markers DR5, CK8, CK18 RNA were increased in CA- and DDC-fed hs-RxrαΔex4(-/-) mice. Cleaved caspase 3, CK18 and p-JNK protein were elevated in CA-fed but not in DDC-fed hs-RxrαΔex4(-/-) mice. Induction of Ostβ and Cyp2b10 RNA was impaired in CA-fed and DDC-fed hs-RxrαΔex4(-/-) mice. Surprisingly, DDC-fed hs-RxrαΔex4(-/-) mice showed attenuated fibrosis compared to DDC-fed WT mice. These two models of cholestasis identify common and injury-specific roles for RXRα heterodimers and the functional relevance of an intact RXRα-DBD in the hepatocytic adaptive cholestatic response. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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Photoactive bile salts with critical micellar concentration in the micromolar range.
Gomez-Mendoza, Miguel; Marin, M Luisa; Miranda, Miguel A
2016-05-14
The aggregation behavior of bile salts is strongly dependent on the number of hydroxyl groups. Thus, cholic acid (CA), with three hydroxyls, starts forming aggregates at 15 mM, while deoxycholic, chenodeoxycholic or ursodeoxycholic acids, with two hydroxyls, start aggregating at 5-10 mM; for lithocholic acid, with only one hydroxyl group, aggregation is observed at lower concentration (2-3 mM). Here, the singular self-assembling properties of dansyl and naproxen derivatives of CA (3β-Dns-CA and 3β-NPX-CA, respectively) have been demonstrated on the basis of their photoactive properties. Thus, the emission spectra of 3β-Dns-CA registered at increasing concentrations (25-140 μM) showed a remarkable non-linear enhancement in the emission intensity accompanied by a hypsochromic shift of the maximum and up to a three-fold increase in the singlet lifetime. The inflection point at around 50-70 μM pointed to the formation of unprecedented assemblies at such low concentrations. In the case of 3β-NPX-CA, when the NPX relative triplet lifetime was plotted against concentration, a marked increase (up to two-fold) was observed at 40-70 μM, indicating the formation of new 3β-NPX-CA assemblies at ca. 50 μM. Additional evidence supporting the formation of new 3β-Dns-CA or 3β-NPX-CA assemblies at 40-70 μM was obtained from singlet excited state quenching experiments using iodide. Moreover, to address the potential formation of hybrid assemblies, 1 : 1 mixtures of 3β-Dns-CA and 3β-NPX-CA (2-60 μM, total concentration) were subjected to steady-state fluorescence experiments, and their behavior was compared to that of the pure photoactive derivatives. A lower increase in the emission was observed for 3β-NPX-CA in the mixture, while a huge increase was experienced by 3β-Dns-CA in the same concentration range (up to 60 μM total). A partial intermolecular energy transfer from NPX to Dns, consistent with their reported singlet energies, was revealed, pointing to the formation of extremely fluorescent hybrid assemblies at 5-10 μM (total concentration). The morphology of the entities was investigated by means of confocal microscopy. At 90 μM, 3β-Dns-CA showed disperse assemblies in the μm range.
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Nido, Sonia Agostinho; Shituleni, Shituleni Andreas; Mengistu, Berhe Mekonnen; Liu, Yunhuan; Khan, Alam Zeb; Gan, Fang; Kumbhar, Shahnawaz; Huang, Kehe
2016-06-01
A total of 80 female albino mice were randomly allotted into five groups (n = 16) as follows: (A) normal control, (B) high-fat diet (HFD),; (C) HFD + probiotics (P), (D) HFD + sodium selenite (SS), and (E) HFD + selenium-enriched probiotics (SP). The selenium content of diets in groups A, B, C, D, and E was 0.05, 0.05, 0.05, 0.3, and 0.3 μg/g, respectively. The amount of probiotics contained in groups C and E was similar (Lactobacillus acidophilus 0.25 × 10(11)/mL and Saccharomyces cerevisiae 0.25 × 10(9)/mL colony-forming units (CFU)). The high-fat diet was composed of 15 % lard, 1 % cholesterol, 0.3 % cholic acid, and 83.7 % basal diet. At the end of the 4-week experiment, blood and liver samples were collected for the measurements of lipid metabolism, antioxidative status, histopathological lesions, and related gene expressions. The result shows that HFD significantly increased the body weights and liver damages compared to control, while P, SS, or SP supplementation attenuated the body weights and liver damages in mice. P, SS, or SP supplementation also significantly reversed the changes of alanine aminotransferase (AST), aspartate aminotransferase (ALT), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), total protein (TP), high-density lipoprotein (HDL), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalasa (CAT), and malondialdehyde (MDA) levels induced by HFD. Generally, adding P, SS, or SP up-regulated mRNA expression of carnitine palmitoyltransferase-I (CPT1), carnitine palmitoyltransferase II (CPT2), acetyl-CoA acetyltransferase II (ACAT2), acyl-coenzyme A oxidase (ACOX2), and peroxisome proliferator-activated receptor alpha (PPARα) and down-regulated mRNA expression of fatty acid synthase (FAS), lipoprotein lipase (LPL), peroxisome proliferator-activated receptor gamma (PPARγ), and sterol regulatory element-binding protein-1 (SREBP1) involved in lipid metabolism. Among the group, adding SP has a maximum effect in improving lipid metabolism, antioxidative status, histopathological lesions, and related gene expression in mice fed a HFD.
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McGinn, B J; Morrison, J D
2016-06-28
Experiments have been undertaken to determine the extent to which cholic acid conjugates of insulin were absorbed from the small intestine of anaesthetised rats by means of the bile salt transporters of the ileum. The measure used to assess the absorption of the cholyl-insulins was the amount of hypoglycaemia following infusion into the small intestine. Control experiments involving infusion of natural insulin into the ileum showed either nil absorption or absorption of a small amount of insulin as indicated by transient dip in the blood glucose concentration. However, when insulin was co-infused with the bile salt taurocholate, this was followed by a marked hypoglycaemic response which was specific to the ileum and did not occur on infusion into the jejunum. When the two cholyl conjugates of insulin were tested viz. B(29)-Lys-cholyl-insulin and B(1)-Phe-cholyl-insulin, both were biologically active as indicated by hypoglycaemic responses on systemic injection, though their potency was about 40% of that of natural insulin. While there was no evidence for the absorption of B(29)-Lys-cholyl-insulin when infused into the ileum, B(1)-Phe-cholyl-insulin did cause a long lasting hypoglycaemic response, indicating that absorption had occurred. Since the hypoglycaemic response was blocked on co-infusion with taurocholate and was absent for infusion of the conjugate into the jejunum, these results were taken as evidence that B(1)-Phe-cholyl-insulin had been taken up by the ileal bile salt transporters. This would indicate that B(1)-Phe-cholyl-insulin is worthy of further investigation for use in an oral insulin formulation. Copyright © 2016. Published by Elsevier B.V.
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Santos-López, Jorge A; Garcimartín, Alba; Merino, Pinar; López-Oliva, M Elvira; Bastida, Sara; Benedí, Juana; Sánchez-Muniz, Francisco J
2016-01-01
Pork is an essential component of the diet that has been linked with major degenerative diseases and development of non-alcoholic steatohepatitis (NASH). Previous studies have. Previous studies have demonstrated the in vitro antioxidant activity of silicon (Si). Furthermore, when Si is added to restructured pork (RP) strongly counterbalances the negative effect of high-cholesterol-ingestion, acting as an active hypocholesterolemic and hypolipemic dietary ingredient in aged rats. This study was designed to evaluate the effects of Si vs hydroxytyrosol (HxT) RP on liver antioxidant defense in aged rats fed cholesterol-enriched high saturated/high cholesterol diets as a NASH model. Four diets were prepared: Control RP diet (C) with non-added cholesterol; Cholesterol-enriched high-saturated/high-cholesterol control RP diet (CHOL-C) with added cholesterol and cholic acid; Si- or HxT-RP cholesterol-enriched high-saturated/high-cholesterol diets (CHOL-Si and CHOL-HxT). Groups of six male Wistar rats (1-yr old) were fed these modified diets for eight weeks. Total cholesterol, hepatosomatic index, liver Nrf2 and antioxidant (CAT, SOD, GSH, GSSG, GR, GPx) markers were determined. Both CHOL-Si and CHOL-HxT diets enhanced the liver antioxidant status, reduced hepatosomatic index and increased SOD actvity. Hydrogen peroxide removal seemed to be involved, explaining that the value of redox index was even lower than C without changing the CAT activity. CHOL-Si results were quite better than CHOL-HxT in most measured parameters. Our study suggests that Si incorporated into RP matrix was able to counterbalance, more efficiently than HxT, the deleterious effect of consuming a high-saturated/high-cholesterol diet, by improving the liver antioxidant defenses in the context of NASH.
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Merino, Pinar; López-Oliva, M. Elvira; Bastida, Sara; Benedí, Juana; Sánchez-Muniz, Francisco J.
2016-01-01
Background Pork is an essential component of the diet that has been linked with major degenerative diseases and development of non-alcoholic steatohepatitis (NASH). Previous studies have. Previous studies have demonstrated the in vitro antioxidant activity of silicon (Si). Furthermore, when Si is added to restructured pork (RP) strongly counterbalances the negative effect of high-cholesterol-ingestion, acting as an active hypocholesterolemic and hypolipemic dietary ingredient in aged rats. Objective This study was designed to evaluate the effects of Si vs hydroxytyrosol (HxT) RP on liver antioxidant defense in aged rats fed cholesterol-enriched high saturated/high cholesterol diets as a NASH model. Methods Four diets were prepared: Control RP diet (C) with non-added cholesterol; Cholesterol-enriched high-saturated/high-cholesterol control RP diet (CHOL-C) with added cholesterol and cholic acid; Si- or HxT-RP cholesterol-enriched high-saturated/high-cholesterol diets (CHOL-Si and CHOL-HxT). Groups of six male Wistar rats (1-yr old) were fed these modified diets for eight weeks. Total cholesterol, hepatosomatic index, liver Nrf2 and antioxidant (CAT, SOD, GSH, GSSG, GR, GPx) markers were determined. Results Both CHOL-Si and CHOL-HxT diets enhanced the liver antioxidant status, reduced hepatosomatic index and increased SOD actvity. Hydrogen peroxide removal seemed to be involved, explaining that the value of redox index was even lower than C without changing the CAT activity. CHOL-Si results were quite better than CHOL-HxT in most measured parameters. Conclusions Our study suggests that Si incorporated into RP matrix was able to counterbalance, more efficiently than HxT, the deleterious effect of consuming a high-saturated/high-cholesterol diet, by improving the liver antioxidant defenses in the context of NASH. PMID:26807847
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The effect of simvastatin, aspirin, and their combination in reduction of atheroma plaque
NASA Astrophysics Data System (ADS)
Kurniati, Neng Fisheri; Permatasari, Anita
2015-09-01
Atherosclerosis is one of the risk factors of cardiovascular disease. Atherosclerosis is a chronic inflammatory disease caused by high level of cholesterol especially low density lipoprotein (LDL) and accumulation of neutrophil and macrophage in the artery wall. Thickness of aortic wall is an early stage of atherosclerosis plaque formation. Identification of atherosclerosis plaque formation was done by measuring level of total cholesterol, triglycerides, HDL, LDL, interleukin-18 (IL-18), myeloperoxidase (MPO) and measuring the thickness of aortic wall. Atherosclerosis's model induced by high fat diet and CCT (cholesterol, cholic acid, and propyltiouracil) oral administration. Rats induced cholesterol divided into positive control, simvastatin 25 mg/kg bw, aspirin 20 mg/kg bw, and combination simvastatin 25 mg/kg and aspirin 20 mg/kg bw group for 3 weeks. In the third week, therapy was given to atherosclerosis's model. Then, in the fourth and fifth week, therapy was given but induction of high cholesterol was stopped due to the massive loss of body weight. Total cholesterol, triglycerides, HDL, LDL, MPO, and IL-18 measured by uv-vis spectrophotometry and ELISA. In the end of therapy, aorta's rats was isolated to identify the thickness of aorta wall. In the fourth week, after 1 week of treatment, only combination group showed significantly higher total cholesterol, LDL and MPO compared to positive control group. Level of triglycerides and HDL in all groups did not significantly differ compared to positive control group. After 2 weeks continuing drug treatment, the level of total cholesterol, MPO, and IL-18 were decreased in all groups, and aspirin group showed the lowest level. The level of triglycerides was decreased in simvastatin and aspirin group, and aspirin group showed the lowest. Only combination group showed the lowest level of LDL. Based on histopathology result, the thickness of aortic wall was reduced in all groups and aspirin group showed the lowest.
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Effects of the duration of hyperlipidemia on cerebral lipids, vessels and neurons in rats.
Yang, Weichun; Shi, He; Zhang, Jianfen; Shen, Ziyi; Zhou, Guangyu; Hu, Minyu
2017-01-31
The present study was designed to investigate the effects of hyperlipidemia on the cerebral lipids, vessels and neurons of rats, and to provide experimental evidence for subsequent intervention. One hundred adult SD rats, half of which were male and half of which were female, were randomly divided into five groups on the basis of serum total cholesterol (TC) levels. Four groups were fed a hypercholesterolemic diet (rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5% thiouracil - this is also called a CCT diet) for periods of 1 week, 2 weeks, 3 weeks and 4 weeks, respectively. A control group was included. The levels of serum lipids, cerebral lipids, free fatty acids (FFA), interleukin-6 (IL-6), interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), oxidized low density lipoprotein (ox-LDL), A-beta precursor proteins (APP), amyloid beta (Aβ), glial fibrillary acidic protein (GFAP) and tight junction protein Claudin-5 were measured after the experiment. The pathologic changes and apoptosis of the rat brains were evaluated. Compared with the control group, after 1 week of a CCT diet, the levels of serum total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and brain triglycerides had increased by 2.40, 1.29 and 1.75 and 0.3 times, respectively. The serum high density lipoprotein cholesterol (HDL-C) had decreased by 0.74 times (P < 0.05) and the expression of IL-1, TNF-α and GFAP in the brains had increased (P < 0.05). In the second week, the expression of FFA and APP in the brains, and the amount of apoptotic neurons, had increased (P < 0.05). In the third week, the levels of VEGF, Ox-LDL and Aβ had increased, and the expression of Claudin-5 had decreased in the brains (P < 0.05). In the fourth week, the levels of TC, LDL-C and the amount of apoptotic neurons had increased (P < 0.05). The correlation analysis showed a positive correlation among FFA, TNF-α, VEGF, ox-LDL, Aβ, GFAP and neuronal apoptosis in the rat brains, and they all were negatively correlated with Claudin-5 (P < 0.05). Hyperlipidemia may activate astrocytes by means of high levels of TG that will have direct toxic effects on the cerebral vessels and neurons by causing the secretion of TNF-α and IL-1 in the brains of rats. In the metabolic procession, brain tissue was shown to generate FFA that aggravated the biosynthesis of ox-LDL. With the extension of the duration of hyperlipidemia, high levels of cerebral TC and LDL-C were shown to aggravate the deposition of Aβ, induce the secretion of VEGF, reduce the expression of tight junction protein Claudin-5 and change the permeability of blood-brain barriers to factors that could damage cerebral vessels and neurons.
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Functional characterization of 3-ketosteroid 9α-hydroxylases in Rhodococcus ruber strain chol-4.
Guevara, Govinda; Heras, Laura Fernández de Las; Perera, Julián; Llorens, Juana María Navarro
2017-09-01
The 3-Ketosteroid-9α-Hydroxylase, also known as KshAB [androsta-1,4-diene-3,17-dione, NADH:oxygen oxidoreductase (9α-hydroxylating); EC 1.14.13.142)], is a key enzyme in the general scheme of the bacterial steroid catabolism in combination with a 3-ketosteroid-Δ 1 -dehydrogenase activity (KstD), being both responsible of the steroid nucleus (rings A/B) breakage. KshAB initiates the opening of the steroid ring by the 9α-hydroxylation of the C9 carbon of 4-ene-3-oxosteroids (e.g. AD) or 1,4-diene-3-oxosteroids (e.g. ADD), transforming them into 9α-hydroxy-4-androsten-3,17-dione (9OHAD) or 9α-hydroxy-1,4-androstadiene-3,17-dione (9OHADD), respectively. The redundancy of these enzymes in the actinobacterial genomes results in a serious difficulty for metabolic engineering this catabolic pathway to obtain intermediates of industrial interest. In this work, we have identified three homologous kshA genes and one kshB gen in different genomic regions of R. ruber strain Chol-4. We present a set of data that helps to understand their specific roles in this strain, including: i) description of the KshAB enzymes ii) construction and characterization of ΔkshB and single, double and triple ΔkshA mutants in R. ruber iii) growth studies of the above strains on different substrates and iv) genetic complementation and biotransformation assays with those strains. Our results show that KshA2 isoform is needed for the degradation of steroid substrates with short side chain, while KshA3 works on those molecules with longer side chains. KshA1 is a more versatile enzyme related to the cholic acid catabolism, although it also collaborates with KshA2 or KshA3 activities in the catabolism of steroids. Accordingly to what it is described for other Rhodococcus strains, our results also suggest that the side chain degradation is KshAB-independent. Copyright © 2017 Elsevier Ltd. All rights reserved.
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NASA Astrophysics Data System (ADS)
Al Awwad, Nasir
Nanotechnology is the arrangement of materials, and devices which permit technology to operate in nanometer-sized objects. Some of the potential applications of these nanomaterials include light harvesting for solar cells, light emitting enhancer for LEDs, cosmetics, and nanocarriers for pesticide applications and drug delivery. The impact of nanomaterials on the environment is a concern. The Lam laboratory has developed a novel nanocarrier system for the delivery of hydrophobic drugs or imaging agents against tumors. This nanocarriers are based on polyethylene glycol-cholic acid cluster telodendrimers which can self-assemble to form micellar structure. Here we report on the ability of these nanocarriers to cross the blood brain barrier (BBB) in murine model, and the GI absorption of the nanocarrier in Caenorhabditis elegans models. In addition, we also studied the uptake of the nanocarriers by Arabidopsis Thaliana seedlings and Nicotina bethamiana leaves, Application of three different biological organisms were used, one mammalian, one invertebrate, and one plant. Drug delivery to the central nervous system is not easy as compared to other body organs due to the presence of the BBB. It is essential that any delivery system to the central nervous system (CNS) needs to be efficient and non-toxic. Adenosine receptor agonists have been reported to be able to modulate the permeability of the BBB to macromolecules. Here, we studied the effect of 5'-(NEthylcarboxamido) (NECA), an adenosine receptor agonist, on the penetration of both non-crosslinked micelle (NCM) and disulfide cross-linked micelle (DCM) through the blood brain barrier into the brain parenchyma. We found that NECA given at 5.3 mg/kg intravenously, was able to facilitate the delivery of fluorescentlabeled NCM, DCM and polyvinyl alcohol (PVA) based nanocarriers to organs or blood vessels expressing adenosine receptors, which also include the brain. After ingestion, both DCM and NCM were localized inside the gastrointestinal tract of the C. elegans for about 4 days. Neither DCM nor NCM could pass through plants cell walls, but they accumulate into the vascular system of the plant.
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Venkatesan, Nandini; Devaraj, S Niranjali; Devaraj, H
2007-01-01
LDL (low-density lipoprotein) oxidation is a key trigger factor for the development of atherosclerosis. Relatively few studies exist on the impact of dietary fibre on LDL oxidation. This study was undertaken to evaluate the influence of a novel fibre mix of fenugreek seed powder, guar gum and wheat bran (Fibernat) on LDL oxidation induced by an atherogenic diet. Male Wistar albino rats were administered one of the following diets: (1) a control diet that was fibre-free (Group I); (2) an atherogenic diet containing 1.5% cholesterol and 0.1% cholic acid (Group II) or (3) an atherogenic diet supplemented with Fibernat (Group III). Peroxidative changes in low-density lipoprotein (LDL) and the oxidative susceptibility of LDL and the LDL + VLDL (very low-density lipoprotein) fraction were determined. As a corollary to the oxidative modification theory, the titer of autoantibodies to oxidised LDL (oxLDL) was determined at various time points of the study. In addition, plasma homocysteine (tHcy) and lipoprotein (Lp (a)), apolipoprotein (apoB), cholesterol, triglyceride, phospholipid and alpha-tocopherol content of LDL were determined. A decrease in malonaldehyde (MDA) content (p<0.05) and relative electrophoretic mobility (REM) of LDL was observed in the group III rats as compared to the group II rats. An increase in lag time to oxidation (p<0.01) and decrease in maximum oxidation (p<0.01) and oxidation rate (p<0.01) were observed in the LDL + VLDL fraction of group III rats. In group II rats, formation of autoantibodies to oxLDL occurred at an earlier time point and at levels greater than in the group III rats. Fibernat, had a sparing effect on LDL alpha-tocopherol, which was about 51% higher in the group III rats than in the group II rats; apo B content of LDL was reduced by 37.6% in group III rats. LDL of group III rats displayed a decrease in free and ester cholesterol (p<0.01) as compared to that of group II. A decrease in plasma homocysteine (p<0.01) and an increase in GSH (p<0.05) were also observed in group III rats when compared with that of group II. Fibernat administration appears to combat oxidative stress resulting in a trend to lower oxidative modification of LDL. In addition, the cholesterol and apo B content of LDL were reduced significantly with a sparing effect on LDL alpha-tocopherol. This novel fibre preparation could be an effective diet therapy and therefore needs further investigation.
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Dumas, Laurent S; Briand, François; Clerc, Romain; Brousseau, Emmanuel; Montemagno, Christopher; Ahmadi, Mitra; Bacot, Sandrine; Soubies, Audrey; Perret, Pascale; Riou, Laurent M; Devoogdt, Nick; Lahoutte, Tony; Barone-Rochette, Gilles; Fagret, Daniel; Ghezzi, Catherine; Sulpice, Thierry; Broisat, Alexis
2017-07-01
The addition of ezetimibe, an intestinal cholesterol absorption inhibitor, to statin therapy has recently shown clinical benefits in the Improved Reduction of Outcomes: Vytorin Efficacy International Trial by reducing low-density-lipoprotein (LDL) cholesterol levels more than statin therapy alone. Here, we investigated the mechanisms by which inhibition of intestinal cholesterol absorption might contribute to the clinically observed reduction in cardiovascular events by evaluating its effect on inflammatory plaque development in apolipoprotein E -/- mice. Methods: Apolipoprotein E -/- mice were fed the Paigen diet (1.25% cholesterol, 0.5% cholic acid, and 15% fat) without or with ezetimibe (7 mg/kg/d) for 6 wk. In a first set of mice ( n = 15), we intravenously injected 3 H-cholesteryl oleate-labeled human LDL to test whether ezetimibe promotes LDL-derived cholesterol fecal excretion. In a second set ( n = 20), we used the imaging agent 99m Tc-cAbVCAM1-5 to evaluate expression of an inflammatory marker, vascular cell adhesion molecule 1 (VCAM-1), in atherosclerotic plaques. In a third set ( n = 21), we compared VCAM-1 expression with 99m Tc-cAbVCAM1-5 uptake in various tissues. Results: Mice treated with ezetimibe showed a 173% higher LDL-cholesteryl ester plasma disappearance rate ( P < 0.001 vs. control) after 3 H-cholesteryl oleate-labeled LDL injection. At 96 h after injection, the hepatic fraction of 3 H-tracer was 61% lower in mice treated with ezetimibe ( P < 0.001). Meanwhile, LDL-derived 3 H-cholesterol excretion in the feces was 107% higher ( P < 0.001). The antiatherogenic effect of ezetimibe monitored by 99m Tc-cAbVCAM1-5 SPECT showed a 49% reduction in aortic tracer uptake (percentage injected dose per cubic centimeter, 0.95 ± 0.04 vs. 1.87 ± 0.11; P < 0.01). In addition to hypercholesterolemia, the proinflammatory Paigen diet significantly increased VCAM-1 expression with respect to the control group in various tissues, including the aorta, and this expression correlated strongly with 99m Tc-cAbVCAM1-5 uptake ( r = 0.75; P < 0.05). Conclusion: Inhibition of intestinal cholesterol absorption with ezetimibe promotes antiatherosclerotic effects through increased LDL cholesterol catabolism and LDL-derived cholesterol fecal excretion and reduces inflamed atherosclerotic plaques. These mechanisms may contribute to the benefits of adding ezetimibe to a statin therapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.
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Yang, Weichun; Shen, Ziyi; Wen, Sixian; Wang, Wei; Hu, Minyu
2018-02-07
Lycopene is a kind of carotenoid, with a strong capacity of antioxidation and regulating the bloodlipid. There has been some evidence that lycopene has protective effects on the central nervous system, but few studies have rigorously explored the role of neurotransmitters in it. Therefore, the present study was designed to investigate the effects of several neurotransmitters as lycopene exerts anti-injury effects induced by hyperlipidemia. Eighty adult SD rats, half male and half female, were randomly divided into eight groups on the basis of serum total cholesterol (TC) levels and body weight. There was a control group containing rats fed a standard laboratory rodent chow diet (CD); a hypercholesterolemic diet (rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5% thiouracil - this is also called a CCT diet) group; a positive group (CCT + F) fed CCT, supplemented with 10 mg·kg·bw - 1 ·d - 1 fluvastatin sodium by gastric perfusion; and lycopene groups at five dose levels (CCT + LYCO) fed with CCT and supplied lycopene at doses of 5, 25, 45, 65, and 85 mg·kg·bw - 1 ·d - 1 . The levels of TC, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-α), oxidized low density lipoprotein (ox-LDL), low-density lipoprotein receptor (LDLR), nerve growth factor (NGF), glutamic acid (Glu), Gamma aminobutyric acid (GABA), dopamine (DA), 5-hydroxytryptamine (5-HT), N-methyl-D-aspartate (NMDA1R), GABA A , 5-HT 1 , D 1 , and apoptosis-related proteins Caspase3, bax, and bcl-2 were measured after the experiment. Nissl staining was adopted to observe the morphological changes in neurons. At the end of the experiment, the levels of TC, TG, LDL-C, IL-1, TNF-α, and ox-LDL in the serum and brain as well as the content of Glu, DA, NMDA, and D 1 in the brain of rats in the CCT group were higher than those in the control group (P<0.05); the levels of LDLR, NGF, GABA, 5-HT, GABA A , 5-HT 1 , and neuron quantities in the hippocampal CA1 and CA3 areas were lower than those in the control group (P<0.05). Compared to the CCT group, levels of TC, TG, LDL-C, IL-1, TNF-α, and ox-LDL in the serum and brain, as well as the content of Glu, DA and the expression of pro-apoptotic Caspase3 in the brain decreased in the rats with lycopene (25 mg to 85 mg) added to the diet (P<0.05); the levels of LDLR, NGF, GABA, 5-HT, GABA A , and 5-HT 1 as well as the expression of anti-apoptotic bcl-2 and the neuron quantity in hippocampal CA1 and CA3 areas increased (P<0.05); further, the hippocampal cells were closely arranged. Lycopene dose was negatively correlated with the levels of TC, TG, and LDL-C in the serum and brain as well as levels of IL-1, TNF-α, ox-LDL, Glu/GABA, NMDA1R, and Caspase3 (P<0.05); it was positively correlated with the levels of LDLR, NGF, 5-HT, 5-HT 1 , GABA A , bcl-2, and the neuron quantity in hippocampal CA1 and CA3 areas (P<0.05). Lycopene exerts anti-injury effects in the brain as-induced by hyperlipidemia. It can inhibit the elevation of serum TC, TG, and LDL-C in rats with hyperlipidemia while indirectly affecting the levels of TC, TG, and LDL-C in the brain, leading to a reduction in ox-LDL, IL-1, and TNF-α in the brain. This inhibits the release of Glu, which weakens nerve toxicity and downregulates pro-apoptotic Caspase3. Lycopene also plays an anti-injury role by promoting the release of the inhibitory neurotransmitter GABA and 5-HT, which enhances the protective effect, and by upregulating the anti-apoptotic bcl-2.
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NASA Astrophysics Data System (ADS)
Krimmel, Birgit; Swoboda, Friederike; Solar, Sonja; Reznicek, Gottfried
2010-12-01
The OH-radical induced degradation of hydroxybenzoic acids (HBA), hydroxycinnamic acids (HCiA) and methoxylated derivatives, as well as of chlorogenic acid and rosmarinic acid was studied by gamma radiolysis in aerated aqueous solutions. Primary aromatic products resulting from an OH-radical attachment to the ring (hydroxylation), to the position occupied by the methoxyl group (replacement -OCH 3 by -OH) as well as to the propenoic acid side chain of the cinnamic acids (benzaldehyde formations) were analysed by HPLC-UV and LC-ESI-MS. A comparison of the extent of these processes is given for 3,4-dihydroxybenzoic acid, vanillic acid, isovanillic acid, syringic acid, cinnamic acid, 4-hydroxycinnamic acid, caffeic acid, ferulic acid, isoferulic acid, chlorogenic acid, and rosmarinic acid. For all cinnamic acids and derivatives benzaldehydes were significant oxidation products. With the release of caffeic acid from chlorogenic acid the cleavage of a phenolic glycoside could be demonstrated. Reaction mechanisms are discussed.
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Arimboor, Ranjith; Kumar, K Sarin; Arumughan, C
2008-05-12
A RP-HPLC-DAD method was developed and validated for the simultaneous analysis of nine phenolic acids including gallic acid, protocatechuic acid, p-hydroxybenzoic acid, vanillic acid, salicylic acid, p-coumaric acid, cinnamic acid, caffiec acid and ferulic acid in sea buckthorn (SB) (Hippophaë rhamnoides) berries and leaves. The method was validated in terms of linearity, LOD, precision, accuracy and recovery and found to be satisfactory. Phenolic acid derivatives in anatomical parts of SB berries and leaves were separated into free phenolic acids, phenolic acids bound as esters and phenolic acids bound as glycosides and profiled in HPLC. Berry pulp contained a total of 1068 mg/kg phenolic acids, of which 58.8% was derived from phenolic glycosides. Free phenolic acids and phenolic acid esters constituted 20.0% and 21.2%, respectively, of total phenolic acids in SB berry pulp. The total phenolic acid content in seed kernel (5741 mg/kg) was higher than that in berry pulp and seed coat (Table 2). Phenolic acids liberated from soluble esters constituted the major fraction of phenolic acids (57.3% of total phenolic acids) in seed kernel. 8.4% and 34.3% of total phenolic acids in seed kernel were, respectively contributed by free and phenolic acids liberated from glycosidic bonds. The total soluble phenolic acids content in seed coat (448 mg/kg) was lower than that in seed kernel and pulp (Table 2). Proportion of free phenolic acids in total phenolic acids in seed coat was higher than that in seed kernel and pulp. Phenolic acids bound as esters and glycosides, respectively contributed 49.1% and 20.3% of total phenolic acids in seed coat. The major fraction (approximately 70%) of phenolic acids in SB berries was found to be concentrated in the seeds. Gallic acid was the predominant phenolic acid both in free and bound forms in SB berry parts and leaves.
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Kanoh, H.; Lindsay, D. B.
1972-01-01
1. Mitochondrial and microsomal fractions of rat epididymal adipose tissue incorporated [1-14C]acetyl-CoA equally well into various fatty acids by a chain-elongation mechanism. C18 and C20 fatty acids were the two major products, and comprised about 80% of the total fatty acids synthesized in both particles. 2. When incubated in air, mitochondria synthesized stearic acid, octadecenoic acid and eicosamonoenoic acid in almost equal amounts (about 20% each), whereas in microsomal fractions, the synthesis of octadecenoic acid was more than fivefold the stearic acid formation. In both fractions, major components of synthesized monoenoic fatty acids were the Δ11:12 isomers. Hexadecenoic acid and octadecenoic acid from whole adipose tissue contained approx. 11 and 14% of the Δ11:12 isomer respectively. 3. When mitochondria or microsomal fractions were incubated in nitrogen, there was increased synthesis of stearic acid and palmitic acid and less of C16 and C18 monoenoic acids; synthesis of C20 acids remained predominantly of the monoenoic acids. Determination of the position of the double bond in the monoenoic acids supported the view that the synthesis of hexadecenoic acid and octadecenoic acid involves a desaturase activity, whereas eicosamonoenoic acid and eicosadienoic acid are formed only by elongation of endogenous fatty acids. 4. Most of the radioactivity was found in free fatty acids (63%) and the phospholipid (26%) fraction. In phospholipids, phosphatidylcholine and phosphatidylethanolamine were the two major components. 5. Most of the fatty acids synthesized, including those not normally found in particle lipids (arachidic acid, eicosamonoenoic acid and eicosadienoic acid) were distributed fairly evenly in the phospholipid and free fatty acid fractions. However, stearic acid was found predominantly in the phospholipid fraction. PMID:4638795
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Gao, Chao; Qiu, Jianhua; Li, Jingchen; Ma, Cuiqing; Tang, Hongzhi; Xu, Ping
2009-03-01
D-lactic acid and pyruvic acid are two important building block intermediates. Production of D-lactic acid and pyruvic acid from racemic lactic acid by biotransformation is economically interesting. Biocatalyst prepared from 9 g dry cell wt l(-1) of Pseudomonas stutzeri SDM could catalyze 45.00 g l(-1)DL-lactic acid into 25.23 g l(-1)D-lactic acid and 19.70 g l(-1) pyruvic acid in 10h. Using a simple ion exchange process, D-lactic acid and pyruvic acid were effectively separated from the biotransformation system. Co-production of d-lactic acid and pyruvic acid by enantioselective oxidation of racemic lactic acid is technically feasible.
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DeFilippis, Andrew P; Harper, Charles R; Cotsonis, George A; Jacobson, Terry A
2009-01-01
We previously reported a >50% increase in mean plasma eicosapentaenoic acid levels in a general medicine clinic population after supplementation with alpha-linolenic acid. In the current analysis, we evaluate the variability of changes in eicosapentaenoic acid levels among individuals supplemented with alpha-linolenic acid and evaluated the impact of baseline plasma fatty acids levels on changes in eicosapentaenoic acid levels in these individuals. Changes in eicosapentaenoic acid levels among individuals supplemented with alpha-linolenic acid ranged from a 55% decrease to a 967% increase. Baseline plasma fatty acids had no statistically significant effect on changes in eicosapentaenoic levels acid after alpha-linolenic acid supplementation. Changes in eicosapentaenoic acid levels varied considerably in a general internal medicine clinic population supplemented with alpha-linolenic acid. Factors that may impact changes in plasma eicosapentaenoic acid levels after alpha-linolenic acid supplementation warrant further study.
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Barrett, Eoin; Fitzgerald, Patrick; Dinan, Timothy G; Cryan, John F; Ross, R Paul; Quigley, Eamonn M; Shanahan, Fergus; Kiely, Barry; Fitzgerald, Gerald F; O'Toole, Paul W; Stanton, Catherine
2012-01-01
The aim of this study was to compare the impact of dietary supplementation with a Bifidobacterium breve strain together with linoleic acid & α-linolenic acid, for 7 weeks, on colonic sensitivity and fatty acid metabolism in rats. Maternally separated and non-maternally separated Sprague Dawley rats (n = 15) were orally gavaged with either B. breve DPC6330 (10(9) microorganisms/day) alone or in combination with 0.5% (w/w) linoleic acid & 0.5% (w/w) α-linolenic acid, daily for 7 weeks and compared with trehalose and bovine serum albumin. Tissue fatty acid composition was assessed by gas-liquid chromatography and visceral hypersensitivity was assessed by colorectal distension. Significant differences in the fatty acid profiles of the non-separated controls and maternally separated controls were observed for α-linolenic acid and arachidonic acid in the liver, oleic acid and eicosenoic acid (c11) in adipose tissue, and for palmitoleic acid and docosahexaenoic acid in serum (p<0.05). Administration of B. breve DPC6330 to MS rats significantly increased palmitoleic acid, arachidonic acid and docosahexaenoic acid in the liver, eicosenoic acid (c11) in adipose tissue and palmitoleic acid in the prefrontal cortex (p<0.05), whereas feeding B. breve DPC6330 to non separated rats significantly increased eicosapentaenoic acid and docosapentaenoic acid in serum (p<0.05) compared with the NS un-supplemented controls. Administration of B. breve DPC6330 in combination with linoleic acid and α-linolenic acid to maternally separated rats significantly increased docosapentaenoic acid in the serum (p<0.01) and α-linolenic acid in adipose tissue (p<0.001), whereas feeding B. breve DPC6330 with fatty acid supplementation to non-separated rats significantly increased liver and serum docosapentaenoic acid (p<0.05), and α-linolenic acid in adipose tissue (p<0.001). B. breve DPC6330 influenced host fatty acid metabolism. Administration of B. breve DPC6330 to maternally separated rats significantly modified the palmitoleic acid, arachidonic acid and docosahexaenoic acid contents in tissues. The effect was not observed in non-separated animals.
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Barrett, Eoin; Fitzgerald, Patrick; Dinan, Timothy G.; Cryan, John F.; Ross, R. Paul; Quigley, Eamonn M.; Shanahan, Fergus; Kiely, Barry; Fitzgerald, Gerald F.; O'Toole, Paul W.; Stanton, Catherine
2012-01-01
The aim of this study was to compare the impact of dietary supplementation with a Bifidobacterium breve strain together with linoleic acid & α-linolenic acid, for 7 weeks, on colonic sensitivity and fatty acid metabolism in rats. Maternally separated and non-maternally separated Sprague Dawley rats (n = 15) were orally gavaged with either B. breve DPC6330 (109 microorganisms/day) alone or in combination with 0.5% (w/w) linoleic acid & 0.5% (w/w) α-linolenic acid, daily for 7 weeks and compared with trehalose and bovine serum albumin. Tissue fatty acid composition was assessed by gas-liquid chromatography and visceral hypersensitivity was assessed by colorectal distension. Significant differences in the fatty acid profiles of the non-separated controls and maternally separated controls were observed for α-linolenic acid and arachidonic acid in the liver, oleic acid and eicosenoic acid (c11) in adipose tissue, and for palmitoleic acid and docosahexaenoic acid in serum (p<0.05). Administration of B. breve DPC6330 to MS rats significantly increased palmitoleic acid, arachidonic acid and docosahexaenoic acid in the liver, eicosenoic acid (c11) in adipose tissue and palmitoleic acid in the prefrontal cortex (p<0.05), whereas feeding B. breve DPC6330 to non separated rats significantly increased eicosapentaenoic acid and docosapentaenoic acid in serum (p<0.05) compared with the NS un-supplemented controls. Administration of B. breve DPC6330 in combination with linoleic acid and α-linolenic acid to maternally separated rats significantly increased docosapentaenoic acid in the serum (p<0.01) and α-linolenic acid in adipose tissue (p<0.001), whereas feeding B. breve DPC6330 with fatty acid supplementation to non-separated rats significantly increased liver and serum docosapentaenoic acid (p<0.05), and α-linolenic acid in adipose tissue (p<0.001). B. breve DPC6330 influenced host fatty acid metabolism. Administration of B. breve DPC6330 to maternally separated rats significantly modified the palmitoleic acid, arachidonic acid and docosahexaenoic acid contents in tissues. The effect was not observed in non-separated animals. PMID:23185248
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Solid-phase extraction of acidic herbicides.
Wells, M J; Yu, L Z
2000-07-14
A discussion of solid-phase extraction method development for acidic herbicides is presented that reviews sample matrix modification, extraction sorbent selection, derivatization procedures for gas chromatographic analysis, and clean-up procedures for high-performance liquid chromatographic analysis. Acidic herbicides are families of compounds that include derivatives of phenol (dinoseb, dinoterb and pentachlorophenol), benzoic acid (acifluorfen, chloramben, dicamba, 3,5-dichlorobenzoic acid and dacthal--a dibenzoic acid derivative), acetic acid [2,4-dichlorophenoxyacetic acid (2,4-D), 4-chloro-2-methylphenoxyacetic acid (MCPA) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)], propanoic acid [dichlorprop, fluazifop, haloxyfop, 2-(4-chloro-2-methylphenoxy)propanoic acid (MCPP) and silvex], butanoic acid [4-(2,4-dichlorophenoxy)butanoic acid (2,4-DB) and 4-(4-chloro-2-methylphenoxy)butanoic acid (MCPB)], and other miscellaneous acids such as pyridinecarboxylic acid (picloram) and thiadiazine dioxide (bentazon).
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Boric acid and boronic acids inhibition of pigeonpea urease.
Reddy, K Ravi Charan; Kayastha, Arvind M
2006-08-01
Urease from the seeds of pigeonpea was competitively inhibited by boric acid, butylboronic acid, phenylboronic acid, and 4-bromophenylboronic acid; 4-bromophenylboronic acid being the strongest inhibitor, followed by boric acid > butylboronic acid > phenylboronic acid, respectively. Urease inhibition by boric acid is maximal at acidic pH (5.0) and minimal at alkaline pH (10.0), i.e., the trigonal planar B(OH)3 form is a more effective inhibitor than the tetrahedral B(OH)4 -anionic form. Similarly, the anionic form of phenylboronic acid was least inhibiting in nature.
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21 CFR 357.210 - Cholecystokinetic active ingredients.
Code of Federal Regulations, 2010 CFR
2010-04-01
... a melting point of 41 to 43.5 °C, an iodine value of 65 to 69, and a fatty acid composition as follows: Fatty acid Percent composition Myristic acid 0.1 Palmitic acid 10.0 Palmitoleic acid 0.1 Stearic acid 13.5 Oleic acid 72.0 Linoleic acid 3.8 Linolenic acid 0.1 Arachidic acid 0.5 Behenic acid 0.2 [54...
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21 CFR 357.210 - Cholecystokinetic active ingredients.
Code of Federal Regulations, 2011 CFR
2011-04-01
... a melting point of 41 to 43.5 °C, an iodine value of 65 to 69, and a fatty acid composition as follows: Fatty acid Percent composition Myristic acid 0.1 Palmitic acid 10.0 Palmitoleic acid 0.1 Stearic acid 13.5 Oleic acid 72.0 Linoleic acid 3.8 Linolenic acid 0.1 Arachidic acid 0.5 Behenic acid 0.2 [54...
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Liu, Zhipeng; Liu, Rui; Chou, Jing; Yu, Jiaying; Liu, Xiaowei; Sun, Changhao; Li, Ying; Liu, Liyan
2018-07-15
Maternal diet during pregnancy can influence offspring's health by affecting development and metabolism. This study aimed to analyze the influence of maternal folic acid (FA) supplementation on the metabolism of rat pups using targeted metabolomics. Twenty female rats were randomly assigned to a FA supplementation (FAS group, n = 10) or control group (n = 10), which were fed AIN93G diet with 2 or 10 mg/kg FA, respectively. We then measured amino acids and their derivatives, biogenic amines, and fatty acids in the female rats and their pups by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC/MS-MS) and gas chromatography-mass spectrometry (GC/MS-MS). In maternal rats, the significant changes of three metabolites (proline, γ-aminobutyric acid and esterified octadecatetraenoic acid, P < 0.05) were observed in FAS group. For the rat pups, FAS pups had significantly lower homocysteine and higher FA levels than control pups. The lower levels of amino acids (leucine, isoleucine, serine, proline) were obtained in FAS pups. Furthermore, there were the decreased esterified fatty acids (arachidonic acid, eicosapentaenoic acid, and docosatetraenoic acid) and free fatty acids (oleic acid, linoleic acid, γ-linolenic acid, octadecatetraenoic acid, arachidonic acid, eicosapentaenoic acid and selacholeic acid) in FAS pups. Metabolic changes in the FAS pups were characterized by changes in fatty acids and amino acids. These results suggested that FA supplementation during pregnancy influenced amino acids and fatty acids metabolism in rat pups. This study provides new insights into the regulation of amino acids and fatty acids metabolism during early life. Copyright © 2018 Elsevier B.V. All rights reserved.
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Clifford, Michael N; Stoupi, Stavroula; Kuhnert, Nikolai
2007-04-18
Green tea, tara tannin, and tannic acid have been profiled for their contents of galloylquinic acids using LC-MS8. These procedures have provided evidence for the first observation of (i) 1-galloylquinic acid (11), 1,3,5-trigalloylquinic acid (22), 4-(digalloyl)quinic acid (28), 5-(digalloyl)quinic acid (29), and either 3-galloyl-5-(digalloyl)quinic acid (32) or 3-(digalloyl)-5-galloylquinic acid (33) from any source; (ii) 4-galloyl-5-(digalloyl)quinic acid (34), 5-galloyl-4-(digalloyl)quinic acid (35), 3-(digalloyl)-4,5-digalloylquinic acid (41), 4-(digalloyl)-3,5-digalloylquinic acid (40), 5-(digalloyl)-3,4-digalloylquinic acid (39), and 1,3,4-trigalloylquinic acid (21) from tara tannin; and (iii) 3-galloylquinic acid (12) and 4-galloylquinic acid (14) from green tea. The first mass spectrometric fragmentation data are reported for galloylquinic acids containing between five and eight gallic acid residues. For each of these mass ranges at least two isomers based on the 1,3,4,5-tetragalloylquinic acid core (25) and at least three based on the 3,4,5-trigalloylquinic acid core (24) were observed. Methanolysis of tara tannin yielded methyl gallate, methyl digallate, and methyl trigallate, demonstrating that some of these galloylquinic acids contained at least one side chain of up to four galloyl residues.
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Mandal, Santi M; Chakraborty, Dipjyoti; Dutta, Suhrid R; Ghosh, Ananta K; Pati, Bikas R; Korpole, Suresh; Paul, Debarati
2016-06-01
A range of phenolic acids, viz., p-coumaric acid, 4-hydroxybenzaldehyde, 4-hydroxybenzoic acid, protocatechuic acid, caffeic acid, ferulic acid, and cinnamic acid have been isolated and identified by LC-MS analysis in the roots and root nodules of Mimosa pudica. The effects of identified phenolic acids on the regulation of nodulation (nod) genes have been evaluated in a betarhizobium isolate of M. pudica root nodule. Protocatechuic acid and p-hydroxybenzoic acid were most effective in inducing nod gene, whereas caffeic acid had no significant effect. Phenylalanine ammonia lyase, peroxidase, and polyphenol oxidase activities were estimated, indicating regulation and metabolism of phenolic acids in root nodules. These results showed that nodD gene expression of betarhizobium is regulated by simple phenolic acids such as protocatechuic acid and p-hydroxybenzoic acid present in host root nodule and sustains nodule organogenesis.
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Leenheer, J.A.; Wershaw, R. L.; Reddy, M.M.
1995-01-01
An investigation of the strong-acid characteristics (pKa 3.0 or less) of fulvic acid from the Suwannee River, Georgia, was conducted. Quantitative determinations were made for amino acid and sulfur-containing acid structures, oxalate half-ester structures, malonic acid structures, keto acid structures, and aromatic carboxyl-group structures. These determinations were made by using a variety of spectrometric (13C-nuclear magnetic resonance, infrared, and ultraviolet spectrometry) and titrimetric characterizations on fulvic acid or fulvic acid samples that were chemically derivatized to indicate certain functional groups. Only keto acid and aromatic carboxyl-group structures contributed significantly to the strong-acid characteristics of the fulvic acid; these structures accounted for 43% of the strong-acid acidity. The remaining 57% of the strong acids are aliphatic carboxyl groups in unusual and/or complex configurations for which limited model compound data are available.
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Fatty acids bound to recombinant tear lipocalin and their role in structural stabilization.
Tsukamoto, Seiichi; Fujiwara, Kazuo; Ikeguchi, Masamichi
2009-09-01
A variant of human tear lipocalin was expressed in Escherichia coli, and the bound fatty acids were analysed by gas chromatography, mass spectroscopy and nuclear magnetic resonance spectroscopy. Five major fatty acids were identified as hexadecanoic acid (palmitic acid, PA), cis-9-hexadecenoic acid (palmitoleic acid), 9,10-methylenehexadecanoic acid, cis-11-octadecenoic acid (vaccenic acid) and 11,12-methyleneoctadecanoic acid (lactobacillic acid). The composition of the bound fatty acids was similar to the fatty acid composition of E. coli extract, suggesting that the binding affinities are similar for these fatty acids. The urea-induced and thermal-unfolding transitions of the holoprotein (nondelipidated), apoprotein (delipidated) and PA-bound protein were observed by circular dichroism. Holoproteins and PA-bound proteins showed the same stability against urea and heat, and were more stable than apoprotein. These results show that each bound fatty acid stabilizes recombinant tear lipocalin to a similar extent.
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Carballeira, N M; Sostre, A; Stefanov, K; Popov, S; Kujumgiev, A; Dimitrova-Konaklieva, S; Tosteson, C G; Tosteson, T R
1997-12-01
The fatty acid composition of a new strain of Vibrio alginolyticus, found in the alga Cladophora coelothrix, was studied. Among 38 different fatty acids, a new fatty acid, 9-methyl-10-hexadecenoic acid and the unusual 11-methyl-12-octadecenoic acid, were identified. Linear alkylbenzene fatty acids, such as 10-phenyldecanoic acid, 12-phenyldodecanoic acid and 14-phenyltetradecanoic acid, were also found in V. alginolyticus. The alga contained 43% saturated fatty acids, and 28% C16-C20 polyunsaturated fatty acids of the n-3 and n-6 families.
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Du, M; Ahn, D U; Sell, J L
2000-12-01
A study was conducted to determine the effects of dietary conjugated linoleic acid (CLA) and the ratio of linoleic:linolenic acid on long-chain polyunsaturated fatty acid status. Thirty-two 31-wk-old White Leghorn hens were randomly assigned to four diets containing 8.2% soy oil, 4.1% soy oil + 2.5% CLA (4.1% CLA source), 4.1% flax oil + 2.5% CLA, or 4.1% soy oil + 4.1% flax oil. Hens were fed the diets for 3 wk before eggs and tissues were collected for the study. Lipids were extracted from egg yolk and tissues, classes of egg yolk lipids were separated, and fatty acid concentrations of total lipids, triglyceride, phosphatidylethanolamine, and phosphatidylcholine were analyzed by gas chromatography. The concentrations of monounsaturated fatty acids and non-CLA polyunsaturated fatty acids were reduced after CLA feeding. The amount of arachidonic acid was decreased after CLA feeding in linoleic acid- and linolenic acid-rich diets, but amounts of eicosapentaenoic acid and docosahexaenoic acid were increased in the linolenic-rich diet, indicating that the synthesis or deposition of long-chain n-3 fatty acids was accelerated after CLA feeding. The increased docosahexaenoic acid and eicosapentaenoic acid contents in lipid may be compensation for the decreased arachidonic acid content. Dietary supplementation of linoleic acid increased n-6 fatty acid levels in lipids, whereas linolenic acid increased n-3 fatty acid levels. Results also suggest that CLA might not be elongated to synthesize long-chain fatty acids in significant amounts. The effect of CLA in reducing the level of n-6 fatty acids and promoting the level of n-3 fatty acids could be related to the biological effects of CLA.
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A new low linolenic acid allele of GmFAD3A gene in soybean PE1690
USDA-ARS?s Scientific Manuscript database
Relative fatty acid content of soybean oil is about 12 % palmitic acid, 4 % stearic acid, 23 % oleic acid, 54 % linoleic acid, and 8 % linolenic acid. To improve oxidative stability and quality of oil, breeding programs have mainly focused on reducing saturated fatty acids, increasing oleic acid, an...
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Amino acid and fatty acid compositions of Rusip from fermented Anchovy fish (Stolephorussp)
NASA Astrophysics Data System (ADS)
Koesoemawardani, D.; Hidayati, S.; Subeki
2018-04-01
Rusip is a typical food of Bangka Belitung Indonesia made from fermented anchovy. This study aims to determine the properties of chemistry, microbiology, composition of amino acids and fatty acids from fermented fish spontaneously and non spontaneously. Spontaneous rusip treatment is done by anchovy fish (Stolephorussp) after cleaning and added salt 25% (w/w) and palm sugar 10% (w/w). While, non-spontaneous rusip is done by adding a culture mixture of Streptococcus, Leuconostoc, and Lactobacillus bacteria 2% (w/v). The materials are then incubated for 2 weeks. The data obtained were then performed t-test at the level of 5%. Spontaneous and non-spontaneous rusip fermentation process showed significant differences in total acid, reducing sugar, salt content, TVN, total lactic acid bacteria, total mold, and total microbial. The dominant amino acid content of spontaneous and non-spontaneous rusip are glutamic acid and aspartic acid, while the dominant fatty acids in spontaneous and non-spontaneous rusip are docosahexaenoic acid, palmitic acid, oleic acid, arachidonic acid, stearic acid, eicosapentaenoic acid, palmitoleic acid, and myristic acid.
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Synthesis of new kojic acid based unnatural α-amino acid derivatives.
Balakrishna, C; Payili, Nagaraju; Yennam, Satyanarayana; Uma Devi, P; Behera, Manoranjan
2015-11-01
An efficient method for the preparation of kojic acid based α-amino acid derivatives by alkylation of glycinate schiff base with bromokojic acids have been described. Using this method, mono as well as di alkylated kojic acid-amino acid conjugates have been prepared. This is the first synthesis of C-linked kojic acid-amino acid conjugate where kojic acid is directly linked to amino acid through a C-C bond. Copyright © 2015 Elsevier Ltd. All rights reserved.
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HPLC method for the simultaneous quantification of the major organic acids in Angeleno plum fruit
NASA Astrophysics Data System (ADS)
Wang, Yanwei; Wang, Jing; Cheng, Wei; Zhao, Zhilei; Cao, Jiankang
2014-08-01
A method was developed to profile major organic acids in Angeleno fruit by high performance liquid chromatography. Organic acids in plum were extracted by water with ultra- sonication at 50°C for 30 min. The extracts were chromatographed on Waters Atlantis T3 C18 column (4.6 mm×250 mm, 5 μm) with 0.01mol/L sulfuric acid and water as mobile phase, and flow rate was 0.5 ml/min. The column temperature was 40C, and chromatography was monitored by a diode array detector at 210 nm. The result showed that malic acid, citric acid, tartaric acid, oxalic acid, pyruvic acid, acetic acid, succinic acid in Angeleno plum, and the malic acid was the major organic acids. The coefficient of determination of the standard calibration curve is R2 > 0.999. The organic acids recovery ranged from 99.11% for Malic acid to 106.70% for Oxalic acid, and CV (n=6) ranged from 0.95% for Malic acid to 6.23% for Oxalic acid, respectively. The method was accurate, sensitive and feasible in analyzing the organic acids in Angeleno plum.
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Microorganisms for producing organic acids
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pfleger, Brian Frederick; Begemann, Matthew Brett
Organic acid-producing microorganisms and methods of using same. The organic acid-producing microorganisms comprise modifications that reduce or ablate AcsA activity or AcsA homolog activity. The modifications increase tolerance of the microorganisms to such organic acids as 3-hydroxypropionic acid, acrylic acid, propionic acid, lactic acid, and others. Further modifications to the microorganisms increase production of such organic acids as 3-hydroxypropionic acid, lactate, and others. Methods of producing such organic acids as 3-hydroxypropionic acid, lactate, and others with the modified microorganisms are provided. Methods of using acsA or homologs thereof as counter-selectable markers are also provided.
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Microorganisms for producing organic acids
Pfleger, Brian Frederick; Begemann, Matthew Brett
2014-09-30
Organic acid-producing microorganisms and methods of using same. The organic acid-producing microorganisms comprise modifications that reduce or ablate AcsA activity or AcsA homolog activity. The modifications increase tolerance of the microorganisms to such organic acids as 3-hydroxypropionic acid, acrylic acid, propionic acid, lactic acid, and others. Further modifications to the microorganisms increase production of such organic acids as 3-hydroxypropionic acid, lactate, and others. Methods of producing such organic acids as 3-hydroxypropionic acid, lactate, and others with the modified microorganisms are provided. Methods of using acsA or homologs thereof as counter-selectable markers are also provided.
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27 CFR 24.182 - Use of acid to correct natural deficiencies.
Code of Federal Regulations, 2014 CFR
2014-04-01
... acid, fumaric acid, malic acid, lactic acid or tartaric acid, or a combination of two or more of these... citric acid for other fruit (including berries). (d) Other use of acid. A winemaker desiring to use an... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Use of acid to correct...
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27 CFR 24.182 - Use of acid to correct natural deficiencies.
Code of Federal Regulations, 2011 CFR
2011-04-01
... acid, fumaric acid, malic acid, lactic acid or tartaric acid, or a combination of two or more of these... citric acid for other fruit (including berries). (d) Other use of acid. A winemaker desiring to use an... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Use of acid to correct...
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27 CFR 24.182 - Use of acid to correct natural deficiencies.
Code of Federal Regulations, 2012 CFR
2012-04-01
... acid, fumaric acid, malic acid, lactic acid or tartaric acid, or a combination of two or more of these... citric acid for other fruit (including berries). (d) Other use of acid. A winemaker desiring to use an... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Use of acid to correct...
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27 CFR 24.182 - Use of acid to correct natural deficiencies.
Code of Federal Regulations, 2013 CFR
2013-04-01
... acid, fumaric acid, malic acid, lactic acid or tartaric acid, or a combination of two or more of these... citric acid for other fruit (including berries). (d) Other use of acid. A winemaker desiring to use an... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Use of acid to correct...
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Acid Rain: What It Is -- How You Can Help!
ERIC Educational Resources Information Center
National Wildlife Federation, Washington, DC.
This publication discusses the nature and consequences of acid precipitation (commonly called acid rain). Topic areas include: (1) the chemical nature of acid rain; (2) sources of acid rain; (3) geographic areas where acid rain is a problem; (4) effects of acid rain on lakes; (5) effect of acid rain on vegetation; (6) possible effects of acid rain…
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NASA Astrophysics Data System (ADS)
Yamamoto, Hideki; Sumoge, Iwao
2011-03-01
This study presents the distillation separation of hydrofluoric acid with use of the salt effect on the vapor-liquid equilibrium for acid aqueous solutions and acid mixtures. The vapor-liquid equilibrium of hydrofluoric acid + salt systems (fluorite, potassium nitrate, cesium nitrate) was measured using an apparatus made of perfluoro alkylvinylether. Cesium nitrate showed a salting-out effect on the vapor-liquid equilibrium of the hydrofluoric acid-water system. Fluorite and potassium nitrate showed a salting-in effect on the hydrofluoric acid-water system. Separation of hydrofluoric acid from an acid mixture containing nitric acid and hydrofluoric acid was tested by the simple distillation treatment using the salt effect of cesium nitrate (45 mass%). An acid mixture of nitric acid (5.0 mol · dm-3) and hydrofluoric acid (5.0 mol · dm-3) was prepared as a sample solution for distillation tests. The concentration of nitric acid in the first distillate decreased from 5.0 mol · dm-3 to 1.13 mol · dm-3, and the concentration of hydrofluoric acid increased to 5.41 mol · dm-3. This first distillate was further distilled without the addition of salt. The concentrations of hydrofluoric acid and nitric acid in the second distillate were 7.21 mol · dm-3 and 0.46 mol · dm-3, respectively. It was thus found that the salt effect on vapor-liquid equilibrium of acid mixtures was effective for the recycling of acids from acid mixture wastes.
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Li, Zhou; Yu, Jingjin; Peng, Yan; Huang, Bingru
2017-01-01
Abscisic acid (ABA), salicylic acid (SA) and γ-aminobutyric acid (GABA) are known to play roles in regulating plant stress responses. This study was conducted to determine metabolites and associated pathways regulated by ABA, SA and GABA that could contribute to drought tolerance in creeping bentgrass (Agrostis stolonifera). Plants were foliar sprayed with ABA (5 μM), GABA (0.5 mM) and SA (10 μM) or water (untreated control) prior to 25 days drought stress in controlled growth chambers. Application of ABA, GABA or SA had similar positive effects on alleviating drought damages, as manifested by the maintenance of lower electrolyte leakage and greater relative water content in leaves of treated plants relative to the untreated control. Metabolic profiling showed that ABA, GABA and SA induced differential metabolic changes under drought stress. ABA mainly promoted the accumulation of organic acids associated with tricarboxylic acid cycle (aconitic acid, succinic acid, lactic acid and malic acid). SA strongly stimulated the accumulation of amino acids (proline, serine, threonine and alanine) and carbohydrates (glucose, mannose, fructose and cellobiose). GABA enhanced the accumulation of amino acids (GABA, glycine, valine, proline, 5-oxoproline, serine, threonine, aspartic acid and glutamic acid) and organic acids (malic acid, lactic acid, gluconic acid, malonic acid and ribonic acid). The enhanced drought tolerance could be mainly due to the enhanced respiration metabolism by ABA, amino acids and carbohydrates involved in osmotic adjustment (OA) and energy metabolism by SA, and amino acid metabolism related to OA and stress-defense secondary metabolism by GABA. © 2016 Scandinavian Plant Physiology Society.
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Murakami, Nao; Oba, Mana; Iwamoto, Mariko; Tashiro, Yukihiro; Noguchi, Takuya; Bonkohara, Kaori; Abdel-Rahman, Mohamed Ali; Zendo, Takeshi; Shimoda, Mitsuya; Sakai, Kenji; Sonomoto, Kenji
2016-01-01
Glycerol is a by-product in the biodiesel production process and considered as one of the prospective carbon sources for microbial fermentation including lactic acid fermentation, which has received considerable interest due to its potential application. Enterococcus faecalis isolated in our laboratory produced optically pure L-lactic acid from glycerol in the presence of acetic acid. Gas chromatography-mass spectrometry analysis using [1, 2-(13)C2] acetic acid proved that the E. faecalis strain QU 11 was capable of converting acetic acid to ethanol during lactic acid fermentation of glycerol. This indicated that strain QU 11 restored the redox balance by oxidizing excess NADH though acetic acid metabolism, during ethanol production, which resulted in lactic acid production from glycerol. The effects of pH control and substrate concentration on lactic acid fermentation were also investigated. Glycerol and acetic acid concentrations of 30 g/L and 10 g/L, respectively, were expected to be appropriate for lactic acid fermentation of glycerol by strain QU 11 at a pH of 6.5. Furthermore, fed-batch fermentation with 30 g/L glycerol and 10 g/L acetic acid wholly exhibited the best performance including lactic acid production (55.3 g/L), lactic acid yield (0.991 mol-lactic acid/mol-glycerol), total yield [1.08 mol-(lactic acid and ethanol)]/mol-(glycerol and acetic acid)], and total carbon yield [1.06 C-mol-(lactic acid and ethanol)/C-mol-(glycerol and acetic acid)] of lactic acid and ethanol. In summary, the strain QU 11 successfully produced lactic acid from glycerol with acetic acid metabolism, and an efficient fermentation system was established without carbon loss. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.
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Acid-functionalized polyolefin materials and their use in acid-promoted chemical reactions
DOE Office of Scientific and Technical Information (OSTI.GOV)
Oyola, Yatsandra; Tian, Chengcheng; Bauer, John Christopher
An acid-functionalized polyolefin material that can be used as an acid catalyst in a wide range of acid-promoted chemical reactions, wherein the acid-functionalized polyolefin material includes a polyolefin backbone on which acid groups are appended. Also described is a method for the preparation of the acid catalyst in which a precursor polyolefin is subjected to ionizing radiation (e.g., electron beam irradiation) of sufficient power and the irradiated precursor polyolefin reacted with at least one vinyl monomer having an acid group thereon. Further described is a method for conducting an acid-promoted chemical reaction, wherein an acid-reactive organic precursor is contacted inmore » liquid form with a solid heterogeneous acid catalyst comprising a polyolefin backbone of at least 1 micron in one dimension and having carboxylic acid groups and either sulfonic acid or phosphoric acid groups appended thereto.« less
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Christie, William W.; Hunter, Margaret L.
1980-01-01
The effects of inclusion of different fatty acids in the medium on the rate of esterification of palmitic acid and its stereospecific distribution among the three positions of the triacyl-sn-glycerols by preparations of rat adipocytes in vitro have been determined. Myristic acid, stearic acid, oleic acid and linoleic acid were used as diluents and the concentration of the combined unesterified fatty acids in the medium was held constant; only the proportion of palmitic acid was varied. The amount of palmitic acid esterified was always linearly related to its relative concentration in the medium and was not significantly affected by the nature of the diluent fatty acid chosen. Constant relative proportions were recovered in triacylglycerols and in intermediates in each instance. The amount of palmitic acid esterified to each of the positions of the triacyl-sn-glycerols was linearly dependent on the relative proportion in the medium but the nature of the relationship was markedly influenced by which fatty acid was present. When stearic acid was present, simple relationships were found over the whole range tested. When either myristic acid, oleic acid or linoleic acid was present, abrupt changes in the manner of esterification of palmitic acid were observed in position sn-1 when the relative concentrations of palmitic acid and the diluent reached critical values, which differed with each fatty acid. In position sn-2 when oleic acid or linoleic acid was present, a similar change was observed, and in position sn-3 it was obtained with myristic acid as diluent. The results are discussed in terms of changes in the relative affinities of the acyltransferases for palmitic acid. Palmitic acid was esterified into various molecular species in proportions that indicated acylation with non-correlative specificity at higher relative concentrations but not at lower. PMID:7236215
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Phenylpropanoid Metabolism in Suspension Cultures of Vanilla planifolia Andr. 1
Funk, Christoph; Brodelius, Peter E.
1990-01-01
Feeding of 4-methoxycinnamic acid, 3,4-dimethoxycinnamic acid and 3,4,5-trimethoxycinnamic acid to cell suspension cultures of Vanilla planifolia resulted in the formation of 4-hydroxybenzoic acid, vanillic acid, and syringic acid, respectively. The homologous 4-methoxybenzoic acids were demethylated to the same products. It is concluded that the side chain degrading enzyme system accepts the 4-methoxylated substrates while the demethylation occurs at the benzoic acid level. The demethylating enzyme is specific for the 4-position. Feeding of [O-14C-methyl]-3,4-dimethoxycinnamic acid revealed that the first step in the conversion is the glycosylation of the cinnamic acid to its glucose ester. A partial purification of a UDP-glucose: trans-cinnamic acid glucosyltransferase is reported. 4-Methoxy substituted cinnamic acids are better substrates for this enzyme than 4-hydroxy substituted cinnamic acid. It is suggested that 4-methoxy substituted cinnamic acids are intermediates in the biosynthetic conversion of cinnamic acids to benzoic acids in cells of V. planifolia. PMID:16667674
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Uptake mechanism of valproic acid in human placental choriocarcinoma cell line (BeWo).
Ushigome, F; Takanaga, H; Matsuo, H; Tsukimori, K; Nakano, H; Ohtani, H; Sawada, Y
2001-04-13
Valproic acid is an anticonvulsant widely used for the treatment of epilepsy. However, valproic acid is known to show fetal toxicity, including teratogenicity. In the present study, to elucidate the mechanisms of valproic acid transport across the blood-placental barrier, we carried out transcellular transport and uptake experiments with human placental choriocarcinoma epithelial cells (BeWo cells) in culture. The permeability coefficient of [3H]valproic acid in BeWo cells for the apical-to-basolateral flux was greater than that for the opposite flux, suggesting a higher unidirectional transport in the fetal direction. The uptake of [3H]valproic acid from the apical side was temperature-dependent and enhanced under acidic pH. In the presence of 50 microM carbonyl cyanide p-trifluoromethoxylhydrazone, the uptake of [3H]valproic acid was significantly reduced. A metabolic inhibitor, 10 mM sodium azide, also significantly reduced the uptake of [3H]valproic acid. Therefore, valproic acid is actively transported in a pH-dependent manner on the brush-border membrane of BeWo cells. Kinetic analysis of valproic acid uptake revealed the involvement of a non-saturable component and a saturable component. The Michaelis constant for the saturable transport (K(t)) was smaller under acidic pH, suggesting a proton-linked active transport mechanism for valproic acid in BeWo cells. In the inhibitory experiments, some short-chain fatty acids, such as acetic acid, lactic acid, propanoic acid and butyric acid, and medium-chain fatty acids, such as hexanoic acid and octanoic acid, inhibited the uptake of [3H]valproic acid. The uptake of [3H]valproic acid was also significantly decreased in the presence of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, salicylic acid and furosemide, which are well-known inhibitors of the anion exchange system. Moreover, p-aminohippuric acid significantly reduced the uptake of [3H]valproic acid. These results suggest that an active transport mechanism for valproic acid exists on the brush-border membrane of placental trophoblast cells and operates in a proton-linked manner.
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Lee, Jihyun; Chan, Bronte Lee Shan; Mitchell, Alyson E
2017-01-15
Free and bound phenolic acids were measured in the pulp and peel of four varieties of apples using high resolution mass spectrometry. Twenty-five phenolic acids were identified and included: 8 hydroxybenzoic acids, 11 hydroxycinnamic acids, 5 hydroxyphenylacetic acids, and 1 hydoxyphenylpropanoic acid. Several phenolics are tentatively identified for the first time in apples and include: methyl gallate, ethyl gallate, hydroxy phenyl acetic acid, three phenylacetic acid isomers, 3-(4-hydroxyphenyl)propionic acid, and homoveratric acid. With exception of chlorogenic and caffeic acid, most phenolic acids were quantified for the first time in apples. Significant varietal differences (p<0.05) were observed in both peel and pulp. The levels of total phenolic acids were higher in the pulp as compared to apple peel (dry weight) in all varieties. Coumaroylquinic, protocatechuic, 4-hydroxybenzoic, vanillic and t-ferulic acids were present in free forms. With exception of chlorogenic acid, all other phenolic acids were present only as bound forms. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Xu, Jian; Bao, Jia-Wei; Su, Xian-Feng; Zhang, Hong-Jian; Zeng, Xin; Tang, Lei; Wang, Ke; Zhang, Jian-Hua; Chen, Xu-Sheng; Mao, Zhong-Gui
2016-03-01
In this study, an integrated citric acid-methane fermentation process was established to solve the problem of wastewater treatment in citric acid production. Citric acid wastewater was treated through anaerobic digestion and then the anaerobic digestion effluent (ADE) was further treated and recycled for the next batch citric acid fermentation. This process could eliminate wastewater discharge and reduce water resource consumption. Propionic acid was found in the ADE and its concentration continually increased in recycling. Effect of propionic acid on citric acid fermentation was investigated, and results indicated that influence of propionic acid on citric acid fermentation was contributed to the undissociated form. Citric acid fermentation was inhibited when the concentration of propionic acid was above 2, 4, and 6 mM in initial pH 4.0, 4.5 and, 5.0, respectively. However, low concentration of propionic acid could promote isomaltase activity which converted more isomaltose to available sugar, thereby increasing citric acid production. High concentration of propionic acid could influence the vitality of cell and prolong the lag phase, causing large amount of glucose still remaining in medium at the end of fermentation and decreasing citric acid production.
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Mitsuya, Daisuke; Hayashi, Takuya; Wang, Yu; Tanaka, Mami; Okai, Masahiko; Ishida, Masami; Urano, Naoto
2017-07-01
The Yukawa River is an extremely acidic river whose waters on the east foot of the Kusatu-Shirane Volcano (in Gunma Prefecture, Japan) contain sulfate ions. Here we isolated many acid-tolerant yeasts from the Yukawa River, and some of them neutralized an acidic R2A medium containing casamino acid. Candida fluviatilis strain CeA16 had the strongest acid tolerance and neutralizing activity against the acidic medium. To clarify these phenomena, we performed neutralization tests with strain CeA16 using casamino acid, a mixture of amino acids, and 17 single amino acid solutions adjusted to pH 3.0, respectively. Strain CeA16 neutralized not only acidic casamino acid and the mixture of amino acids but also some of the acidic single amino acid solutions. Seven amino acids were strongly decomposed by strain CeA16 and simultaneously released ammonium ions. These results suggest strain CeA16 is a potential yeast as a new tool to neutralize acidic environments. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.
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Liao, James C.; Cho, Kwang Myung; Yan, Yajun; Huo, Yixin
2016-03-15
Provided herein are metabolically modified microorganisms characterized by having an increased keto-acid flux when compared with the wild-type organism and comprising at least one polynucleotide encoding an enzyme that when expressed results in the production of a greater quantity of a chemical product when compared with the wild-type organism. The recombinant microorganisms are useful for producing a large number of chemical compositions from various nitrogen containing biomass compositions and other carbon sources. More specifically, provided herein are methods of producing alcohols, acetaldehyde, acetate, isobutyraldehyde, isobutyric acid, n-butyraldehyde, n-butyric acid, 2-methyl-1-butyraldehyde, 2-methyl-1-butyric acid, 3-methyl-1-butyraldehyde, 3-methyl-1-butyric acid, ammonia, ammonium, amino acids, 2,3-butanediol, 1,4-butanediol, 2-methyl-1,4-butanediol, 2-methyl-1,4-butanediamine, isobutene, itaconate, acetoin, acetone, isobutene, 1,5-diaminopentane, L-lactic acid, D-lactic acid, shikimic acid, mevalonate, polyhydroxybutyrate (PHB), isoprenoids, fatty acids, homoalanine, 4-aminobutyric acid (GABA), succinic acid, malic acid, citric acid, adipic acid, p-hydroxy-cinnamic acid, tetrahydrofuran, 3-methyl-tetrahydrofuran, gamma-butyrolactone, pyrrolidinone, n-methylpyrrolidone, aspartic acid, lysine, cadeverine, 2-ketoadipic acid, and/or S-adenosyl-methionine (SAM) from a suitable nitrogen rich biomass.
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Haling, Rebecca E; Simpson, Richard J; Culvenor, Richard A; Lambers, Hans; Richardson, Alan E
2011-03-01
It is unclear whether roots of acid-soil resistant plants have significant advantages, compared with acid-soil sensitive genotypes, when growing in high-strength, acid soils or in acid soils where macropores may allow the effects of soil acidity and strength to be avoided. The responses of root growth and morphology to soil acidity, soil strength and macropores by seedlings of five perennial grass genotypes differing in acid-soil resistance were determined, and the interaction of soil acidity and strength for growth and morphology of roots was investigated. Soil acidity and strength altered root length and architecture, root hair development, and deformed the root tip, especially in acid-soil sensitive genotypes. Root length was restricted to some extent by soil acidity in all genotypes, but the adverse impact of soil acidity on root growth by acid-soil resistant genotypes was greater at high levels of soil strength. Roots reacted to soil acidity when growing in macropores, but elongation through high-strength soil was improved. Soil strength can confound the effect of acidity on root growth, with the sensitivity of acid-resistant genotypes being greater in high-strength soils. This highlights the need to select for genotypes that resist both acidity and high soil strength. © 2010 Blackwell Publishing Ltd.
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Liu, Songling; Ren, Fazheng; Jiang, Jingli; Zhao, Liang
2016-07-28
The acid response of Bifidobacterium longum subsp. longum BBMN68 has been studied in our previous study. The fab gene, which is supposed to be involved in membrane fatty acid biosynthesis, was demonstrated to be induced in acid response. In order to investigate the relationship between acid response and cell membrane fatty acid composition, the acid adaptation of BBMN68 was assessed and the membrane fatty acid composition at different adaptation conditions was identified. Indeed, the fatty acid composition was influenced by acid adaptation. Our results showed that the effective acid adaptations were accompanied with decrease in the unsaturated to saturated fatty acids ratio (UFA/SFA) and increase in cyclopropane fatty acid (CFA) content, which corresponded to previous studies. Moreover, both effective and non-effective acid adaptation conditions resulted in decrease in the C18:1 cis-9/C18:1 trans-9 ratio, indicating that the C18:1 cis-9/C18:1 trans-9 ratio is associated with acid tolerance response but not with acid adaptation response. Taken together, this study indicated that the UFA/SFA and CFA content of BBMN68 were involved in acid adaptation and the C18:1 cis-9/C18:1 trans-9 ratio was involved in acid tolerance response.
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Piazzon, A; Vrhovsek, U; Masuero, D; Mattivi, F; Mandoj, F; Nardini, M
2012-12-19
The main metabolites of caffeic and ferulic acids (ferulic acid-4'-O-sulfate, caffeic acid-4'-O-sulfate, and caffeic acid-3'-O-sulfate), the most representative phenolic acids in fruits and vegetables, and the acyl glucuronide of ferulic acid were synthesized, purified, and tested for their antioxidant activity in comparison with those of their parent compounds and other related phenolics. Both the ferric reducing antioxidant power (FRAP) assay and the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging method were used. Ferulic acid-4'-O-sulfate and ferulic acid-4'-O-glucuronide exhibited very low antioxidant activity, while the monosulfate derivatives of caffeic acid were 4-fold less efficient as the antioxidant than caffeic acid. The acyl glucuronide of ferulic acid showed strong antioxidant action. The antioxidant activity of caffeic acid-3'-O-glucuronide and caffeic acid-4'-O-glucuronide was also studied. Our results demonstrate that some of the products of phenolic acid metabolism still retain strong antioxidant properties. Moreover, we first demonstrate the ex vivo synthesis of the acyl glucuronide of ferulic acid by mouse liver microsomes, in addition to the phenyl glucuronide.
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Bae, Jae-Han; Kim, Deuk-Soo; Suh, Min-Jung; Oh, Sei-Ryang; Lee, In-Jung; Kang, Sun-Chul; Hou, Ching T; Kim, Hak-Ryul
2007-05-01
Hydroxy fatty acids are considered as important value-added product for industrial application because of their special properties such as higher viscosity and reactivity. Microbial production of the hydroxy fatty acids from various fatty acid substrates have been actively studied using several microorganisms. The new bacterial isolate Pseudomonas aeruginosa (PR3) had been reported to produce mono-, di-, and tri-hydroxy fatty acids from different unsaturated fatty acids. Of those, 7,10-dihydroxy-8(E)-octadecenoic acid (DOD) and 7,10,12-trihydroxy-8(E)-octadecenoic acid (TOD) were produced from oleic acid and ricinoleic acid, respectively. Based on the postulated common metabolic pathway involved in DOD and TOD formation by PR3, it was assumed that palmitoleic acid containing a singular 9-cis double bond, common structural property sharing with oleic acid and ricinoleic acid, could be utilized by PR3 to produce hydroxy fatty acid. In this study, we tried to use palmitoleic acid as substrate for production of hydroxy fatty acid by PR3 and firstly confirmed that PR3 could produce 7,10-dihydroxy-8(E)-hexadecenoic acid (DHD) with 23% yield from palmitoleic acid. DHD production was peaked at 72 h after the substrate was added to the 24-h-culture.
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[Studies on interaction of acid-treated nanotube titanic acid and amino acids].
Zhang, Huqin; Chen, Xuemei; Jin, Zhensheng; Liao, Guangxi; Wu, Xiaoming; Du, Jianqiang; Cao, Xiang
2010-06-01
Nanotube titanic acid (NTA) has distinct optical and electrical character, and has photocatalysis character. In accordance with these qualities, NTA was treated with acid so as to enhance its surface activity. Surface structures and surface groups of acid-treated NTA were characterized and analyzed by Transmission Electron Microscope (TEM) and Fourier Transform Infrared Spectrometry (FT-IR). The interaction between acid-treated NTA and amino acids was investigated. Analysis results showed that the lengths of acid-treated NTA became obviously shorter. The diameters of nanotube bundles did not change obviously with acid-treating. Meanwhile, the surface of acid-treated NTA was cross-linked with carboxyl or esterfunction. In addition, acid-treated NTA can catch amino acid residues easily, and then form close combination.
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AGARD Corrosion Handbook. Volume 1. Aircraft Corrosion: Causes and Case Histories
1985-07-01
Anodic coatings can be formed in chromic acid, sulphuric acid, phosphoric acid or oxalic acid solutions. Chromic acid anodizing is widely used with...and consists of a thin non-porous barrier layer next to the metal with a porous outer layer that can be sealed by hydrothermal treatment in steam...anaerobic) or an oxidative (aerobic) mechanism. Various organic acids such as citric acid, oxalic acid, gluconic acid, dodecanoic acid, etc., which may be
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Prasadani, W. Chaturi; Senanayake, Chaturi M.; Jayathilaka, Nimanthi; Ekanayake, Sagarika
2017-01-01
Polyphenolic antioxidants are mainly absorbed through passive paracellular permeation regulated by tight junctions. Some fatty acids are known to modulate tight junctions. Fatty acids resulting from the digestion of edible oils may improve the absorption of polyphenolic antioxidants. Therefore, we explored the effect of three edible oils on the intestinal absorption of caffeic acid. Rats were fed with soybean oil and caffeic acid dissolved in distilled water. Caffeic acid contents in the plasma collected up to 1 hr were quantified. The experiment was repeated with coconut oil and olive oil. Component fatty acids of the oils were individually tested in vitro for their effect on permeability of caffeic acid using Caco-2 cell monolayers. Highest absorption of caffeic acid was observed in animals fed with coconut oil. In vitro transport percentages of caffeic acid in 2.5 mmol/L solutions of fatty acids were 22.01±0.12 (lauric), 15.30 ± 0.25 (myristic acid), 13.59 ± 0.35 (linoleic acid), 3.70 ± 0.09 (oleic acid) and 0.10–2.0 (all other fatty acids). Lauric acid and myristic acid are the two major fatty acids present in coconut oil. Therefore, these fatty acids may contribute to the higher absorption of caffeic acid in the presence of coconut oil. PMID:28617858
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Electrophilic properties of common MALDI matrix molecules
NASA Astrophysics Data System (ADS)
Lippa, T. P.; Eustis, S. N.; Wang, D.; Bowen, K. H.
2007-11-01
The negative ion photoelectron spectra of the following MALDI matrix molecules have been measured: 3-carboxypyridine (nicotinic acid), 2,5-dihydroxybenzoic acid (DHB), 3,5-dimethoxy-4-hydroxycinnamic acid (sinapinic acid), 2,6-dihydroxyacetophenone (DHAP), 3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid (ferulic acid), 3-hydroxy-2-pyridinecarboxylic acid (3HPA), and 2,6-pyridinedicarboxylic acid (dipicolinic acid). Adiabatic electron affinities and vertical detachment energies were extracted from these spectra and reported. In addition, electron affinities were calculated for DHAP, ferulic acid, dipicolinic acid and sinapinic acid. Photoelectron spectra were also measured for the dimer anions of DHB and nicotinic acid and for the fragment anion in which alpha-cyano-cinnamic acid had lost a CO2 unit. Together, these results augment the database of presently available electrophilic data on common matrix molecules along with some of their dimers and fragments.
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Li, Xiukai; Zhang, Yugen
2016-10-06
The deoxydehydration (DODH) of sugar acids to industrially important carboxylic acids is a very attractive topic. Oxorhenium complexes are the most-often employed DODH catalysts. Because of the acidity of the rhenium catalysts, the DODH products of sugar acids were usually in the form of mixture of free carboxylic acids and esters. Herein, we demonstrate strategies for the selective DODH of sugar acids to free carboxylic acids by tuning the Lewis acidity or the Brønsted acidity of the rhenium-based catalysts. Starting from tartaric acid, up to 97 % yield of free maleic acid was achieved. Based on our strategies, functional polymer immobilized heterogeneous rhenium catalysts were also developed for the selective DODH conversion of sugar acids. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Albishri, Hassan M; Almaghrabi, Omar A; Moussa, Tarek A A
2013-01-01
The growth in the production of biodiesel, which is principally fatty acid methyl esters (FAME), has been phenomenal in the last ten years because of the general desire to cut down on the release of greenhouse gases into the atmosphere, and also as a result of the increasing cost of fossil fuels. Establish whether there is any relationship between two different species (watermelon and muskmelon) within the same family (Cucurbitaceae) on fatty acid compositions and enumerate the different fatty acids in the two species. Extraction of fatty acids from the two species and preparation the extract to gas chromatography/mass spectroscopy analysis to determine the fatty acids compositions qualitatively and quantitatively. The analyzed plants (watermelon and muskmelon) contain five saturated fatty acids; tetrdecanoic acid, pentadecanoic acid, hexadecanoic acid, heptadecanoic acid and octadecanoic acid with different concentrations, while muskmelon contains an extra saturated fatty acid named eicosanoic acid. The watermelon plant contains five unsaturated fatty acids while muskmelon contains three only, the two plants share in two unsaturated fatty acids named 9-hexadecenoic acid and 9-octadecenoic acid, the muskmelon plant contains higher amounts of these two acids (2.04% and 10.12%, respectively) over watermelon plant (0.88% and 0.25%, respectively). The chemical analysis of watermelon and muskmelon revealed that they are similar in saturated fatty acids but differ in unsaturated fatty acids which may be a criterion of differentiation between the two plants.
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ω-Alkynyl lipid surrogates for polyunsaturated fatty acids: free radical and enzymatic oxidations.
Beavers, William N; Serwa, Remigiusz; Shimozu, Yuki; Tallman, Keri A; Vaught, Melissa; Dalvie, Esha D; Marnett, Lawrence J; Porter, Ned A
2014-08-13
Lipid and lipid metabolite profiling are important parameters in understanding the pathogenesis of many diseases. Alkynylated polyunsaturated fatty acids are potentially useful probes for tracking the fate of fatty acid metabolites. The nonenzymatic and enzymatic oxidations of ω-alkynyl linoleic acid and ω-alkynyl arachidonic acid were compared to that of linoleic and arachidonic acid. There was no detectable difference in the primary products of nonenzymatic oxidation, which comprised cis,trans-hydroxy fatty acids. Similar hydroxy fatty acid products were formed when ω-alkynyl linoleic acid and ω-alkynyl arachidonic acid were reacted with lipoxygenase enzymes that introduce oxygen at different positions in the carbon chains. The rates of oxidation of ω-alkynylated fatty acids were reduced compared to those of the natural fatty acids. Cyclooxygenase-1 and -2 did not oxidize alkynyl linoleic but efficiently oxidized alkynyl arachidonic acid. The products were identified as alkynyl 11-hydroxy-eicosatetraenoic acid, alkynyl 11-hydroxy-8,9-epoxy-eicosatrienoic acid, and alkynyl prostaglandins. This deviation from the metabolic profile of arachidonic acid may limit the utility of alkynyl arachidonic acid in the tracking of cyclooxygenase-based lipid oxidation. The formation of alkynyl 11-hydroxy-8,9-epoxy-eicosatrienoic acid compared to alkynyl prostaglandins suggests that the ω-alkyne group causes a conformational change in the fatty acid bound to the enzyme, which reduces the efficiency of cyclization of dioxalanyl intermediates to endoperoxide intermediates. Overall, ω-alkynyl linoleic acid and ω-alkynyl arachidonic acid appear to be metabolically competent surrogates for tracking the fate of polyunsaturated fatty acids when looking at models involving autoxidation and oxidation by lipoxygenases.
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Cadmium Alters the Concentration of Fatty Acids in THP-1 Macrophages.
Olszowski, Tomasz; Gutowska, Izabela; Baranowska-Bosiacka, Irena; Łukomska, Agnieszka; Drozd, Arleta; Chlubek, Dariusz
2018-03-01
Fatty acid composition of human immune cells influences their function. The aim of this study was to evaluate the effects of known toxicant and immunomodulator, cadmium, at low concentrations on levels of selected fatty acids (FAs) in THP-1 macrophages. The differentiation of THP-1 monocytes into macrophages was achieved by administration of phorbol myristate acetate. Macrophages were incubated with various cadmium chloride (CdCl 2 ) solutions for 48 h at final concentrations of 5 nM, 20 nM, 200 nM, and 2 μM CdCl 2 . Fatty acids were extracted from samples according to the Folch method. The fatty acid levels were determined using gas chromatography. The following fatty acids were analyzed: long-chain saturated fatty acids (SFAs) palmitic acid and stearic acid, very long-chain saturated fatty acid (VLSFA) arachidic acid, monounsaturated fatty acids (MUFAs) palmitoleic acid, oleic acid and vaccenic acid, and n-6 polyunsaturated fatty acids (PUFAs) linoleic acid and arachidonic acid. Treatment of macrophages with very low concentrations of cadmium (5-200 nM) resulted in significant reduction in the levels of arachidic, palmitoleic, oleic, vaccenic, and linoleic acids and significant increase in arachidonic acid levels (following exposure to 5 nM Cd), without significant reduction of palmitic and stearic acid levels. Treatment of macrophages with the highest tested cadmium concentration (2 μM) produced significant reduction in the levels of all examined FAs: SFAs, VLSFA, MUFAs, and PUFAs. In conclusion, cadmium at tested concentrations caused significant alterations in THP-1 macrophage fatty acid levels, disrupting their composition, which might dysregulate fatty acid/lipid metabolism thus affecting macrophage behavior and inflammatory state.
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Xu, Xianghuai; Yang, Zhongmin; Chen, Qiang; Yu, Li; Liang, Siwei; Lü, Hanjing; Qiu, Zhongmin
2015-04-01
Little is known about non-acid gastroesophageal reflux-induced chronic cough (GERC). The purpose of the study is to explore the clinical characteristics of non-acid GERC. Clinical symptoms, cough symptom score, capsaicin cough sensitivity, gastroesophageal reflux diagnostic questionnaire (GerdQ) score, findings of multichannel intraluminal impedance-pH monitoring (MII-pH) and response to pharmacological anti-reflux therapy were retrospectively reviewed in 38 patients with non-acid GERC and compared with those of 49 patients with acid GERC. Non-acid GERC had the similar cough character, cough symptom score, and capsaicin cough sensitivity to acid GERC. However, non-acid GERC had less frequent regurgitation (15.8% vs 57.1%, χ(2) = 13.346, P = 0.000) and heartburn (7.9% vs 32.7%, χ(2) = 7.686, P = 0.006), and lower GerdQ score (7.4 ± 1.4 vs 10.6 ± 2.1, t = -6.700, P = 0.003) than acid GERC. Moreover, MII-pH revealed more weakly acidic reflux episodes, gas reflux episodes and a higher symptom association probability (SAP) for non-acid reflux but lower DeMeester score, acidic reflux episodes and SAP for acid reflux in non-acid GERC than in acid GERC. Non-acid GERC usually responded to the standard anti-reflux therapy but with delayed cough resolution or attenuation when compared with acid GERC. Fewer patients with non-acid GERC needed an augmented acid suppressive therapy or treatment with baclofen. There are some differences in the clinical manifestations between non-acid and acid GERC, but MII-pH is essential to diagnose non-acid GERC. © 2014 John Wiley & Sons Ltd.
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Bricker, Owen P.; Rice, Karen C.
1995-01-01
Although acid rain is fading as a political issue in the United States and funds for research in this area have largely disappeared, the acidity of rain in the Eastern United States has not changed significantly over the last decade, and it continues to be a serious environmental problem. Acid deposition (commonly called acid rain) is a term applied to all forms of atmospheric deposition of acidic substances - rain, snow, fog, acidic dry particulates, aerosols, and acid-forming gases. Water in the atmosphere reacts with certain atmospheric gases to become acidic. For example, water reacts with carbon dioxide in the atmosphere to produce a solution with a pH of about 5.6. Gases that produce acids in the presence of water in the atmosphere include carbon dioxide (which converts to carbonic acid), oxides of sulfur and nitrogen (which convert to sulfuric and nitric acids}, and hydrogen chloride (which converts to hydrochloric acid). These acid-producing gases are released to the atmosphere through natural processes, such as volcanic emissions, lightning, forest fires, and decay of organic matter. Accordingly, precipitation is slightly acidic, with a pH of 5.0 to 5.7 even in undeveloped areas. In industrialized areas, most of the acid-producing gases are released to the atmosphere from burning fossil fuels. Major emitters of acid-producing gases include power plants, industrial operations, and motor vehicles. Acid-producing gases can be transported through the atmosphere for hundreds of miles before being converted to acids and deposited as acid rain. Because acids tend to build up in the atmosphere between storms, the most acidic rain falls at the beginning of a storm, and as the rain continues, the acids "wash out" of the atmosphere.
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Chicoric Acid Found in Basil (Ocimum basilicum L.) Leaves
USDA-ARS?s Scientific Manuscript database
This is the first report to identify the presence of chicoric acid (cichoric acid; also known as dicaffeoyltartaric acid) in basil leaves. Rosmarinic acid, chicoric acid, and caftaric acid (in the order of most abundant to least; all derivatives of caffeic acid) were identified in fresh basil leaves...
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Acute Toxicity of a Number of Chemicals of Interest to the Air Force
1979-03-01
Acid Azelaic Acid Dimer Acid N-Benzyl-3, 7-Dioctyl Phenothiazine Phenothiazine Dioctyl Phenothiazine Sebacic Acid ...liquid) 1,4-dihydroxyanthraquinone (solid) Sulfurized 9-octadecenoic acid (liquid) Azelaic acid (solid) Dimer acid (liquid) N-benzyl-3,7-dicotyl...dihydroxyanthra- Rat >5000 5000(0) Below Toxic quinone Sulfurized 9-octa- Rat >5000 5000(0) Below Toxic decenoic acid Azelaic acid Rat >5000
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Comparative fatty acid composition of four Sargassum species (Fucales, Phaeophyta)
NASA Astrophysics Data System (ADS)
Wu, Xiang-Chun; Lu, Bao-Ren; Tseng, C. K.
1995-12-01
Fatty acid composition of four Sargassum species from Qingdao and Shidao, Shandong Province was investigated. 16:0 (palmitic acid) was the major saturated fatty acid. C18 and C20 were the main polyunsaturated fatty acids (PUFAs). Arachidonic acid and eicosapentaenoic acid predominated among polyenoic acids in all the algal species examined, except for Sargassum sp. which had low concentration of eicosapentaenoic acid.
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Wang, Lei; Murai, Yuta; Yoshida, Takuma; Okamoto, Masashi; Tachrim, Zetryana Puteri; Hashidoko, Yasuyuki; Hashimoto, Makoto
2014-05-16
Aryl-keto-containing α-amino acids are of great importance in organic chemistry and biochemistry. They are valuable intermediates for the construction of hydroxyl α-amino acids, nonproteinogenic α-amino acids, as well as other biofunctional components. Friedel-Crafts acylation is an effective method to prepare aryl-keto derivatives. In this review, we summarize the preparation of aryl-keto containing α-amino acids by Friedel-Crafts acylation using acidic α-amino acids as acyl-donors and Lewis acids or Brönsted acids as catalysts.
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Omega-3 fatty acids in baked freshwater fish from south of Brazil.
Andrade, A D; Visentainer, J V; Matsushita, M; de Souza, N E
1997-03-01
Lipid and fatty acid levels in the edible flesh of 17 baked freshwater fish from Brazil's southern region were determined. Analyses of fatty acids methyl esters were performed by gas chromatography. Palmitic acid (C16:0) was the predominant saturated fatty acid, accouting for 50-70% of total saturated acids. Linoleic acid (C18:2 omega 6), linolenic acid (C18:3 omega 3), and docosahexaenoic acid (C22:6 omega 3) were the predominant polyunsatured fatty acids (PUFA). The data revealed that species such as barbado, corvina, pintado, and truta were good sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and that most freshwater fish examined were good sources of PUFA-omega 3.
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Yin, Xian; Li, Jianghua; Shin, Hyun-Dong; Du, Guocheng; Liu, Long; Chen, Jian
2015-11-01
Organic acids, which are chemically synthesized, are also natural intermediates in the metabolic pathways of microorganisms, among which the tricarboxylic acid (TCA) cycle is the most crucial route existing in almost all living organisms. Organic acids in the TCA cycle include citric acid, α-ketoglutaric acid, succinic acid, fumaric acid, l-malic acid, and oxaloacetate, which are building-block chemicals with wide applications and huge markets. In this review, we summarize the synthesis pathways of these organic acids and review recent advances in metabolic engineering strategies that enhance organic acid production. We also propose further improvements for the production of organic acids with systems and synthetic biology-guided metabolic engineering strategies. Copyright © 2015 Elsevier Inc. All rights reserved.
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Akesson, B; Sundler, R; Nilsson, A
1976-03-16
Hepatocytes isolated from rat or pig by collagenase perfusion were incubated with [3H]glcyerol and different albumin-bount fatty acids. Among C22 fatty acids docosahexaenoic acid stimulated phosphatidylethanolamine synthesis in rat hepatocytes most effectively. Addition of docosahexaenoic acid plus either palmitic or stearic acid resulted almost in the same stimulation whereas combinations of this acid with lauric or myristic acid had no effect. Lauric acid and myristic acid alone inhibited phosphatidylethanolamine synthesis. The chain length specificity for monoenoic fatty acids was similar, the hexadecenoic and octadecenoic acids (both cis and trans) being most stimulatory. The addition of 0.2 mM ethanolamine markedly stimulated phosphatidylethanolamine synthesis, but most effects of fatty acids were similar in its presence or absence.
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Fautz, E; Rosenfelder, G; Grotjahn, L
1979-01-01
The fatty acids present in the total hydrolysates of several gliding bacteria (Myxococcus fulvus, Stigmatella aurantiaca, Cytophaga johnsonae, Cytophaga sp. strain samoa and Flexibacter elegans) were analyzed by combined gas-liquid chromatography and mass spectrometry. In addition to 13-methyl-tetradecanoic acid, 15-methyl-hexadecanoic acid, hexadecanoic acid, and hexadecenoic acid, 2- and 3-hydroxy fatty acids comprised up to 50% of the total fatty acids. The majority was odd-numbered and iso-branched. Small amounts of even-numbered and unbranched fatty acids were also present. Whereas 2-hydroxy-15-methyl hexadecanoic acid was characteristic for myxobacteria, 2-hydroxy-13-methyl-tetradecanoic acid, 3-hydroxy-13-methyl-tetradecanoic acid, and 3-hydroxy-15-methyl-hexadecanoic acid were dominant in the Cytophaga-Flexibacter group. PMID:118159
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Macrocyclic lactones: A versatile source for omega radiohalogenated fatty acid analogs
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dougan, A.H.; Lyster, D.M.; Robertson, K.A.
For each omega halogenated fatty acid there exists a potential omega hydroxy fatty acid and the corresponding macrocyclic lactone. The authors have utilized such lactones as starting materials for omega /sup 123/I fatty acid analogs intended for myocardial imaging. Macrocyclic musk lactones are industrially available; 120 analogs are described in the literature. The preparation requires saponification, tosylation, and radio-iodide substitution. Iodo-fatty acids are readily separated from tosylate fatty acids on TLC. While providing a secure source of 16-iodo-hexadecanoic acid and 17-iodo-heptadecanoic acid, the scheme allows ready access to a large number of untried fatty acid analogs. Examples presented are 16-iodo-hexadecanoicmore » acid, 16-iodo-7-hexadecanoic acid, 16-iodo-12-oxa-hexadecanoic acid, 15-iodo-pentadecanoic acid, and 15-iodo-12-keto-pentadecanoic acid. Metabolic studies are in progress in mice and dogs to assess the utility of these analogs for myocardial imaging.« less
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NASA Astrophysics Data System (ADS)
Somphon, Weenawan; Haller, Kenneth J.
2013-01-01
Pharmaceutical cocrystals are multicomponent materials containing an active pharmaceutical ingredient with another component in well-defined stoichiometry within the same unit cell. Such cocrystals are important in drug design, particularly for improving physicochemical properties such as solubility, bioavailability, or chemical stability. Picolinic acid is an endogenous metabolite of tryptophan and is widely used for neuroprotective, immunological, and anti-proliferative effects within the body. In this paper we present cocrystallization experiments of a series of dicarboxylic acids, oxalic acid, succinic acid, DL-tartaric acid, pimelic acid, and phthalic acid, with picolinic acid. Characterization by FT-IR and Raman spectroscopy, DSC and TG/DTG analysis, and X-ray powder diffraction show that new compounds are formed, including a 1:1 picolinium tartrate monohydrate, a 2:1 monohydrate adduct of picolinic acid and oxalic acid, and a 2:1 picolinic acid-succinic acid monohydrate cocrystal.
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Sato, Itaru; Kofujita, Hisayoshi; Tsuda, Shuji
2007-07-01
Japanese horse chestnut (Aesculus turbinata) seed extract inhibits the activity of cyclooxygenase (COX), but its active constituents have not been identified. In the present study, COX inhibitors were isolated from the hexane extract of this seed by means of 4 steps of liquid chromatography and were identified by gas chromatography/mass spectrometry and nuclear magnetic resonance. The COX inhibitors in the extract of Japanese horse chestnut seeds were identified as linoleic acid, linolenic acid, and oleic acid. Their efficacies were in the following order: linolenic acid = linoleic acid > oleic acid. These active constituents are C18 unsaturated fatty acids; stearic acid, a C18 saturated fatty acid, had no activity. Linolenic acid and linoleic acid had high selectivity toward COX-2 (selectivity index = 10), whereas oleic acid had no selectivity. Considering the efficacy and yield of each fatty acid, linoleic acid may be the principal COX inhibitor in this seed.
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Glutamic Acid as a Precursor to N-Terminal Pyroglutamic Acid in Mouse Plasmacytoma Protein
Twardzik, Daniel R.; Peterkofsky, Alan
1972-01-01
Cell suspensions derived from a mouse plasmacytoma (RPC-20) that secretes an immunoglobulin light chain containing N-terminal pyroglutamic acid can synthesize protein in vitro. Chromatographic examination of an enzymatic digest of protein labeled with glutamic acid shows only labeled glutamic acid and pyroglutamic acid; hydrolysis of protein from cells labeled with glutamine, however, yields substantial amounts of glutamic acid in addition to glutamine and pyroglutamic acid. The absence of glutamine synthetase and presence of glutaminase in plasmacytoma homogenates is consistent with these findings. These data indicate that N-terminal pyroglutamic acid can be derived from glutamic acid without prior conversion of glutamic acid to glutamine. Since free or bound forms of glutamine cyclize nonezymatically to pyroglutamate with ease, while glutamic acid does not, the data suggest that N-terminal pyroglutamic acid formation from glutamic acid is enzymatic rather than spontaneous. Images PMID:4400295
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Sakuradani, Eiji; Nojiri, Masutoshi; Suzuki, Haruna; Shimizu, Sakayu
2009-09-01
The isolation and characterization of a gene (MALCE1) that encodes a fatty acid elongase from arachidonic acid-producing fungus Mortierella alpina 1S-4 are described. MALCE1 was confirmed to encode a fatty acid elongase by its expression in yeast Saccharomyces cerevisiae, resulting in the accumulation of 18-, 19-, and 20-carbon monounsaturated fatty acids and eicosanoic acid. Furthermore, the MALCE1 yeast transformant efficiently elongated exogenous 9-hexadecenoic acid, 9,12-octadecadienoic acid, and 9,12,15-octadecatrienoic acid. The MALCE1 gene-silenced strain obtained from M. alpina 1S-4 exhibited a low content of octadecanoic acid and a high content of hexadecanoic acid, compared with those in the wild strain. The enzyme encoded by MALCE1 was demonstrated to be involved in the conversion of hexadecanoic acid to octadecanoic acid, its main role in M. alpina 1S-4.
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Fatty Acids of Myxococcus xanthus
Ware, Judith C.; Dworkin, Martin
1973-01-01
Fatty acids were extracted from saponified vegetative cells and myxospores of Myxococcus xanthus and examined as the methyl esters by gas-liquid chromatography. The acids consisted mainly of C14 to C17 species. Branched acids predominated, and iso-pentadecanoic acid constituted half or more of the mixture. The other leading component (11–28%) was found to be 11-n-hexadecenoic acid. Among the unsaturated acids were two diunsaturated ones, an n-hexadecadienoic acid and an iso-heptadecadienoic acid. No significant differences between the fatty acid compositions of the vegetative cells and myxospores could be detected. The fatty acid composition of M. xanthus was found to be markedly similar to that of Stigmatella aurantiaca. It is suggested that a fatty acid pattern consisting of a large proportion of iso-branched C15 and C17 acids and a substantial amount of an n-16:1 acid is characteristic of myxobacteria. PMID:4197903
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NASA Astrophysics Data System (ADS)
Cronin, J. R.; Pizzarello, S.; Epstein, S.; Krishnamurthy, R. V.
1993-10-01
The hydroxymonocarboxylic acids, dicarboxylic acids, and hydroxydicarboxylic acids of the Murchison meteorite were analyzed as their tert-butyldimethylsilyl derivatives using combined gas chromatography-mass spectrometry. The hydroxydicarboxylic acids have not been found previously in meteorites. Each class of compounds is numerous with carbon chains up to C8 or C9 and many, if not all, chain and substitution position isomers represented at each carbon number. The alpha-hydroxycarboxylic acids and alpha-hydroxydicarboxylic acids correspond structurally to many of the known meteoritic alpha-aminocarboxylic acids and alpha-aminodicarboxylic acids, a fact that supports the proposal that a Strecker synthesis was involved in the formation of both classes of compounds. Isotopic analyses show these acids to be D-rich relative to terrestrial organic compounds, as expected; however, the hydroxy acids appear to be isotopically lighter than the amino acids with respect to both carbon and hydrogen.
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Pang, Yuehan; Ahmed, Sulaiman; Xu, Yanjie; Beta, Trust; Zhu, Zhiwei; Shao, Yafang; Bao, Jinsong
2018-02-01
Total phenolic content (TPC), individual phenolic acid and antioxidant capacity of whole grain and bran fraction 18 rices with different bran color were investigated. The levels of TPC in bound fractions were significantly higher than those in the free fractions either in the whole grains or brans. The main bound phenolic acids in white rice samples were ferulic acid, p-coumaric acid, and isoferulic acid, and in pigmented rice samples were ferulic acid, p-coumaric acid, and vanillic acid. The protocatechuic acid and 2,5-dihydroxybenzoic acid were not detected in white samples. The content of gallic acid, protocatechuic acid, 2,5-dihydroxybenzoic acid, ferulic acid, sinapic acid had significantly positive correlations with TPC and antioxidant capacity. This study found much wider diversity in the phenolics and antioxidant capacity in the whole grain and brans of rice, and will provide new opportunities to further improvement of rice with enhanced levels of the phytochemicals. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Yin, Dengyang; Hu, Xunxiu; Liu, Dantong; Du, Wencheng; Wang, Haibo; Guo, Mengzhe; Tang, Daoquan
2017-06-01
Liquid chromatography coupled with mass spectrometry technique has been widely used in the analysis of biological targets such as amino acids, peptides, and proteins. In this work, eight common single carboxylic acids or diacids, which contain different pKa have been investigated as the additives to the analysis of amino acids. As the results, carboxylic acid additive can improve the signal intensity of acidity amino acids such as Asp and Glu and the chromatographic separation of basic amino acids such as Arg, His, and Lys. In particular, the diacids have better performance than single acids. The proposed mechanism is that the diacid has hydrogen bond interaction with amino acids to reduce their polarity/amphiprotic characteristics. Besides, oxalic acid has been found having better enhancement than phthalic acid by overall consideration. Therefore, we successfully quantified the 15 amino acids in Sepia bulk pharmaceutical chemical by using oxalic acid as the additive.
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Fatty Acid-Based Monomers as Styrene Replacements for Liquid Molding Resins
2005-05-01
fatty acid length and unsaturation level on resin and polymer properties. Fig. 2. The addition of fatty acids ( oleic acid ) to glycidyl methacylate to...the synthetic route used to form the methacrylated fatty acids (MFA). The carboxylic acid of fatty acids undergoes a simple addition reaction with... form methacrylated fatty acid monomer
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Acetic acid in aged vinegar affects molecular targets for thrombus disease management.
Jing, Li; Yanyan, Zhang; Junfeng, Fan
2015-08-01
To elucidate the mechanism underlying the action of dietary vinegar on antithrombotic activity, acetic acid, the main acidic component of dietary vinegar, was used to determine antiplatelet and fibrinolytic activity. The results revealed that acetic acid significantly inhibits adenosine diphosphate (ADP)-, collagen-, thrombin-, and arachidonic acid (AA)-induced platelet aggregation. Acetic acid (2.00 mM) reduced AA-induced platelet aggregation to approximately 36.82 ± 1.31%, and vinegar (0.12 mL L(-1)) reduced the platelet aggregation induced by AA to 30.25 ± 1.34%. Further studies revealed that acetic acid exerts its effects by inhibiting cyclooxygenase-1 and the formation of thromboxane-A2. Organic acids including acetic acid, formic acid, lactic acid, citric acid, and malic acid also showed fibrinolytic activity; specifically, the fibrinolytic activity of acetic acid amounted to 1.866 IU urokinase per mL. Acetic acid exerted its fibrinolytic activity by activating plasminogen during fibrin crossing, thus leading to crosslinked fibrin degradation by the activated plasmin. These results suggest that organic acids in dietary vinegar play important roles in the prevention and cure of cardiovascular diseases.
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Lucas, J.N.; Straume, T.; Bogen, K.T.
1998-03-24
A method is provided for detecting nucleic acid sequence aberrations using two immobilization steps. According to the method, a nucleic acid sequence aberration is detected by detecting nucleic acid sequences having both a first nucleic acid sequence type (e.g., from a first chromosome) and a second nucleic acid sequence type (e.g., from a second chromosome), the presence of the first and the second nucleic acid sequence type on the same nucleic acid sequence indicating the presence of a nucleic acid sequence aberration. In the method, immobilization of a first hybridization probe is used to isolate a first set of nucleic acids in the sample which contain the first nucleic acid sequence type. Immobilization of a second hybridization probe is then used to isolate a second set of nucleic acids from within the first set of nucleic acids which contain the second nucleic acid sequence type. The second set of nucleic acids are then detected, their presence indicating the presence of a nucleic acid sequence aberration. 14 figs.
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Lucas, Joe N.; Straume, Tore; Bogen, Kenneth T.
1998-01-01
A method is provided for detecting nucleic acid sequence aberrations using two immobilization steps. According to the method, a nucleic acid sequence aberration is detected by detecting nucleic acid sequences having both a first nucleic acid sequence type (e.g., from a first chromosome) and a second nucleic acid sequence type (e.g., from a second chromosome), the presence of the first and the second nucleic acid sequence type on the same nucleic acid sequence indicating the presence of a nucleic acid sequence aberration. In the method, immobilization of a first hybridization probe is used to isolate a first set of nucleic acids in the sample which contain the first nucleic acid sequence type. Immobilization of a second hybridization probe is then used to isolate a second set of nucleic acids from within the first set of nucleic acids which contain the second nucleic acid sequence type. The second set of nucleic acids are then detected, their presence indicating the presence of a nucleic acid sequence aberration.
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Bile Acid Metabolism in Liver Pathobiology
Chiang, John Y. L.; Ferrell, Jessica M.
2018-01-01
Bile acids facilitate intestinal nutrient absorption and biliary cholesterol secretion to maintain bile acid homeostasis, which is essential for protecting liver and other tissues and cells from cholesterol and bile acid toxicity. Bile acid metabolism is tightly regulated by bile acid synthesis in the liver and bile acid biotransformation in the intestine. Bile acids are endogenous ligands that activate a complex network of nuclear receptor farnesoid X receptor and membrane G protein-coupled bile acid receptor-1 to regulate hepatic lipid and glucose metabolic homeostasis and energy metabolism. The gut-to-liver axis plays a critical role in the regulation of enterohepatic circulation of bile acids, bile acid pool size, and bile acid composition. Bile acids control gut bacteria overgrowth, and gut bacteria metabolize bile acids to regulate host metabolism. Alteration of bile acid metabolism by high-fat diets, sleep disruption, alcohol, and drugs reshapes gut microbiome and causes dysbiosis, obesity, and metabolic disorders. Gender differences in bile acid metabolism, FXR signaling, and gut microbiota have been linked to higher prevalence of fatty liver disease and hepatocellular carcinoma in males. Alteration of bile acid homeostasis contributes to cholestatic liver diseases, inflammatory diseases in the digestive system, obesity, and diabetes. Bile acid-activated receptors are potential therapeutic targets for developing drugs to treat metabolic disorders. PMID:29325602
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Parabanic acid is the singlet oxygen specific oxidation product of uric acid.
Iida, Sayaka; Ohkubo, Yuki; Yamamoto, Yorihiro; Fujisawa, Akio
2017-11-01
Uric acid quenches singlet oxygen physically or reacts with it, but the oxidation product has not been previously characterized. The present study determined that the product is parabanic acid, which was confirmed by LC/TOFMS analysis. Parabanic acid was stable at acidic pH (<5.0), but hydrolyzed to oxaluric acid at neutral or alkaline pH. The total yields of parabanic acid and oxaluric acid based on consumed uric acid were ~100% in clean singlet oxygen production systems such as UVA irradiation of Rose Bengal and thermal decomposition of 3-(1,4-dihydro-1,4-epidioxy-4-methyl-1-naphthyl)propionic acid. However, the ratio of the amount of uric acid consumed to the total amount of singlet oxygen generated was less than 1/180, indicating that most of the singlet oxygen was physically quenched. The total yields of parabanic acid and oxaluric acid were high in the uric acid oxidation systems with hydrogen peroxide plus hypochlorite or peroxynitrite. They became less than a few percent in peroxyl radical-, hypochlorite- or peroxynitrite-induced oxidation of uric acid. These results suggest that parabanic acid could be an in vivo probe of singlet oxygen formation because of the wide distribution of uric acid in human tissues and extracellular spaces. In fact, sunlight exposure significantly increased human skin levels of parabanic acid.
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Hou, Yunyun; Liu, Xiaoyan; Zhang, Xinying; Chen, Xiao; Tao, Kaiyun; Chen, Xueping; Liang, Xia; He, Chiquan
2015-11-01
Root exudates (REs) of Scirpus triqueter were extracted from the rhizosphere soil in this study. The components in the REs were identified by GC-MS. Many organic acids, such as hexadecanoic acid, pentadecanoic acid, vanillic acid, octadecanoic acid, citric acid, succinic acid, glutaric acid, and so on, were found. Batch simulated experiments were conducted to evaluate the impacts of different organic acids, such as citric acid, artificial root exudates (ARE), succinic acid, and glutaric acid in REs of S. triqueter on desorption of pyrene (PYR) and lead (Pb) in co-contaminated wetland soils. The desorption amount of PYR and Pb increased with the rise in concentrations of organic acids in the range of 0-50 g·L(-1), within shaking time of 2-24 h. The desorption effects of PYR and Pb in soils with various organic acids treatments decreased in the following order: citric acid > ARE > succinic acid > glutaric acid. The desorption rate of PYR and Pb was higher in co-contaminated soil than in single pollution soil. The impacts of organic acids in REs of S. triqueter on bioavailability of PYR and Pb suggested that organic acids enhanced the bioavailability of PYR and Pb in wetland soil, and the bioavailability effects of organic acids generally followed the same order as that of desorption effects.
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Darwin; WipaCharles; Cord-Ruwisch, Ralf
2018-01-01
Organic acid analysis of fermentation samples can be readily achieved by gas chromatography (GC), which detects volatile organic acids. However, lactic acid, a key fermentation acid is non-volatile and can hence not be quantified by regular GC analysis. However the addition of periodic acid to organic acid samples has been shown to enable lactic acid analysis by GC, as periodic acid oxidizes lactic acid to the volatile acetaldehyde. Direct GC injection of lactic acid standards and periodic acid generated inconsistent and irreproducible peaks, possibly due to incomplete lactic acid oxidation to acetaldehyde. The described method is developed to improve lactic acid analysis by GC by using a heat treated derivatization pre-treatment, such that it becomes independent of the retention time and temperature selection of the GC injector. Samples containing lactic acid were amended by periodic acid and heated in a sealed test tube at 100°C for at least 45 min before injecting it to the GC. Reproducible and consistent peaks of acetaldehyde were obtained. Simultaneous determination of lactic acid, acetone, ethanol, butanol, volatile fatty acids could also be accomplished by applying this GC method, enabling precise and convenient organic acid analysis of biological samples such as anaerobic digestion and fermentation processes. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Behaviors of D- and L-lactic acids during the brewing process of sake (Japanese rice wine).
Kodama, Shuji; Yamamoto, Atsushi; Matsunaga, Akinobu; Matsui, Keizou; Nakagomi, Kazuya; Hayakawa, Kazuichi
2002-02-13
The amounts of D- and L-lactic acids during the brewing process of sake were determined by capillary electrophoresis using 2-hydroxypropyl-beta-cyclodextrin as a chiral selector. Because L-lactic acid, which prevents the growth of nonuseful microorganisms, is a raw material of sake, the ratio of L-lactic acid to total lactic acid is almost 1.0 at the initial stage of sake brewing. During brewing, the ratio decreased gradually and finally reached 0.39. Yeast (Saccharomyces cerevisiae) for sake brewing produced D-lactic acid, but not L-lactic acid in a culture medium. These results suggest that the decrease in the ratio of L-lactic acid to total lactic acid during sake brewing resulted in D-lactic acid production by yeast. The ratios in 18 brands of sake obtained commercially ranged from 0.23 to 0.78. The levels of D-lactic acid in sake (140-274 mg/L) were in a narrower range than those of L-lactic acid (61-461 mg/L). Although the D-lactic acid level in sake did not correspond to total lactic acid level, the L-lactic acid level correlated well with total lactic acid level (R(2) = 0.867). These results suggest that the ratio of L-lactic acid to total lactic acid in sake reflected the amount of L-lactic acid added at the initial stage of sake brewing.
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Fatty Acid Composition and Volatile Constituents of Protaetia brevitarsis Larvae.
Yeo, Hyelim; Youn, Kumju; Kim, Minji; Yun, Eun-Young; Hwang, Jae-Sam; Jeong, Woo-Sik; Jun, Mira
2013-06-01
A total of 48 different volatile oils were identified form P. brevitarsis larvae by gas chromatography/mass spectrometry (GC/MS). Acids (48.67%) were detected as the major group in P. brevitarsis larvae comprising the largest proportion of the volatile compounds, followed by esters (19.84%), hydrocarbons (18.90%), alcohols (8.37%), miscellaneous (1.71%), aldehydes (1.35%) and terpenes (1.16%). The major volatile constituents were 9-hexadecenoic acid (16.75%), 6-octadecenoic acid (14.88%) and n-hexadecanoic acid (11.06%). The composition of fatty acid was also determined by GC analysis and 16 fatty acids were identified. The predominant fatty acids were oleic acid (C18:1, 64.24%) followed by palmitic acid (C16:0, 15.89%), palmitoleic acid (C16:1, 10.43%) and linoleic acid (C18:2, 4.69%) constituting more than 95% of total fatty acids. The distinguished characteristic of the fatty acid profile of P. brevitarsis larvae was the high proportion of unsaturated fatty acid (80.54% of total fatty acids) versus saturated fatty acids (19.46% of total fatty acids). Furthermore, small but significant amounts of linoleic, linolenic and γ-linolenic acids bestow P. brevitarsis larvae with considerable nutritional value. The novel findings of the present study provide a scientific basis for the comprehensive utilization of the insect as a nutritionally promising food source and a possibility for more effective utilization.
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Fatty Acid Composition and Volatile Constituents of Protaetia brevitarsis Larvae
Yeo, Hyelim; Youn, Kumju; Kim, Minji; Yun, Eun-Young; Hwang, Jae-Sam; Jeong, Woo-Sik; Jun, Mira
2013-01-01
A total of 48 different volatile oils were identified form P. brevitarsis larvae by gas chromatography/mass spectrometry (GC/MS). Acids (48.67%) were detected as the major group in P. brevitarsis larvae comprising the largest proportion of the volatile compounds, followed by esters (19.84%), hydrocarbons (18.90%), alcohols (8.37%), miscellaneous (1.71%), aldehydes (1.35%) and terpenes (1.16%). The major volatile constituents were 9-hexadecenoic acid (16.75%), 6-octadecenoic acid (14.88%) and n-hexadecanoic acid (11.06%). The composition of fatty acid was also determined by GC analysis and 16 fatty acids were identified. The predominant fatty acids were oleic acid (C18:1, 64.24%) followed by palmitic acid (C16:0, 15.89%), palmitoleic acid (C16:1, 10.43%) and linoleic acid (C18:2, 4.69%) constituting more than 95% of total fatty acids. The distinguished characteristic of the fatty acid profile of P. brevitarsis larvae was the high proportion of unsaturated fatty acid (80.54% of total fatty acids) versus saturated fatty acids (19.46% of total fatty acids). Furthermore, small but significant amounts of linoleic, linolenic and γ-linolenic acids bestow P. brevitarsis larvae with considerable nutritional value. The novel findings of the present study provide a scientific basis for the comprehensive utilization of the insect as a nutritionally promising food source and a possibility for more effective utilization. PMID:24471125
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Jaiswal, Rakesh; Kuhnert, Nikolai
2011-01-01
Burdock (Arcticum lappa L.) roots are used in folk medicine and also as a vegetable in Asian countries especially Japan, Korea, and Thailand. We have used LC-MS(n) (n = 2-4) to detect and characterize in burdock roots 15 quantitatively minor fumaric, succinic, and malic acid-containing chlorogenic acids, 11 of them not previously reported in nature. These comprise 3-succinoyl-4,5-dicaffeoyl or 1-succinoyl-3,4-dicaffeoylquinic acid, 1,5-dicaffeoyl-3-succinoylquinic acid, 1,5-dicaffeoyl-4-succinoylquinic acid, and 3,4-dicaffeoyl-5-succinoylquinic acid (M(r) 616); 1,3-dicaffeoyl-5-fumaroylquinic acid and 1,5-dicaffeoyl-4-fumaroylquinic acid (M(r) 614); 1,5-dicaffeoyl-3-maloylquinic acid, 1,4-dicaffeoyl-3-maloylquinic acid, and 1,5-dicaffeoyl-4-maloylquinic acid (M(r) 632); 1,3,5-tricaffeoyl-4-succinoylquinic acid (M(r) 778); 1,5-dicaffeoyl-3,4-disuccinoylquinic acid (M(r) 716); 1,5-dicaffeoyl-3-fumaroyl-4-succinoylquinic acid and 1-fumaroyl-3,5-dicaffeoyl-4-succinoylquinic acid (M(r) 714); dicaffeoyl-dimaloylquinic acid (M(r) 748); and 1,5-dicaffeoyl-3-succinoyl-4-dimaloylquinic acid (M(r) 732). All the structures have been assigned on the basis of LC-MS(n) patterns of fragmentation, relative hydrophobicity, and analogy of fragmentation patterns if compared to caffeoylquinic acids.
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Xie, Shuyu; Zhu, Luyan; Dong, Zhao; Wang, Xiaofang; Wang, Yan; Li, Xihe; Zhou, WenZhong
2011-04-01
Enrofloxacin-loaded solid lipid nanoparticles (SLN) were prepared using fatty acids (tetradecanoic acid, palmitic acid, stearic acid) as lipid matrix by hot homogenization and ultrasonication method. The effect of fatty acids on the characteristics and pharmacokinetics of the SLN were investigated. The results showed that the encapsulation efficiency and loading capacity of nanoparticles varied with fatty acids in the order of stearic acid>palmitic acid>tetradecanoic acid. Furthermore, stearic acid-SLN had larger particle size, bigger polydispersity index (PDI) and higher zeta potential compared with the other two fatty acid formulated SLN. The SLN showed sustained releases in vitro and the released enrofloxacin had the same antibacterial activity as that of the native enrofloxacin. Although in vitro release exhibited similar patterns, within 24 h the releasing rates of the three formulations were significantly different (tetradecanoic acid-SLN>palmitic acid-SLN>stearic acid-SLN). Pharmacokinetic study after a single dose of intramuscular administration to mice demonstrated that tetradecanoic acid-SLN, palmitic acid-SLN, and stearic acid-SLN increased the bioavailability by 6.79, 3.56 and 2.39 folds, and extended the mean residence time (MRT) of the drug from 10.60 h to 180.36, 46.26 and 19.09 h, respectively. These results suggest that the enrofloxacin-fatty acid SLN are promising formulations for sustained release while fatty acids had significant influences on the characteristics and performances of the SLN. Copyright © 2010 Elsevier B.V. All rights reserved.
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Albishri, Hassan M.; Almaghrabi, Omar A.; Moussa, Tarek A. A.
2013-01-01
Background: The growth in the production of biodiesel, which is principally fatty acid methyl esters (FAME), has been phenomenal in the last ten years because of the general desire to cut down on the release of greenhouse gases into the atmosphere, and also as a result of the increasing cost of fossil fuels. Objective: Establish whether there is any relationship between two different species (watermelon and muskmelon) within the same family (Cucurbitaceae) on fatty acid compositions and enumerate the different fatty acids in the two species. Materials and Methods: Extraction of fatty acids from the two species and preparation the extract to gas chromatography/mass spectroscopy analysis to determine the fatty acids compositions qualitatively and quantitatively. Results: The analyzed plants (watermelon and muskmelon) contain five saturated fatty acids; tetrdecanoic acid, pentadecanoic acid, hexadecanoic acid, heptadecanoic acid and octadecanoic acid with different concentrations, while muskmelon contains an extra saturated fatty acid named eicosanoic acid. The watermelon plant contains five unsaturated fatty acids while muskmelon contains three only, the two plants share in two unsaturated fatty acids named 9-hexadecenoic acid and 9-octadecenoic acid, the muskmelon plant contains higher amounts of these two acids (2.04% and 10.12%, respectively) over watermelon plant (0.88% and 0.25%, respectively). Conclusion: The chemical analysis of watermelon and muskmelon revealed that they are similar in saturated fatty acids but differ in unsaturated fatty acids which may be a criterion of differentiation between the two plants. PMID:23661995
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Yu, Haining; Li, Ran; Huang, Haiyong; Yao, Ru; Shen, Shengrong
2018-01-01
Short-chain fatty acids (SCFA) such as acetic acid, propionic acid, and butyric acid are produced by fermentation by gut microbiota. In this paper, we investigate the effects of SCFA on 3T3-L1 cells and the underlying molecular mechanisms. The cells were treated with acetic acid, propionic acid, or butyric acid when cells were induced to differentiate into adipocytes. MTT assay was employed to detect the viability of 3T3-L1 cells. Oil Red O staining was used to visualize the lipid content in 3T3-L1 cells. A triglyceride assay kit was used to detect the triacylglycerol content in 3T3-L1 cells. qRT-PCR and Western blot were used to evaluate the expression of metabolic enzymes. MTT results showed that safe concentrations of acetic acid, propionic acid, and butyric acid were less than 6.4, 3.2, and 0.8 mM, respectively. Oil Red O staining and triacylglycerols detection results showed that treatment with acetic acid, propionic acid, and butyric acid accelerated the 3T3-L1 adipocyte differentiation. qRT-PCR and Western blot results showed that the expressions of lipoprotein lipase (LPL), adipocyte fatty acid binding protein 4 (FABP4), fatty acid transporter protein 4 (FATP4), and fatty acid synthase (FAS) were significantly increased by acetic acid, propionic acid, and butyric acid treatment during adipose differentiation (p < 0.05). In conclusion, SCFA promoted lipid accumulation by modulating the expression of enzymes of fatty acid metabolism. © 2018 AOCS.
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Al-Farsi, Mohamed; Alasalvar, Cesarettin; Morris, Anne; Baron, Mark; Shahidi, Fereidoon
2005-09-21
Fresh and sun-dried dates of three native varieties from Oman, namely, Fard, Khasab, and Khalas, were examined for their antioxidant activity and total contents of anthocyanins, carotenoids, and phenolics, as well as free and bound phenolic acids. All results are expressed as mean value +/- standard deviation (n = 3) on a fresh weight basis. Fresh date varieties were found to be a good source of antioxidants (11687-20604 micromol of Trolox equiv/g), total contents of anthocyanins (0.24-1.52 mg of cyanidin 3-glucoside equiv/100 g), carotenoids (1.31-3.03 mg/100 g), phenolics (134-280 mg of ferulic acid equiv/100 g), free phenolic acids (2.61-12.27 mg/100 g), and bound phenolic acids (6.84-30.25 mg/100 g). A significant (p < 0.05) amount of antioxidants and carotenoids was lost after sun-drying of dates, whereas the total content of phenolics and free and bound phenolic acids increased significantly (p < 0.05). Anthocyanins were detected only in fresh dates. Date varieties had different levels and patterns of phenolic acids. Four free phenolic acids (protocatechuic acid, vanillic acid, syringic acid, and ferulic acid) and nine bound phenolic acids (gallic acid, protocatechuic acid, p-hydroxybenzoic acid, vanillic acid, caffeic acid, syringic acid, p-coumaric acid, ferulic acid, and o-coumaric acid) were tentatively identified. Of the date varieties studied, Khalas, which is considered to be premium quality, had higher antioxidant activity, total carotenoids, and bound phenolic acids than other varieties. These results suggest that all date varieties serve as a good source of natural antioxidants and could potentially be considered as a functional food or functional food ingredient, although some of their antioxidant constituents are lost during sun-drying.
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Essential Fatty Acid Deficiency in 2015: The Impact of Novel Intravenous Lipid Emulsions.
Gramlich, Leah; Meddings, Liisa; Alberda, Cathy; Wichansawakun, Sanit; Robbins, Sarah; Driscoll, David; Bistrian, Bruce
2015-09-01
The fatty acids, linoleic acid (18:2ω-6) and α-linolenic acid (18:3ω-3), are essential to the human diet. When these essential fatty acids are not provided in sufficient quantities, essential fatty acid deficiency (EFAD) develops. This can be suggested clinically by abnormal liver function tests or biochemically by an elevated Mead acid and reduced linoleic acid and arachidonic acid level, which is manifested as an elevated triene/tetraene ratio of Mead acid/arachidonic acid. Clinical features of EFAD may present later. With the introduction of novel intravenous (IV) lipid emulsions in North America, the proportion of fatty acids provided, particularly the essential fatty acids, varies substantially. We describe a case series of 3 complicated obese patients who were administered parenteral nutrition (PN), primarily using ClinOleic 20%, an olive oil-based lipid emulsion with reduced amounts of the essential fatty acids, linoleic and α-linolenic, compared with more conventional soybean oil emulsions throughout their hospital admission. Essential fatty acid profiles were obtained for each of these patients to investigate EFAD as a potential cause of abnormal liver enzymes. Although the profiles revealed reduced linoleic acid and elevated Mead acid levels, this was not indicative of the development of essential fatty acid deficiency, as reflected in the more definitive measure of triene/tetraene ratio. Instead, although the serum fatty acid panel reflected the markedly lower but still adequate dietary linoleic acid content and greatly increased oleic acid content in the parenteral lipid emulsion, the triene/tetraene ratio remained well below the level, indicating EFAD in each of these patients. The availability and use of new IV lipid emulsions in PN should encourage the clinician to review lipid metabolism based on the quantity of fatty acids provided in specific parenteral lipid emulsions and the expected impact of these lipid emulsions (with quite different fatty acid composition) on measured fatty acid profiles. © 2015 American Society for Parenteral and Enteral Nutrition.
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Abe, Masayuki; Ito, Yoshihiko; Oyunzul, Luvsandorj; Oki-Fujino, Tomomi; Yamada, Shizuo
2009-04-01
Saw palmetto extract (SPE), used widely for the treatment of benign prostatic hyperplasia (BPH) has been shown to bind alpha(1)-adrenergic, muscarinic and 1,4-dihydropyridine (1,4-DHP) calcium channel antagonist receptors. Major constituents of SPE are lauric acid, oleic acid, myristic acid, palmitic acid and linoleic acid. The aim of this study was to investigate binding affinities of these fatty acids for pharmacologically relevant (alpha(1)-adrenergic, muscarinic and 1,4-DHP) receptors. The fatty acids inhibited specific [(3)H]prazosin binding in rat brain in a concentration-dependent manner with IC(50) values of 23.8 to 136 microg/ml, and specific (+)-[(3)H]PN 200-110 binding with IC(50) values of 24.5 to 79.5 microg/ml. Also, lauric acid, oleic acid, myristic acid and linoleic acid inhibited specific [(3)H]N-methylscopolamine ([(3)H]NMS) binding in rat brain with IC(50) values of 56.4 to 169 microg/ml. Palmitic acid had no effect on specific [(3)H]NMS binding. The affinity of oleic acid, myristic acid and linoleic acid for each receptor was greater than the affinity of SPE. Scatchard analysis revealed that oleic acid and lauric acid caused a significant decrease in the maximal number of binding sites (B(max)) for [(3)H]prazosin, [(3)H]NMS and (+)-[(3)H]PN 200-110. The results suggest that lauric acid and oleic acid bind noncompetitively to alpha(1)-adrenergic, muscarinic and 1,4-DHP calcium channel antagonist receptors. We developed a novel and convenient method of determining 5alpha-reductase activity using LC/MS. With this method, SPE was shown to inhibit 5alpha-reductase activity in rat liver with an IC(50) of 101 microg/ml. Similarly, all the fatty acids except palmitic acid inhibited 5alpha-reductase activity, with IC(50) values of 42.1 to 67.6 microg/ml. In conclusion, lauric acid, oleic acid, myristic acid, and linoleic acid, major constituents of SPE, exerted binding activities of alpha(1)-adrenergic, muscarinic and 1,4-DHP receptors and inhibited 5alpha-reductase activity.
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A bioactive triterpene from Lantana camara.
Barre, J T; Bowden, B F; Coll, J C; DeJesus, J; De La Fuente, V E; Janairo, G C; Ragasa, C Y
1997-05-01
Lantana camara afforded a novel triterpene 22 beta-acetoxylantic acid and the known triterpenes, lantic acid, 22 beta-dimethylacryloyloxylantonolic acid, a mixture of 22 beta-dimethylacryloyloxy lantanolic acid and 22 beta-angeloyloxylantanolic acid and lantanolic acid. 22 beta-Acetoxylantic acid showed antimicrobial activity against Staphylococcus aureus and Salmonella typhi. This compound and 22 beta-dimethylacryloyloxy lantanolic acid also showed antimutagenic activity.
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Hydroxycarboxylic acids and salts
Kiely, Donald E; Hash, Kirk R; Kramer-Presta, Kylie; Smith, Tyler N
2015-02-24
Compositions which inhibit corrosion and alter the physical properties of concrete (admixtures) are prepared from salt mixtures of hydroxycarboxylic acids, carboxylic acids, and nitric acid. The salt mixtures are prepared by neutralizing acid product mixtures from the oxidation of polyols using nitric acid and oxygen as the oxidizing agents. Nitric acid is removed from the hydroxycarboxylic acids by evaporation and diffusion dialysis.
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Metabolic engineering of the shikimate pathway
Juminaga, Darmawi; Keasling, Jay D.
2017-01-10
The present disclosure relates to engineered microorganisms that produce amino acids and amino acid intermediates. In particular, the disclosure relates to recombinant nucleic acids encoding operons that increase production of aromatic amino acids and the aromatic amino acid intermediate shikimate; microorganisms with increased production of aromatic amino acids and the aromatic amino acid intermediate shikimate; and methods related to the production of aromatic amino acids, the aromatic amino acid intermediate shikimate, and commodity chemicals derived therefrom.
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Fatty Acids Present in the Lipopolysaccharide of Rhizobium trifolii
Russa, R.; Lorkiewicz, Z.
1974-01-01
Approximately 70% of the fatty acids recovered after acid or alkaline hydrolysis of the lipopolysaccharide of Rhizobium trifolii were hydroxy fatty acids identified as hydroxymyristic and hydroxypalmitic acids. Palmitic acid was the only saturated fatty acid found in the lipopolysaccharide of R. trifolii. Octadecenoic and a small amount of hexadecenoic acids were also identified. The results of BF3 methanolysis and hydroxylaminolysis suggest that hydroxypalmitic acid is N-acyl bound. PMID:4852028
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Straight and branched-chain fatty acids in preorbital glands of sika deer, Cervus nippon.
Wood, William F
2004-02-01
Using GC-MS analysis, 11 major volatile compounds were found in the preorbital gland secretion from a female sika deer, Cervus nippon. These compounds are the C14 through C18 straight-chain fatty acids, (ZZ)-9,12-octadecadienoic acid, 12-methyltridecanoic acid, 13-methyltetradecanoic acid, 14-methylpentadecanoic acid, 14-methylhexadecanoic acid, and 15-methylhexadecanoic acid. The five branched-chain acids make up over 29% of the volatiles in the gland. This is the first time branched-chain carboxylic acids have been reported from ungulate preorbital glands.
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Catalá, A; Avanzati, B
1983-11-01
Oleic acid transfer from microsomes or mitochondria to egg lecithin liposomes was stimulated by fatty acid binding protein. By gel filtration, it could be demonstrated that this protein incorporates oleic acid into liposomes. Fatty acid binding protein transfer activity was higher using microsomes rather than mitochondria, which suggests a selective interaction with different kinds of membranes. Transfer of oleic acid by this soluble protein is greater than that of stearic acid. The results indicate that fatty acid binding protein may participate in the intracellular transport of fatty acids.
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Characterization of polar organics in airborne particulate matter
NASA Astrophysics Data System (ADS)
Yokouchi, Y.; Ambe, Y.
The methanol-extractable highly polar organics in atmospheric aerosol were characterized using GC-MS. Dicarboxylic acids having 2-16 carbon numbers were detected with a total concentration of 172 ng m -3. Azelaic acid ( C9) was the most abundant diacid and it possibly originated from the ozonolysis of unsaturated carboxylic acids such as oleic acid and linoleic acid, which mainly originate from terrestrial plants. A compound, which was tentatively identified as tetrahydrofuroic acid, contributed to about 10% of the highly polar organics. Other polyfunctional compounds found in the samples included some ketocarboxylic acids and aromatic acids such as phthalic acids, anisic acid and vanillic acid.
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Eto, Kei; Arimura, Yukiko; Mizuguchi, Hiroko; Nishikawa, Masazumi; Noda, Mami; Ishibashi, Hitoshi
2006-11-01
The effects of docosahexaenoic acid (DHA) and other fatty acids on P2X-receptor-mediated inward currents in rat nodose ganglion neurons were studied using the nystatin perforated patch-clamp technique. DHA accelerated the desensitization rate of the ATP-induced current. DHA showed use-dependent inhibition of the peak ATP-induced current. Other polyunsaturated fatty acids, such as arachidonic acid and eicosapentaenoic acid, displayed a similar use-dependent inhibition. The inhibitory effects of saturated fatty acids including palmitic acid and arachidic acid were weaker than those of polyunsaturated fatty acids. The results suggest that fatty acids may modulate the P2X receptor-mediated response when the channel is in the open-state.
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Fatty Acid Compositions of Six Wild Edible Mushroom Species
Günç Ergönül, Pelin; Akata, Ilgaz; Kalyoncu, Fatih; Ergönül, Bülent
2013-01-01
The fatty acids of six wild edible mushroom species (Boletus reticulatus, Flammulina velutipes var. velutipes, Lactarius salmonicolor, Pleurotus ostreatus, Polyporus squamosus, and Russula anthracina) collected from different regions from Anatolia were determined. The fatty acids were identified and quantified by gas chromatography and studied using fruit bodies. Fatty acid composition varied among species. The dominant fatty acid in fruit bodies of all mushrooms was cis-linoleic acid (18 : 2). Percentage of cis-linoleic acid in species varied from 22.39% to 65.29%. The other major fatty acids were, respectively, cis-oleic, palmitic, and stearic acids. Fatty acids analysis of the mushrooms showed that the unsaturated fatty acids were at higher concentrations than saturated fatty acids. PMID:23844377
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Protein and metabolic engineering for the production of organic acids.
Liu, Jingjing; Li, Jianghua; Shin, Hyun-Dong; Liu, Long; Du, Guocheng; Chen, Jian
2017-09-01
Organic acids are natural metabolites of living organisms. They have been widely applied in the food, pharmaceutical, and bio-based materials industries. In recent years, biotechnological routes to organic acids production from renewable raw materials have been regarded as very promising approaches. In this review, we provide an overview of current developments in the production of organic acids using protein and metabolic engineering strategies. The organic acids include propionic acid, pyruvate, itaconic acid, succinic acid, fumaric acid, malic acid and citric acid. We also expect that rapid developments in the fields of systems biology and synthetic biology will accelerate protein and metabolic engineering for microbial organic acid production in the future. Copyright © 2017. Published by Elsevier Ltd.
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Meier, Anna K.; Worch, Sebastian; Böer, Erik; Hartmann, Anja; Mascher, Martin; Marzec, Marek; Scholz, Uwe; Riechen, Jan; Baronian, Kim; Schauer, Frieder; Bode, Rüdiger; Kunze, Gotthard
2017-01-01
Tannins and hydroxylated aromatic acids, such as gallic acid (3,4,5-trihydroxybenzoic acid), are plant secondary metabolites which protect plants against herbivores and plant-associated microorganisms. Some microbes, such as the yeast Arxula adeninivorans are resistant to these antimicrobial substances and are able to use tannins and gallic acid as carbon sources. In this study, the Arxula gallic acid decarboxylase (Agdc1p) which degrades gallic acid to pyrogallol was characterized and its function in tannin catabolism analyzed. The enzyme has a higher affinity for gallic acid (Km −0.7 ± 0.2 mM, kcat −42.0 ± 8.2 s−1) than to protocatechuic acid (3,4-dihydroxybenzoic acid) (Km −3.2 ± 0.2 mM, kcat −44.0 ± 3.2 s−1). Other hydroxylated aromatic acids, such as 3-hydroxybenzoic acid, 4-hydroxybenzoic acid, 2,3-dihydroxybenzoic acid, 2,4-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid are not gallic acid decarboxylase substrates. A. adeninivorans G1212/YRC102-AYNI1-AGDC1, which expresses the AGDC1 gene under the control of the strong nitrate inducible AYNI1 promoter achieved a maximum gallic acid decarboxylase activity of 1064.4 U/l and 97.5 U/g of dry cell weight in yeast grown in minimal medium with nitrate as nitrogen source and glucose as carbon source. In the same medium, gallic acid decarboxylase activity was not detected for the control strain G1212/YRC102 with AGDC1 expression under the control of the endogenous promoter. Gene expression analysis showed that AGDC1 is induced by gallic acid and protocatechuic acid. In contrast to G1212/YRC102-AYNI1-AGDC1 and G1212/YRC102, A. adeninivorans G1234 [Δagdc1] is not able to grow on medium with gallic acid as carbon source but can grow in presence of protocatechuic acid. This confirms that Agdc1p plays an essential role in the tannic acid catabolism and could be useful in the production of catechol and cis,cis-muconic acid. However, the protocatechuic acid catabolism via Agdc1p to catechol seems to be not the only degradation pathway. PMID:28966611
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Meier, Anna K; Worch, Sebastian; Böer, Erik; Hartmann, Anja; Mascher, Martin; Marzec, Marek; Scholz, Uwe; Riechen, Jan; Baronian, Kim; Schauer, Frieder; Bode, Rüdiger; Kunze, Gotthard
2017-01-01
Tannins and hydroxylated aromatic acids, such as gallic acid (3,4,5-trihydroxybenzoic acid), are plant secondary metabolites which protect plants against herbivores and plant-associated microorganisms. Some microbes, such as the yeast Arxula adeninivorans are resistant to these antimicrobial substances and are able to use tannins and gallic acid as carbon sources. In this study, the Arxula gallic acid decarboxylase (Agdc1p) which degrades gallic acid to pyrogallol was characterized and its function in tannin catabolism analyzed. The enzyme has a higher affinity for gallic acid (K m -0.7 ± 0.2 mM, k cat -42.0 ± 8.2 s -1 ) than to protocatechuic acid (3,4-dihydroxybenzoic acid) (K m -3.2 ± 0.2 mM, k cat -44.0 ± 3.2 s -1 ). Other hydroxylated aromatic acids, such as 3-hydroxybenzoic acid, 4-hydroxybenzoic acid, 2,3-dihydroxybenzoic acid, 2,4-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid are not gallic acid decarboxylase substrates. A. adeninivorans G1212/YRC102-AYNI1-AGDC1, which expresses the AGDC1 gene under the control of the strong nitrate inducible AYNI1 promoter achieved a maximum gallic acid decarboxylase activity of 1064.4 U/l and 97.5 U/g of dry cell weight in yeast grown in minimal medium with nitrate as nitrogen source and glucose as carbon source. In the same medium, gallic acid decarboxylase activity was not detected for the control strain G1212/YRC102 with AGDC1 expression under the control of the endogenous promoter. Gene expression analysis showed that AGDC1 is induced by gallic acid and protocatechuic acid. In contrast to G1212/YRC102-AYNI1-AGDC1 and G1212/YRC102, A. adeninivorans G1234 [Δ agdc1 ] is not able to grow on medium with gallic acid as carbon source but can grow in presence of protocatechuic acid. This confirms that Agdc1p plays an essential role in the tannic acid catabolism and could be useful in the production of catechol and cis,cis -muconic acid. However, the protocatechuic acid catabolism via Agdc1p to catechol seems to be not the only degradation pathway.
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Amrutha, Balagopal; Sundar, Kothandapani; Shetty, Prathapkumar Halady
2017-10-01
Organic acids are known to be used as food preservatives due to their antimicrobial potential. This study evaluated the ability of three organic acids, namely, acetic acid, citric acid and lactic acid to manage E. coli and Salmonella sp. from fresh fruits and vegetables. Effect of these organic acids on biofilm forming ability and anti-quorum potential was also investigated. The effect of organic acids on inactivation of E. coli and Salmonella sp. on the surface of a selected vegetable (cucumber) was determined. The minimum inhibitory concentration of the organic acids were found to be 1.5, 2 and 0.2% in E. coli while it was observed to be 1, 1.5 and 1% in Salmonella sp. for acetic, citric and lactic acids respectively. Maximum inhibition of biofilm formation was recorded at 39.13% with lactic acid in E. coli and a minimum of 22.53% with citric acid in Salmonella sp. EPS production was affected in E. coli with lactic acid showing reduction by 13.42% while citric acid and acetic acid exhibited only 6.25% and 10.89% respectively. Swimming and swarming patterns in E. coli was notably affected by both acetic and lactic acids. Lactic and acetic acids showed higher anti-quorum sensing (QS) potential when compared to citric acid. 2% lactic acid showed a maximum inhibition of violacein production by 37.7%. Organic acids can therefore be used as potential quorum quenching agents in food industry. 2% lactic acid treatment on cucumber demonstrated that it was effective in inactivating E. coli and Salmonella sp. There was 1 log reduction in microbial count over a period of 6 days after the lactic acid treatment. Thus, organic acids can act as effective potential sanitizers in reducing the microbial load associated with fresh fruits and vegetables. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Yokoyama, Yukihiro; Mizuno, Takashi; Sugawara, Gen; Asahara, Takashi; Nomoto, Koji; Igami, Tsuyoshi; Ebata, Tomoki; Nagino, Masato
2017-10-01
To investigate the association between preoperative fecal organic acid concentrations and the incidence of postoperative infectious complications in patients undergoing major hepatectomy with extrahepatic bile duct resection for biliary malignancies. The fecal samples of 44 patients were collected before undergoing hepatectomy with bile duct resection for biliary malignancies. The concentrations of fecal organic acids, including acetic acid, butyric acid, and lactic acid, and representative fecal bacteria were measured. The perioperative clinical characteristics and the concentrations of fecal organic acids were compared between patients with and without postoperative infectious complications. Among 44 patients, 13 (30%) developed postoperative infectious complications. Patient age and intraoperative bleeding were significantly greater in patients with postoperative infectious complications compared with those without postoperative infectious complications. The concentrations of fecal acetic acid and butyric acid were significantly less, whereas the concentration of fecal lactic acid tended to be greater in the patients with postoperative infectious complications. The calculated gap between the concentrations of fecal acetic acid plus butyric acid minus lactic acid gap was less in the patients with postoperative infectious complications (median 43.5 vs 76.1 μmol/g of feces, P = .011). Multivariate analysis revealed that an acetic acid plus butyric acid minus lactic acid gap <60 μmol/g was an independent risk factor for postoperative infectious complications with an odds ratio of 15.6; 95% confidence interval 1.8-384.1. The preoperative fecal organic acid profile (especially low acetic acid, low butyric acid, and high lactic acid) had a clinically important impact on the incidence of postoperative infectious complications in patients undergoing major hepatectomy with extrahepatic bile duct resection. Copyright © 2017. Published by Elsevier Inc.
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[Percentage of uric acid calculus and its metabolic character in Dongjiang River valley].
Chong, Hong-Heng; An, Geng
2009-02-15
To study the percentage of uric acid calculus in uroliths and its metabolic character in Dongjiang River valley. To analyze the chemical composition of 290 urinary stones by infrared (IR) spectroscopy and study the ratio changes of uric acid calculus. Uric acid calculus patients and healthy people were studied. Personal characteristics, dietary habits were collected. Conditional logistic regression was used for data analysis and studied the dietary risk factors of uric acid calculus. Patients with uric acid calculus, calcium oxalate and those without urinary calculus were undergone metabolic evaluation analysis. The results of uric acid calculus patients compared to another two groups to analysis the relations between the formation of uric acid calculus and metabolism factors. Uric acid calculi were found in 53 cases (18.3%). The multiple logistic regression analysis suggested that low daily water intake, eating more salted and animal food, less vegetable were very closely associated with uric acid calculus. Comparing to calcium oxalate patients, the urine volume, the value of pH, urine calcium, urine oxalic acid were lower, but uric acid was higher than it. The value of pH, urine oxalic acid and citric acid were lower than them, but uric acid and urine calcium were higher than none urinary calculus peoples. Blood potassium and magnesium were lower than them. The percentage of uric acid stones had obvious advanced. Less daily water intake, eating salted food, eating more animal food, less vegetables and daily orange juice intake, eating sea food are the mainly dietary risk factors to the formation of uric acid calculus. Urine volume, the value of pH, citric acid, urine calcium, urine uric acid and the blood natrium, potassium, magnesium, calcium, uric acid have significant influence to the information of uric acid stones.
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NASA Astrophysics Data System (ADS)
Müller-Tautges, C.; Eichler, A.; Schwikowski, M.; Pezzatti, G. B.; Conedera, M.; Hoffmann, T.
2016-01-01
Historic records of α-dicarbonyls (glyoxal, methylglyoxal), carboxylic acids (C6-C12 dicarboxylic acids, pinic acid, p-hydroxybenzoic acid, phthalic acid, 4-methylphthalic acid), and ions (oxalate, formate, calcium) were determined with annual resolution in an ice core from Grenzgletscher in the southern Swiss Alps, covering the time period from 1942 to 1993. Chemical analysis of the organic compounds was conducted using ultra-high-performance liquid chromatography (UHPLC) coupled to electrospray ionization high-resolution mass spectrometry (ESI-HRMS) for dicarbonyls and long-chain carboxylic acids and ion chromatography for short-chain carboxylates. Long-term records of the carboxylic acids and dicarbonyls, as well as their source apportionment, are reported for western Europe. This is the first study comprising long-term trends of dicarbonyls and long-chain dicarboxylic acids (C6-C12) in Alpine precipitation. Source assignment of the organic species present in the ice core was performed using principal component analysis. Our results suggest biomass burning, anthropogenic emissions, and transport of mineral dust to be the main parameters influencing the concentration of organic compounds. Ice core records of several highly correlated compounds (e.g., p-hydroxybenzoic acid, pinic acid, pimelic, and suberic acids) can be related to the forest fire history in southern Switzerland. P-hydroxybenzoic acid was found to be the best organic fire tracer in the study area, revealing the highest correlation with the burned area from fires. Historical records of methylglyoxal, phthalic acid, and dicarboxylic acids adipic acid, sebacic acid, and dodecanedioic acid are comparable with that of anthropogenic emissions of volatile organic compounds (VOCs). The small organic acids, oxalic acid and formic acid, are both highly correlated with calcium, suggesting their records to be affected by changing mineral dust transport to the drilling site.
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Nocturnal weakly acidic reflux promotes aspiration of bile acids in lung transplant recipients.
Blondeau, Kathleen; Mertens, Veerle; Vanaudenaerde, Bart A; Verleden, Geert M; Van Raemdonck, Dirk E; Sifrim, Daniel; Dupont, Lieven J
2009-02-01
Gastroesophageal reflux (GER) and aspiration of bile acids have been implicated as non-alloimmune risk factors for the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. The aim of our study was to investigate the association between GER and gastric aspiration of bile acids and to establish which reflux characteristics may promote aspiration of bile acids into the lungs and may feature as a potential diagnostic tool in identifying lung transplantation (LTx) patients at risk for aspiration. Twenty-four stable LTx recipients were studied 1 year after transplantation. All patients underwent 24-hour ambulatory impedance-pH recording for the detection of acid (pH <4) and weakly acidic (pH 4 to 7) reflux. On the same day, bronchoalveolar lavage fluid (BALF) was collected and then analyzed for the presence of bile acids (Bioquant enzymatic assay). Increased GER was detected in 13 patients, of whom 9 had increased acid reflux and 4 had exclusively increased weakly acidic reflux. Sixteen patients had detectable bile acids in the BALF (0.6 [0.4 to 1.5] micromol/liter). The 24-hour esophageal volume exposure was significantly increased in patients with bile acids compared to patients without bile acids in the BALF. Acid exposure and the number of reflux events (total, acid and weakly acidic) were unrelated to the presence of bile acids in the BALF. However, both nocturnal volume exposure and the number of nocturnal weakly acidic reflux events were significantly higher in patients with bile acids in the BALF. Weakly acidic reflux events, especially during the night, are associated with the aspiration of bile acids in LTx recipients and may therefore feature as a potential risk factor for the development of BOS.
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Ma, Dongyun; Li, Yaoguang; Zhang, Jian; Wang, Chenyang; Qin, Haixia; Ding, Huina; Xie, Yingxin; Guo, Tiancai
2016-01-01
Polyphenols in whole grain wheat have potential health benefits, but little is known about the expression patterns of phenolic acid biosynthesis genes and the accumulation of phenolic acid compounds in different-colored wheat grains. We found that purple wheat varieties had the highest total phenolic content (TPC) and antioxidant activity. Among phenolic acid compounds, bound ferulic acid, vanillic, and caffeic acid levels were significantly higher in purple wheat than in white and red wheat, while total soluble phenolic acid, soluble ferulic acid, and vanillic acid levels were significantly higher in purple and red wheat than in white wheat. Ferulic acid and syringic acid levels peaked at 14 days after anthesis (DAA), whereas p-coumaric acid and caffeic acid levels peaked at 7 DAA, and vanillic acid levels gradually increased during grain filling and peaked near ripeness (35 DAA). Nine phenolic acid biosynthesis pathway genes (TaPAL1, TaPAL2, TaC3H1, TaC3H2, TaC4H, Ta4CL1, Ta4CL2, TaCOMT1, and TaCOMT2) exhibited three distinct expression patterns during grain filling, which may be related to the different phenolic acids levels. White wheat had higher phenolic acid contents and relatively high gene expression at the early stage, while purple wheat had the highest phenolic acid contents and gene expression levels at later stages. These results suggest that the expression of phenolic acid biosynthesis genes may be closely related to phenolic acids accumulation.
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Ma, Dongyun; Li, Yaoguang; Zhang, Jian; Wang, Chenyang; Qin, Haixia; Ding, Huina; Xie, Yingxin; Guo, Tiancai
2016-01-01
Polyphenols in whole grain wheat have potential health benefits, but little is known about the expression patterns of phenolic acid biosynthesis genes and the accumulation of phenolic acid compounds in different-colored wheat grains. We found that purple wheat varieties had the highest total phenolic content (TPC) and antioxidant activity. Among phenolic acid compounds, bound ferulic acid, vanillic, and caffeic acid levels were significantly higher in purple wheat than in white and red wheat, while total soluble phenolic acid, soluble ferulic acid, and vanillic acid levels were significantly higher in purple and red wheat than in white wheat. Ferulic acid and syringic acid levels peaked at 14 days after anthesis (DAA), whereas p-coumaric acid and caffeic acid levels peaked at 7 DAA, and vanillic acid levels gradually increased during grain filling and peaked near ripeness (35 DAA). Nine phenolic acid biosynthesis pathway genes (TaPAL1, TaPAL2, TaC3H1, TaC3H2, TaC4H, Ta4CL1, Ta4CL2, TaCOMT1, and TaCOMT2) exhibited three distinct expression patterns during grain filling, which may be related to the different phenolic acids levels. White wheat had higher phenolic acid contents and relatively high gene expression at the early stage, while purple wheat had the highest phenolic acid contents and gene expression levels at later stages. These results suggest that the expression of phenolic acid biosynthesis genes may be closely related to phenolic acids accumulation. PMID:27148345
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Amino acid homeostasis and signalling in mammalian cells and organisms
Bröer, Angelika
2017-01-01
Cells have a constant turnover of proteins that recycle most amino acids over time. Net loss is mainly due to amino acid oxidation. Homeostasis is achieved through exchange of essential amino acids with non-essential amino acids and the transfer of amino groups from oxidised amino acids to amino acid biosynthesis. This homeostatic condition is maintained through an active mTORC1 complex. Under amino acid depletion, mTORC1 is inactivated. This increases the breakdown of cellular proteins through autophagy and reduces protein biosynthesis. The general control non-derepressable 2/ATF4 pathway may be activated in addition, resulting in transcription of genes involved in amino acid transport and biosynthesis of non-essential amino acids. Metabolism is autoregulated to minimise oxidation of amino acids. Systemic amino acid levels are also tightly regulated. Food intake briefly increases plasma amino acid levels, which stimulates insulin release and mTOR-dependent protein synthesis in muscle. Excess amino acids are oxidised, resulting in increased urea production. Short-term fasting does not result in depletion of plasma amino acids due to reduced protein synthesis and the onset of autophagy. Owing to the fact that half of all amino acids are essential, reduction in protein synthesis and amino acid oxidation are the only two measures to reduce amino acid demand. Long-term malnutrition causes depletion of plasma amino acids. The CNS appears to generate a protein-specific response upon amino acid depletion, resulting in avoidance of an inadequate diet. High protein levels, in contrast, contribute together with other nutrients to a reduction in food intake. PMID:28546457
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Differential Effects of Methoxylated p-Coumaric Acids on Melanoma in B16/F10 Cells
Yoon, Hoon Seok; Lee, Nam-Ho; Hyun, Chang-Gu; Shin, Dong-Bum
2015-01-01
As an approach to search for chemopreventive agents, we tested p-coumaric acid, 3-methoxy-p-coumaric acid (ferulic acid), and 3,5-dimethoxy-p-coumaric acid (sinapic acid) in B16/F10 melanoma cells. Intracellular melanin contents were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and cytotoxicity of the compounds were examined by lactate dehydrogenase (LDH) release. p-Coumaric acid showed inhibitory effect on melanogenesis, but ferulic acid increased melanin content, and sinapic acid had almost no effect on melanogenesis. Treatment with ferulic acid resulted in a 2 to 3 fold elevation in the production of melanin. Correlatively, cell viability decreased in a dose-dependent manner when treated with ferulic acid. However, ferulic acid did not affect the LDH release from the cells. Treatment with sinapic acid resulted in a 50~60% elevation in the release of LDH when treated with a 200 μg/mL concentration and showed neither cytostasis nor increase of melanin synthesis in a dose-dependent manner. Taken together, p-coumaric acid inhibits melanogenesis, ferulic acid induces melanogenesis, and sinapic acid exerts cytotoxic effects in B16/F10 murine melanoma cells. The results indicate that the addition of methoxy groups to p-coumaric acid shows the melanogenic or cytotoxic effects in melanoma cells compared to the original compound. Therefore, this study suggests the possibility that methoxylated p-coumaric acid, ferulic acid can be used as a chemopreventive agent. PMID:25866753
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Trans-Fats Inhibit Autophagy Induced by Saturated Fatty Acids.
Sauvat, Allan; Chen, Guo; Müller, Kevin; Tong, Mingming; Aprahamian, Fanny; Durand, Sylvère; Cerrato, Giulia; Bezu, Lucillia; Leduc, Marion; Franz, Joakim; Rockenfeller, Patrick; Sadoshima, Junichi; Madeo, Frank; Kepp, Oliver; Kroemer, Guido
2018-04-01
Depending on the length of their carbon backbone and their saturation status, natural fatty acids have rather distinct biological effects. Thus, longevity of model organisms is increased by extra supply of the most abundant natural cis-unsaturated fatty acid, oleic acid, but not by that of the most abundant saturated fatty acid, palmitic acid. Here, we systematically compared the capacity of different saturated, cis-unsaturated and alien (industrial or ruminant) trans-unsaturated fatty acids to provoke cellular stress in vitro, on cultured human cells expressing a battery of distinct biosensors that detect signs of autophagy, Golgi stress and the unfolded protein response. In contrast to cis-unsaturated fatty acids, trans-unsaturated fatty acids failed to stimulate signs of autophagy including the formation of GFP-LC3B-positive puncta, production of phosphatidylinositol-3-phosphate, and activation of the transcription factor TFEB. When combined effects were assessed, several trans-unsaturated fatty acids including elaidic acid (the trans-isomer of oleate), linoelaidic acid, trans-vaccenic acid and palmitelaidic acid, were highly efficient in suppressing autophagy and endoplasmic reticulum stress induced by palmitic, but not by oleic acid. Elaidic acid also inhibited autophagy induction by palmitic acid in vivo, in mouse livers and hearts. We conclude that the well-established, though mechanistically enigmatic toxicity of trans-unsaturated fatty acids may reside in their capacity to abolish cytoprotective stress responses induced by saturated fatty acids. Copyright © 2018 German Center for Neurodegenerative Diseases (DZNE). Published by Elsevier B.V. All rights reserved.
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Aydin, Cevat; Ozcan, Mehmet Musa; Gümüş, Tuncay
2009-08-01
Olea europea L. fruits were evaluated for weight, moisture, ash, crude protein, crude oil, energy, crude fibre, roundness, resistance against extra force and product density. The relative density, refractive index, free fatty acids, peroxide value, iodine value and unsaponifiables were determined in the olive oils. The main fatty acids identified by gas chromatography were palmitic acid (16:0), palmitoleic acid (16:1), stearic acid (18:0), oleic acid (18:1) and linoleic acid (18:2). Of the identified fatty acids, lauric acid (12:0), linolenic acid (18:3), arachidic acid (20:0), eicosenoic acid (20:1), behenic acid (22:0) and lignoseric acid (24:0) were found in trace amounts. As expected, the oleic acid content was the major fatty acid of olive oil. Oleic acid was represented in much higher concentrations than the other acids. The product roundness, resistance against extra force, product density and weight of 100 fruit were established as technological characteristics in olive fruit. The damage energy and the unit of volume deformation energy of the Memecik and Tavşanyüreği varieties were 1.36×10(-3) J and 3.59×10(-4) J/mm(3) and 1.89×10(-3) J and 5.10×10(-4) J/mm(3), respectively. The fruits showed a similar composition, and both fruit and oil contained unsaturated fatty acids.
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[Ganoderma triterpenoids from aqueous extract of Ganoderma lucidum].
Che, Xian-Qiang; Li, Shao-Ping; Zhao, Jing
2017-05-01
A new triterpenoid and 18 analogues were isolated from the water extract of Ganoderma lucidum by column chromatographic techniques, including silica gel, ODS, Sephadex LH-20, and HPLC. The new compound was elucidated as 2β-acetoxy-3β,25-dihydroxy-7,11,15-trioxo-lanost-8-en-26-oic acid on the basis of analyses of extensive spectroscopic data and its physicochemical properties. Comparison of NMR data with those reported in literature, the known analogues were determined as ganoderic acid H (2), 12β-acetoxy-3β,7β-dihydroxy-11,15,23-trioxo-lanost-8,16-dien-26-oic acid (3), ganoderenic acid D (4),ganoderic acid C1 (5),ganoderic acid G (6),3β,7β-dihydroxy-11,15,23-trioxo-lanost-8,16-dien-26-oic acid (7),ganoderic acid B (8),ganoderic acid C6 (9),3β,15α-dihydroxy-7,11,23-trioxo-lanost-8,16-dien-26-oic acid (10),ganoderic acid A (11),ganolucidic acid A (12),lucidenic acid E2 (13),lucidenic acid N (14),lucidenic acid P (15), lucidenic acid B (16),lucidenic acid A (17),lucidenic acid C (18),and lucidenic acid L (19), respectively. Compound 1 is new compound and compounds 2-19 have been reported from G. lucidum. The present study enriches the knowledge of the chemical constituent of G. lucidum and completes chemical investigation of water decoction that is traditional use of G. lucidum. Copyright© by the Chinese Pharmaceutical Association.
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Cooper, George; Reed, Chris; Nguyen, Dang; Carter, Malika; Wang, Yi
2011-01-01
Carbonaceous meteorites deliver a variety of organic compounds to Earth that may have played a role in the origin and/or evolution of biochemical pathways. Some apparently ancient and critical metabolic processes require several compounds, some of which are relatively labile such as keto acids. Therefore, a prebiotic setting for any such individual process would have required either a continuous distant source for the entire suite of intact precursor molecules and/or an energetic and compact local synthesis, particularly of the more fragile members. To date, compounds such as pyruvic acid, oxaloacetic acid, citric acid, isocitric acid, and α-ketoglutaric acid (all members of the citric acid cycle) have not been identified in extraterrestrial sources or, as a group, as part of a “one pot” suite of compounds synthesized under plausibly prebiotic conditions. We have identified these compounds and others in carbonaceous meteorites and/or as low temperature (laboratory) reaction products of pyruvic acid. In meteorites, we observe many as part of three newly reported classes of compounds: keto acids (pyruvic acid and homologs), hydroxy tricarboxylic acids (citric acid and homologs), and tricarboxylic acids. Laboratory syntheses using 13C-labeled reactants demonstrate that one compound alone, pyruvic acid, can produce several (nonenzymatic) members of the citric acid cycle including oxaloacetic acid. The isotopic composition of some of the meteoritic keto acids points to interstellar or presolar origins, indicating that such compounds might also exist in other planetary systems. PMID:21825143
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Young, R F; Orr, E A; Goss, G G; Fedorak, P M
2007-06-01
Naphthenic acids are a complex mixture of carboxylic acids that occur naturally in petroleum. During the extraction of bitumen from the oil sands in northeastern Alberta, Canada, naphthenic acids are released into the aqueous phase and these acids become the most toxic components in the process-affected water. Although previous studies have exposed fish to naphthenic acids or oil sands process-affected waters, there has been no analytical method to specifically detect naphthenic acids in fish. Here, we describe a qualitative method to specifically detect these acids. In 96-h static renewal tests, rainbow trout (Oncorhynchus mykiss) fingerlings were exposed to three different treatments: (1) fed pellets that contained commercial naphthenic acids (1.5mg g(-1) of food), (2) kept in tap water that contained commercial naphthenic acids (3mg l(-1)) and (3) kept in an oil sands process-affected water that contained 15mg naphthenic acids l(-1). Five-gram samples of fish were homogenized and extracted, then the mixture of free fatty acids and naphthenic acids was isolated from the extract using strong anion exchange chromatography. The mixture was derivatized and analyzed by gas chromatography-mass spectrometry. Reconstructed ion chromatograms (m/z=267) selectively detected naphthenic acids. These acids were present in each fish that was exposed to naphthenic acids, but absent in fish that were not exposed to naphthenic acids. The minimum detectable concentration was about 1microg naphthenic acids g(-1) of fish.
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Cooper, George; Reed, Chris; Nguyen, Dang; Carter, Malika; Wang, Yi
2011-08-23
Carbonaceous meteorites deliver a variety of organic compounds to Earth that may have played a role in the origin and/or evolution of biochemical pathways. Some apparently ancient and critical metabolic processes require several compounds, some of which are relatively labile such as keto acids. Therefore, a prebiotic setting for any such individual process would have required either a continuous distant source for the entire suite of intact precursor molecules and/or an energetic and compact local synthesis, particularly of the more fragile members. To date, compounds such as pyruvic acid, oxaloacetic acid, citric acid, isocitric acid, and α-ketoglutaric acid (all members of the citric acid cycle) have not been identified in extraterrestrial sources or, as a group, as part of a "one pot" suite of compounds synthesized under plausibly prebiotic conditions. We have identified these compounds and others in carbonaceous meteorites and/or as low temperature (laboratory) reaction products of pyruvic acid. In meteorites, we observe many as part of three newly reported classes of compounds: keto acids (pyruvic acid and homologs), hydroxy tricarboxylic acids (citric acid and homologs), and tricarboxylic acids. Laboratory syntheses using (13)C-labeled reactants demonstrate that one compound alone, pyruvic acid, can produce several (nonenzymatic) members of the citric acid cycle including oxaloacetic acid. The isotopic composition of some of the meteoritic keto acids points to interstellar or presolar origins, indicating that such compounds might also exist in other planetary systems.
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Chemical evolution. XXI - The amino acids released on hydrolysis of HCN oligomers
NASA Technical Reports Server (NTRS)
Ferris, J. P.; Wos, J. D.; Nooner, D. W.; Oro, J.
1974-01-01
Major amino acids released by hydrolysis of acidic and basic HCN oligomers are identified by chromatography as Gly, Asp, and diaminosuccinic acid. Smaller amounts of Ala, Ile and alpha-aminoisobutyric acid are also detected. The amino acids released did not change appreciably when the hydrolysis medium was changed from neutral to acidic or basic. The presence of both meso and d, l-diaminosuccinic acids was established by paper chromatography and on an amino acid analyzer.
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Manipulating Membrane Fatty Acid Compositions of Whole Plants with Tween-Fatty Acid Esters 1
Terzaghi, William B.
1989-01-01
This paper describes a method for manipulating plant membrane fatty acid compositions without altering growth temperature or other conditions. Tween-fatty acid esters carrying specific fatty acids were synthesized and applied to various organs of plants growing axenically in glass jars. Treated plants incorporated large amounts of exogenous fatty acids into all acylated membrane lipids detected. Fatty acids were taken up by both roots and leaves. Fatty acids applied to roots were found in leaves, while fatty acids applied to leaves appeared in both leaves higher on the plant and in roots, indicating translocation (probably in the phloem). Foliar application was most effective; up to 20% of membrane fatty acids of leaves above the treated leaf and up to 40% of root membrane fatty acids were exogenously derived. Plants which took up exogenous fatty acids changed their patterns of fatty acid synthesis such that ratios of saturated to unsaturated fatty acids remained essentially unaltered. Fatty acid uptake was most extensively studied in soybean (Glycine max [L.] Merr.), but was also observed in other species, including maize (Zea mays L.), mung beans (Vigna radiata L.), peas (Pisum sativum L.), petunia (Petunia hybrida L.) and tomato (Lycopersicon esculentum Mill.). Potential applications of this system include studying internal transport of fatty acids, regulation of fatty acid and membrane synthesis, and influences of membrane fatty acid composition on plant physiology. Images Figure 2 PMID:16666997
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NASA Astrophysics Data System (ADS)
Abbatt, J. P. D.; Broekhuizen, K.; Pradeep Kumar, P.
The ability of mixed ammonium sulfate/organic acid particles to act as cloud condensation nuclei (CCN) has been studied in the laboratory using a continuous flow, thermal-gradient diffusion chamber operated at supersaturations between 0.3% and 0.6%. The organic acids studied were malonic acid, azelaic acid, hexanoic acid, cis-pinonic acid, oleic acid and stearic acid, and the particles were largely prepared by condensation of the organic vapor onto a dry ammonium sulfate core. For malonic acid and hexanoic acid, the mixed particles activated as predicted by a simple Köhler theory model where both species are assumed to be fully soluble and the droplet has the surface tension of water. Three low-solubility species, cis-pinonic acid, azelaic acid and oleic acid, are well modeled where the acid was assumed to be either partially or fully insoluble. Interestingly, although thin coats of stearic acid behaved in a manner similar to that displayed by oleic and cis-pinonic acid, we observed that thick coats led to a complete deactivation of the ammonium sulfate, presumably because the water vapor could not diffuse through the solid stearic acid. We observed no CCN behavior that could be clearly attributed to a lowering of the surface tension of the growing droplet by the presence of the organic constituents, some of which are highly surface active.
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13-cis retinoic acid and isomerisation in paediatric oncology--is changing shape the key to success?
Armstrong, Jane L; Redfern, Christopher P F; Veal, Gareth J
2005-05-01
Retinoic acid isomers have been used with some success as chemotherapeutic agents, most recently with 13-cis retinoic acid showing impressive clinical efficacy in the paediatric malignancy neuroblastoma. The aim of this commentary is to review the evidence that 13-cis retinoic acid is a pro-drug, and consider the implications of retinoid metabolism and isomerisation for the further development of retinoic acid for cancer therapy. The low binding affinity of 13-cis retinoic acid for retinoic acid receptors, low activity in gene expression assays and the accumulation of the all-trans isomer in cells treated with 13-cis retinoic acid, coupled with the more-favourable pharmacokinetic profile of 13-cis retinoic acid compared to other isomers, suggest that intracellular isomerisation to all-trans retinoic acid is the key process underlying the biological activity of 13-cis retinoic acid. Intracellular metabolism of all-trans retinoic acid by a positive auto-regulatory loop may result in clinical resistance to retinoic acid. Agents that block or reduce the metabolism of all-trans retinoic acid are therefore attractive targets for drug development. Devising strategies to deliver 13-cis retinoic acid to tumour cells and facilitate the intracellular isomerisation of 13-cis retinoic acid, while limiting metabolism of all-trans retinoic acid, may have a major impact on the efficacy of 13-cis retinoic acid in paediatric oncology.
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NASA Technical Reports Server (NTRS)
Nonhebel, H. M.; Bandurski, R. S.
1984-01-01
Radiolabeled oxindole-3-acetic acid was metabolized by roots, shoots, and caryopses of dark grown Zea mays seedlings to 2,3-dihydro-7-hydroxy-2-oxo-1H indole-3-acetic acid-7'-O-beta-D-glycopyranoside with the simpler name of 7-hydroxyoxindole-3-acetic acid-glucoside. This compound was also formed from labeled indole-3-acetic acid supplied to intact seedlings and root segments. The glucoside of 7-hydroxyoxindole-3-acetic acid was also isolated as an endogenous compound in the caryopses and shoots of 4-day-old seedlings. It accumulates to a level of 4.8 nanomoles per plant in the kernel, more than 10 times the amount of oxindole-3-acetic acid. In the shoot it is present at levels comparable to that of oxindole-3-acetic acid and indole-3-acetic acid (62 picomoles per shoot). We conclude that 7-hydroxyoxindole-3-acetic acid-glucoside is a natural metabolite of indole-3-acetic acid in Z. mays seedlings. From the data presented in this paper and in previous work, we propose the following route as the principal catabolic pathway for indole-3-acetic acid in Zea seedlings: Indole-3-acetic acid --> Oxindole-3-acetic acid --> 7-Hydroxyoxindole-3-acetic acid --> 7-Hydroxyoxindole-3-acetic acid-glucoside.
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Yin, Yuli; Yan, Liang; Zhang, Zhaohui; Wang, Jing; Luo, Ningjing
2016-04-01
We describe novel cinnamic acid polydopamine-coated magnetic imprinted polymers for the simultaneous selective extraction of cinnamic acid, ferulic acid and caffeic acid from radix scrophulariae sample. The novel magnetic imprinted polymers were synthesized by surface imprinting polymerization using magnetic multi-walled carbon nanotubes as the support material, cinnamic acid as the template and dopamine as the functional monomer. The magnetic imprinted polymers were characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy and vibrating sample magnetometry. The results revealed that the magnetic imprinted polymers had outstanding magnetic properties, high adsorption capacity, selectivity and fast kinetic binding toward cinnamic acid, ferulic acid and caffeic acid. Coupled with high-performance liquid chromatography, the extraction conditions of the magnetic imprinted polymers as a magnetic solid-phase extraction sorbent were investigated in detail. The proposed imprinted magnetic solid phase extraction procedure has been used for the purification and enrichment of cinnamic acid, ferulic acid and caffeic acid successfully from radix scrophulariae extraction sample with recoveries of 92.4-115.0% for cinnamic acid, 89.4-103.0% for ferulic acid and 86.6-96.0% for caffeic acid. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Ren, Wan-Xia; Li, Pei-Jun; Zheng, Le; Fan, Shu-Xiu; Verhozina, V A
2009-02-15
A few researchers have reported on work concerning bioleaching of heavy-metal-contaminated soil using Acidithiobacillus ferrooxidans, since this acidophile is sensitive to dissolved low molecular weight (LMW) organic acids. Iron oxidation by A. ferrooxidans R2 as well as growth on ferrous iron was inhibited by a variety of dissolved LMW organic acids. Growth experiments with ferrous iron as an oxidant showed that the inhibition capability sequence was formic acid>acetic acid>propionic acid>oxalic acid>malic acid>citric acid. The concentrations that R2 might tolerate were formic acid 0.1mmolL(-1) (2mmolkg(-1)soil), acetic and propionic acids 0.4mmolL(-1) (8mmolkg(-1)soil), oxalic acid 2.0mmolL(-1) (40mmolkg(-1)soil), malic acid 20mmolL(-1) (400mmolkg(-1)soil), citric acid 40mmolL(-1) (800mmolkg(-1)soil), respectively. Although R2 was sensitive to organic acids, the concentrations of LMW organic acids in the contaminated soils were rather lower than the tolerable levels. Hence, it is feasible that R2 might be used for bioleaching of soils contaminated with metals or metals coupled with organic compounds because of the higher concentrations of LMW organic acids to which R2 is tolerant.
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Process for the preparation of lactic acid and glyceric acid
Jackson, James E [Haslett, MI; Miller, Dennis J [Okemos, MI; Marincean, Simona [Dewitt, MI
2008-12-02
Hexose and pentose monosaccharides are degraded to lactic acid and glyceric acid in an aqueous solution in the presence of an excess of a strongly anionic exchange resin, such as AMBERLITE IRN78 and AMBERLITE IRA400. The glyceric acid and lactic acid can be separated from the aqueous solution. Lactic acid and glyceric acid are staple articles of commerce.
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21 CFR 172.862 - Oleic acid derived from tall oil fatty acids.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Oleic acid derived from tall oil fatty acids. 172... FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.862 Oleic acid derived from tall oil fatty acids. The food additive oleic acid derived from tall oil fatty acids may be safely used in food and as...
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21 CFR 172.862 - Oleic acid derived from tall oil fatty acids.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Oleic acid derived from tall oil fatty acids. 172... FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.862 Oleic acid derived from tall oil fatty acids. The food additive oleic acid derived from tall oil fatty acids may be safely used in food and as...
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Installation Assessment of Frankford Arsenal.
1977-10-01
sulfate , sulfuric acid , ac ’solution 40 Hot water bath 41 Nickel plate Nickel sulfate and chloride sulfuric acid , acid ...solution 42 Chromium Copper plate Copper sulfate and sulfuric acid , acid solution 11-14 TABLE 11-2 (continued) Tank No. Plating Process Use Contents...46 Water rinse Water 47 Water rinse Water 48 Water rinse Water 49 Acid Chromic acid , acetic acid , nickel sulfate and sulfuric
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USDA-ARS?s Scientific Manuscript database
Walnuts contain polyunsaturated fatty acids (PUFAs), specifically the omega-6 fatty acid linoleic acid (LA) as well as the omega-3 fatty acid, alpha-linolenic acid (ALA), which can be metabolized to generate eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Previous research from our lab h...
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Batta, A K; Salen, G; Shefer, S
1985-01-01
We have examined the mechanism for the bacterial transformation of chenodeoxycholic acid and lithocholic acid into the corresponding 3 beta-hydroxy epimers with the use of 3 alpha- and 3 beta-tritiated bile acids. The 3-oxo bile acids were transformed into the 3 alpha- (85%) and 3 beta- (15%) hydroxy bile acids after 20-hr incubation with Clostridium perfringens. Approximately 75% radioactivity was recovered in the aqueous medium when [3 beta-3H]chenodeoxycholic acid or [3 beta-3H]lithocholic acid was incubated with the bacteria, and approximately 15% of radioactivity in the bile acid fraction was associated with the 3 alpha-position of the iso-bile acids. When [3 beta-3H]chenodeoxycholic acid was incubated with unlabeled 3-oxo-5 beta-cholanoic acid, tritiated litho- and iso-lithocholic acids were recovered. These results can be explained only when a 3-oxo intermediate is postulated, and the 3 beta-hydrogen in the bile acids is transferred by the bacterial coenzyme (NAD+ or NADP+) to the 3 alpha-position in the iso-bile acids during the reduction of the 3-oxo compounds.
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Rui, Liyun; Xie, Minhao; Hu, Bing; Zhou, Li; Saeeduddin, Muhammad; Zeng, Xiaoxiong
2017-08-15
Chlorogenic acid-chitosan conjugate was synthesized by introducing of chlorogenic acid onto chitosan with the aid of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and hydroxybenzotriazole. The data of UV-vis, FT-IR and NMR for chlorogenic acid-chitosan conjugates demonstrated the successful conjugation of chlorogenic acid with chitosan. Compared to chitosan, chlorogenic acid-chitosan conjugates exhibited increased solubility in distilled water, 1% acetic acid solution (v/v) or 50% ethanol solution (v/v) containing 0.5% acetic acid. Moreover, chlorogenic acid-chitosan conjugates showed dramatic enhancements in metal ion chelating activity, total antioxidant capacity, scavenging activities on 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) and superoxide radicals, inhibitory effects on lipid peroxidation and β-carotene-linoleic acid bleaching, and protective effect on H 2 O 2 -induced oxidative injury of PC12 cells. Particularly, chlorogenic acid-chitosan conjugate exhibited higher inhibitory effects on lipid peroxidation and β-carotene-linoleic acid bleaching than chlorogenic acid. The results suggested that chlorogenic acid-chitosan conjugates could serve as food supplements to enhance the function of foods in future. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Sequential injection redox or acid-base titration for determination of ascorbic acid or acetic acid.
Lenghor, Narong; Jakmunee, Jaroon; Vilen, Michael; Sara, Rolf; Christian, Gary D; Grudpan, Kate
2002-12-06
Two sequential injection titration systems with spectrophotometric detection have been developed. The first system for determination of ascorbic acid was based on redox reaction between ascorbic acid and permanganate in an acidic medium and lead to a decrease in color intensity of permanganate, monitored at 525 nm. A linear dependence of peak area obtained with ascorbic acid concentration up to 1200 mg l(-1) was achieved. The relative standard deviation for 11 replicate determinations of 400 mg l(-1) ascorbic acid was 2.9%. The second system, for acetic acid determination, was based on acid-base titration of acetic acid with sodium hydroxide using phenolphthalein as an indicator. The decrease in color intensity of the indicator was proportional to the acid content. A linear calibration graph in the range of 2-8% w v(-1) of acetic acid with a relative standard deviation of 4.8% (5.0% w v(-1) acetic acid, n=11) was obtained. Sample throughputs of 60 h(-1) were achieved for both systems. The systems were successfully applied for the assays of ascorbic acid in vitamin C tablets and acetic acid content in vinegars, respectively.
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Pyrite oxidation under simulated acid rain weathering conditions.
Zheng, Kai; Li, Heping; Wang, Luying; Wen, Xiaoying; Liu, Qingyou
2017-09-01
We investigated the electrochemical corrosion behavior of pyrite in simulated acid rain with different acidities and at different temperatures. The cyclic voltammetry, polarization curve, and electrochemical impedance spectroscopy results showed that pyrite has the same electrochemical interaction mechanism under different simulated acid rain conditions, regardless of acidity or environmental temperature. Either stronger acid rain acidity or higher environmental temperature can accelerate pyrite corrosion. Compared with acid rain having a pH of 5.6 at 25 °C, the prompt efficiency of pyrite weathering reached 104.29% as the acid rain pH decreased to 3.6, and it reached 125.31% as environmental temperature increased to 45 °C. Increasing acidity dramatically decreases the charge transfer resistance, and increasing temperature dramatically decreases the passivation film resistance, when other conditions are held constant. Acid rain always causes lower acidity mine drainage, and stronger acidity or high environmental temperatures cause serious acid drainage. The natural parameters of latitude, elevation, and season have considerable influence on pyrite weathering, because temperature is an important influencing factor. These experimental results are of direct significance for the assessment and management of sulfide mineral acid drainage in regions receiving acid rain.
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Niu, Huanqing; Chen, Yong; Xie, Jingjing; Chen, Xiaochun; Bai, Jianxin; Wu, Jinglan; Liu, Dong; Ying, Hanjie
2012-09-01
Simultaneous determination of organic acids using ion-exclusion liquid chromatography and ultraviolet detection is described. The chromatographic conditions are optimized when an Aminex HPX-87H column (300 × 7.8 mm) is employed, with a solution of 3 mmol/L sulfuric acid as eluent, a flow rate of 0.4 mL/min and a column temperature of 60°C. Eight organic acids (including orotic acid, α-ketoglutaric acid, citric acid, pyruvic acid, malic acid, succinic acid, lactic acid and acetic acid) and one nucleotide are successfully quantified. The calibration curves for these analytes are linear, with correlation coefficients exceeding 0.999. The average recovery of organic acids is in the range of 97.6% ∼ 103.1%, and the relative standard deviation is in the range of 0.037% ∼ 0.38%. The method is subsequently applied to obtain organic acid profiles of uridine 5'-monophosphate culture broth fermented from orotic acid by Saccharomyces cerevisiae. These data demonstrate the quantitative accuracy for nucleotide fermentation mixtures, and suggest that the method may also be applicable to other biological samples.
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The suppression of the N-nitrosating reaction by chlorogenic acid.
Kono, Y; Shibata, H; Kodama, Y; Sawa, Y
1995-01-01
N-Nitrosation of a model aromatic amine (2,3-diamino-naphthalene) by the N-nitrosating agent produced by nitrite in acidic solution was inhibited by a polyphenol, chlorogenic acid, which is an ester of caffeic acid quinic acid. Caffeic acid also inhibited the N-nitrosation, but quinic acid did not. 1,2-Benzenediols and 3,4-dihydroxybenzoic acid had inhibitory activities. Chlorogenic acid, caffeic acid, 1,2-benzenediols and 3,4-dihydroxybenzoic acid were able to scavenge the stable free radical, 1,1-diphenyl-2-picrylhydrazyl. Chlorogenic acid was found to be nitrated by acidic nitrite. The kinetic studies and the nitration observed only by bubbling of nitric oxide plus nitrogen dioxide gases indicated that the nitrating agent was nitrogen sesquioxide. The observations showed that the mechanism by which chlorogenic acid inhibited N-nitrosation of 2,3-diamino-naphthalene is due to its ability to scavenge the nitrosating agent, nitrogen sesquioxide. Chlorogenic acid may be effective not only in protecting against oxidative damage but also in inhibiting potentially mutagenic and carcinogenic reactions in vivo. PMID:8554543
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Gopal, Sanganamoni Chinna; Kaki, Shiva Shanker; Rao, Bhamidipati V S K; Poornachandra, Yedla; Kumar, Chityal Ganesh; Narayana Prasad, Rachapudi Badari
2014-01-01
Novel lipoamino acids were prepared with the coupling of sapienic acid [(Z)-6-hexadecenoic acid] with α - amino group of amino acids and the resulting N-sapienoyl amino acids were tested for their cytotoxicity activities against four cancer based cell lines. Initially, sapienic acid was synthesized by the Wittig coupling of triphenylphosphonium bromide salt of 6-bromohexanoic acid and decanal with a Z specific reagent. The prepared sapienic acid was subsequently converted to its acid chloride which was further coupled with amino acids by the Schotten-Baumann reaction to form N-sapienoyl amino acid conjugates. Structural characterization of the prepared N-sapienoyl amino acid derivatives was done by spectral data (IR, mass spectra and NMR). These lipoamino acid derivatives were screened for in vitro cytotoxicity evaluation. Cytotoxicity evaluation against four cancer cell lines showed that N-sapienoyl isoleucine was active against three cell lines whereas other derivatives either showed activity against only one or two cell lines with very moderate activity and two derivatives were observed to be inactive against the tested cell lines.
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Varughese, Sunil; Azim, Yasser; Desiraju, Gautam R
2010-09-01
A series of molecular complexes, both co-crystals and salts, of a triazole drug-alprazolam-with carboxylic acids, boric acid, boronic acids, and phenols have been analyzed with respect to heterosynthons present in the crystal structures. In all cases, the triazole ring behaves as an efficient hydrogen bond acceptor with the acidic coformers. The hydrogen bond patterns exhibited with aromatic carboxylic acids were found to depend on the nature and position of the substituents. Being a strong acid, 2,6-dihydroxybenzoic acid forms a salt with alprazolam. With aliphatic dicarboxylic acids alprazolam forms hydrates and the water molecules play a central role in synthon formation and crystal packing. The triazole ring makes two distinct heterosynthons in the molecular complex with boric acid. Boronic acids and phenols form consistent hydrogen bond patterns, and these are seemingly independent of the substitutional effects. Boronic acids form noncentrosymmetric cyclic synthons, while phenols form O--H...N hydrogen bonds with the triazole ring.
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Zazzi, Barbara C.; Crepeau, Kathryn L.; Fram, Miranda S.; Bergamaschi, Brian A.
2005-01-01
An analytical method for the determination of haloacetic acid formation potential of water samples has been developed by the U.S. Geological Survey California Water Science Center Sacramento Laboratory. The haloacetic acid formation potential is measured by dosing water samples with chlorine under specified conditions of pH, temperature, incubation time, darkness, and residual-free chlorine. The haloacetic acids formed are bromochloroacetic acid, bromodichloroacetic acid, dibromochloroacetic acid, dibromoacetic acid, dichloroacetic acid, monobromoacetic acid, monochloroacetic acid, tribromoacetic acid, and trichloroacetic acid. They are extracted, methylated, and then analyzed using a gas chromatograph equipped with an electron capture detector. Method validation experiments were performed to determine the method accuracy, precision, and detection limit for each of the compounds. Method detection limits for these nine haloacetic acids ranged from 0.11 to 0.45 microgram per liter. Quality-control practices include the use of blanks, quality-control samples, calibration verification standards, surrogate recovery, internal standard, matrix spikes, and duplicates.
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The effect of fish oil supplementation on brain DHA and EPA content and fatty acid profile in mice.
Valentini, Kelly J; Pickens, C Austin; Wiesinger, Jason A; Fenton, Jenifer I
2017-12-18
Supplementation with omega-3 (n-3) fatty acids may improve cognitive performance and protect against cognitive decline. However, changes in brain phospholipid fatty acid composition after supplementation with n-3 fatty acids are poorly described. The purpose of this study was to feed increasing n-3 fatty acids and characterise the changes in brain phospholipid fatty acid composition and correlate the changes with red blood cells (RBCs) and plasma in mice. Increasing dietary docosahexaenoic (DHA) and eicosapentaenoic acid (EPA) did not alter brain DHA. Brain EPA increased and total n-6 polyunsaturated fatty acids decreased across treatment groups, and correlated with fatty acid changes in the RBC (r > 0.7). Brain cis-monounsaturated fatty acids oleic and nervonic acid (p < .01) and saturated fatty acids arachidic, behenic, and lignoceric acid (p < .05) also increased. These brain fatty acid changes upon increasing n-3 intake should be further investigated to determine their effects on cognition and neurodegenerative disease.
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NASA Astrophysics Data System (ADS)
Mert, Ramazan; Bulut, Sait; Konuk, Muhsin
2015-01-01
In the present study, the effects of season on fatty acid composition, total lipids, and ω3/ω6 ratios of northern pike muscle lipids in Kizilirmak River (Kirikkale, Turkey) were investigated. A total of 35 different fatty acids were determined in gas chromatography. Among these, palmitic, oleic, and palmitoleic acids had the highest proportion. The main polyunsaturated fatty acids (PUFAs) were found to be docosahexaenoic acid, eicosapentaenoic acid, and arachidonic acid. There were more PUFAs than monounsaturated fatty acids (MUFA) in all seasons. Similarly, the percentages of ω3 fatty acids were higher than those of total ω6 fatty acids in the fatty acid composition. ω3/ω6 ratios were calculated as 1.53, 1.32, 1.97, and 1.71 in spring, summer, autumn and winter, respectively. Overall, we found that the fatty acid composition and ω3/ω6 fatty acid ratio in the muscle of northern pike were significantly influenced by season.
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Mechanism of Specific Inhibition of Phototropism by Phenylacetic Acid in Corn Seedling 1
Vierstra, Richard D.; Poff, Kenneth L.
1981-01-01
Using geotropism as a control for phototropism, compounds similar to phenylacetic acid that photoreact with flavins and/or have auxin-like activity were examined for their ability to specifically inhibit phototropism in corn seedlings using geotropism as a control. Results using indole-3-acetic acid, napthalene-1-acetic acid, naphthalene-2-acetic acid, phenylacetic acid, and β-phenylpyruvic acid suggest that such compounds will specifically inhibit phototropism primarily because of their photoreactivity with flavins and not their auxin activity. For example, strong auxins, indole-3-acetic acid and naphthalene-1-acetic acid, affected both tropic responses at all concentrations tested whereas weak auxins, phenylacetic acid and naphthalene-2-acetic acid, exhibited specific inhibition. In addition, the in vivo concentration of phenylacetic acid required to induce specificity was well below that required to stimulate coleoptile growth. Estimates of the percentage of photoreceptor pigment inactivated by phenylacetic acid (>10%) suggest that phenylacetic acid could be used to photoaffinity label the flavoprotein involved in corn seedling phototropism. PMID:16661774
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Amino acids in the Yamato carbonaceous chrondrite from Antarctica
NASA Technical Reports Server (NTRS)
Shimoyama, A.; Ponnamperuma, C.; Yanai, K.
1979-01-01
Evidence for the presence of amino acids of extraterrestrial origin in the Antarctic Yamato carbonaceous chrondrite is presented. Hydrolyzed and nonhydrolyzed water-extracted amino acid samples from exterior, middle and interior portions of the meteorite were analyzed by an amino acid analyzer and by gas chromatography of N-TFA-isopropyl amino acid derivatives. Nine protein and six nonprotein amino acids were detected in the meteorite at abundances between 34 and less than one nmole/g, with equal amounts in interior and exterior portions. Nearly equal abundances of the D and L enantiomers of alanine, aspartic acid and glutamic acid were found, indicating the abiotic, therefore extraterrestrial, origin of the amino acids. The Antarctic environment and the uniformity of protein amino acid abundances are discussed as evidence against the racemization of terrestrially acquired amino acids, and similarities between Yamato amino acid compositions and the amino acid compositions of the Murchison and Murray type II carbonaceous chrondrites are indicated.
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Hong, Ye-Ji; Ahn, Hyo-Ju; Shin, Jongdae; Lee, Joon H; Kim, Jin-Hoi; Park, Hwan-Woo; Lee, Sung Ki
2018-02-01
Dysregulated serum fatty acids are associated with a lipotoxic placental environment, which contributes to increased pregnancy complications via altered trophoblast invasion. However, the role of saturated and unsaturated fatty acids in trophoblastic autophagy has yet to be explored. Here, we demonstrated that prolonged exposure of saturated fatty acids interferes with the invasiveness of human extravillous trophoblasts. Saturated fatty acids (but not unsaturated fatty acids) inhibited the fusion of autophagosomes and lysosomes, resulting in the formation of intracellular protein aggregates. Furthermore, when the trophoblast cells were exposed to saturated fatty acids, unsaturated fatty acids counteracted the effects of saturated fatty acids by increasing degradation of autophagic vacuoles. Saturated fatty acids reduced the levels of the matrix metalloproteinases (MMP)-2 and MMP-9, while unsaturated fatty acids maintained their levels. In conclusion, saturated fatty acids induced decreased trophoblast invasion, of which autophagy dysfunction plays a major role. Copyright © 2017 Elsevier B.V. All rights reserved.
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Kato, Megumi; Yamazaki, Taichi; Kato, Hisashi; Yamanaka, Noriko; Takatsu, Akiko; Ihara, Toshihide
2017-01-01
To prepare metrologically traceable amino acid mixed standard solutions, it is necessary to determine the stability of each amino acid present in the mixed solutions. In the present study, we prepared amino acid mixed solutions using certified reference standards of 17 proteinogenic amino acids, and examined the stability of each of these amino acids in 0.1 N HCl. We found that the concentration of glutamic acid decreased significantly during storage. LC/MS analysis indicated that the instability of glutamic acid was due to the partial degradation of glutamic acid to pyroglutamic acid in 0.1 N HCl. Using accelerated degradation tests, we investigated several solvent compositions to improve the stability of glutamic acid in amino acid mixed solution, and determined that the change of the pH by diluting the mixed solution improved the stability of glutamic acid.
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Removal of acidic or basic α-amino acids in water by poorly water soluble scandium complexes.
Hayashi, Nobuyuki; Jin, Shigeki; Ujihara, Tomomi
2012-11-02
To recognize α-amino acids with highly polar side chains in water, poorly water soluble scandium complexes with both Lewis acidic and basic portions were synthesized as artificial receptors. A suspension of some of these receptor molecules in an α-amino acid solution could remove acidic and basic α-amino acids from the solution. The compound most efficient at preferentially removing basic α-amino acids (arginine, histidine, and lysine) was the receptor with 7,7'-[1,3-phenylenebis(carbonylimino)]bis(2-naphthalenesulfonate) as the ligand. The neutral α-amino acids were barely removed by these receptors. Removal experiments using a mixed amino acid solution generally gave results similar to those obtained using solutions containing a single amino acid. The results demonstrated that the scandium complex receptors were useful for binding acidic and basic α-amino acids.
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NASA Astrophysics Data System (ADS)
Zhang, Jing; Jin, Shouwen; Tao, Lin; Liu, Bin; Wang, Daqi
2014-08-01
Eight supramolecular complexes with 2-methylquinoline and acidic components as 4-aminobenzoic acid, 2-aminobenzoic acid, salicylic acid, 5-chlorosalicylic acid, 3,5-dinitrosalicylic acid, malic acid, sebacic acid, and 1,5-naphthalenedisulfonic acid were synthesized and characterized by X-ray crystallography, IR, mp, and elemental analysis. All of the complexes are organic salts except compound 2. All supramolecular architectures of 1-8 involve extensive classical hydrogen bonds as well as other noncovalent interactions. The results presented herein indicate that the strength and directionality of the classical hydrogen bonds (ionic or neutral) between acidic components and 2-methylquinoline are sufficient to bring about the formation of binary organic acid-base adducts. The role of weak and strong noncovalent interactions in the crystal packing is ascertained. These weak interactions combined, the complexes 1-8 displayed 2D-3D framework structure.
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The interaction of albumin and fatty-acid-binding protein with membranes: oleic acid dissociation.
Catalá, A
1984-10-01
Bovine serum albumin or fatty-acid-binding protein rapidly lose oleic acid when incubated in the presence of dimyristoyl lecithin liposomes. The phenomenon is dependent on vesicle concentration and no measurable quantities of protein are found associated with liposomes. Upon gel filtration on Sepharose CL-2B of incubated mixtures of microsomes containing [1-14C] oleic acid and albumin or fatty-acid-binding protein, association of fatty acid with the soluble proteins could be demonstrated. Both albumin and fatty-acid-binding protein stimulated the transfer of oleic acid from rat liver microsomes to egg lecithin liposomes. These results indicate that albumin is more effective in the binding of oleic acid than fatty-acid-binding protein, which allows a selective oleic acid dissociation during its interaction with membranes.
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Wang, Ling-Na; Wang, Wei; Hattori, Masao; Daneshtalab, Mohsen; Ma, Chao-Mei
2016-06-08
Chlorogenic acid is a well known natural product with important bioactivities. It contains an ester bond formed between the COOH of caffeic acid and the 3-OH of quinic acid. We synthesized a chlorogenic acid analogue, 3α-caffeoylquinic acid amide, using caffeic and quinic acids as starting materials. The caffeoylquinc acid amide was found to be much more stable than chlorogenic acid and showed anti-Hepatitis C virus (anti-HCV) activity with a potency similar to chlorogenic acid. The caffeoylquinc acid amide potently protected HepG2 cells against oxidative stress induced by tert-butyl hydroperoxide.
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21 CFR 178.3690 - Pentaerythritol adipate-stearate.
Code of Federal Regulations, 2011 CFR
2011-04-01
... adipic acid and stearic acid and its associated fatty acids (chiefly palmitic), with adipic acid comprising 14 percent and stearic acid and its associated acids (chiefly palmitic) comprising 71 percent of...: http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html. (2) Acid value...
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21 CFR 178.3690 - Pentaerythritol adipate-stearate.
Code of Federal Regulations, 2010 CFR
2010-04-01
... adipic acid and stearic acid and its associated fatty acids (chiefly palmitic), with adipic acid comprising 14 percent and stearic acid and its associated acids (chiefly palmitic) comprising 71 percent of...: http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html. (2) Acid value...
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Palombo, J D; DeMichele, S J; Boyce, P J; Lydon, E E; Liu, J W; Huang, Y S; Forse, R A; Mizgerd, J P; Bistrian, B R
1999-09-01
Because vasoactive eicosanoids derived from arachidonic acid present in immune cell phospholipids promote lung inflammation in critically ill patients, novel experimental diets containing eicosapentaenoic acid from fish oil and gamma-linolenic acid from borage oil have been designed to limit arachidonic acid metabolism. However, excess dietary eicosapentaenoic acid impairs superoxide formation and bacterial killing by immune cells. The present study determined whether short-term enteral feeding with diets enriched with either eicosapentaenoic acid alone or in combination with gamma-linolenic acid would modulate alveolar macrophage eicosanoid synthesis without compromising bactericidal function. Prospective, randomized, controlled, blinded study. University medical center. Adult male Sprague-Dawley rats. Rats underwent surgical placement of a gastroduodenal feeding catheter and were randomly assigned to receive one of three high-fat (55.2% of total calories), low-carbohydrate diets containing isocaloric amounts of lipids for 4 days. The control diet was enriched with linoleic acid, whereas the two test diets were low in linoleic acid and enriched with either 5 mole % eicosapentaenoic acid alone or in combination with 5 mole % gamma-linolenic acid. Alveolar macrophages were then procured to assess phospholipid fatty acid composition, eicosanoid synthesis after stimulation with endotoxin, superoxide formation and phagocytosis by flow cytometry, and killing of Staphylococcus aureus Alveolar macrophage levels of arachidonic acid were significantly (p < .01) lower and levels of eicosapentaenoic and dihomo-gamma-linolenic acids were higher after feeding the eicosapentaenoic and gamma-linolenic acid diet vs. the linoleic acid diet. Ratios of thromboxane B2,/B3, leukotriene B4/B5, and prostaglandin E2/E1 were reduced in the macrophages from rats given either the eicosapentaenoic acid or eicosapentaenoic acid with gamma-linolenic acid diet compared with ratios from rats given the linoleic acid diet. Macrophages from rats given the eicosapentaenoic with gamma-linolenic acid diet released 35% or 24% more prostaglandin E1 than macrophages from rats given either the linoleic acid or the eicosapentaenoic acid diet, respectively. Macrophage superoxide generation, phagocytosis of opsonized zymosan, and killing of S. aureus were similar irrespective of dietary treatment. Short-term enteral feeding with an eicosapentaenoic acid-enriched or eicosapentaenoic with gamma-linolenic acid-enriched diet rapidly modulated the fatty acid composition of alveolar macrophage phospholipids, promoted a shift toward formation of less inflammatory eicosanoids by stimulated macrophages, but did not impair alveolar macrophage bactericidal function relative to responses observed after feeding a linoleic acid diet.
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Hossain, Md Sharoare; Afrose, Sadia; Sawada, Tomio; Hamano, Koh-Ichi; Tsujii, Hirotada
2010-03-01
For understanding the roles of fatty acids on the induction of acrosome reaction which occurs under association of cholesterol efflux and PKA or PKC pathways in boar spermatozoa, metabolic fate of alone and combined radiolabeled 14 C-oleic acid and 3 H-linoleic acid incorporated in the sperm was compared, and behavior of cholesterol and effects of PKA and PKC inhibitors upon fatty acid-induced acrosome reaction were examined. Semen was collected from a Duroc boar, and the metabolic activities of fatty acids in the spermatozoa were measured using radioactive compounds and thin layer chromatography. Cholesterol efflux was measured with a cholesterol determination assay kit. Participation of fatty acids on the AR through PKA and PKC pathways was evaluated using a specific inhibitor of these enzymes. Incorporation rate of 14 C-oleic acid into the sperm lipids was significantly higher than that of 3 H-linoleic acid ( P < 0.05). The oxidation of 14 C-oleic acid was higher in combined radiolabeling rather than in one. The highest amounts of 3 H-linoleic acid and 14 C-oleic acid were recovered mainly in the triglycerides and phospholipids fraction, and 14 C-oleic acid distribution was higher than the 3 H-linoleic acid in both labeled ( P < 0.05) sperm lipids. In the 3 H-linoleic and 14 C-oleic acid combined radiolabeling, the incorporation rate of the radioactive fatty acids in all the lipid fractions increased 15 times more than the alone radiolabeling. Boar sperm utilize oleic acid to generate energy for hyperactivation ( P < 0.05). Supplementation of arachidonic acid significantly increased ( P < 0.05) cholesterol efflux in sperm. When spermatozoa were incubated with PKA or PKC inhibitors, there was a significant reduction of arachidonic acid-induced acrosome reaction (AR) ( P < 0.05), and inhibition by PKA inhibitor is stronger than that by PKC inhibitor. Incorporation of unsaturated fatty acids, especially oleic acid, into triglycerides and phospholipids provides prerequisite energy for AR. Cholesterol efflux by arachidonic acid triggers AR. Arachidonic acid activated PKA and PKC pathway participate in induction of the AR.
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Contribution of acidic components to the total acid number (TAN) of bio-oil
Park, Lydia K-E.; Liu, Jiaojun; Yiacoumi, Sotira; ...
2017-03-28
Bio-oil or pyrolysis oil — a product of thermochemical decomposition of biomass under oxygen-limited conditions — holds great potential to be a substitute for nonrenewable fossil fuels. But, its high acidity, which is primarily due to the degradation of hemicelluloses, limits its applications. For the evaluation of bio-oil production and treatment, it is essential to accurately measure the acidity of bio-oil. The total acid number (TAN), which is defined as the amount of potassium hydroxide needed to titrate one gram of a sample and has been established as an ASTM method to measure the acidity of petroleum products, has beenmore » employed to investigate the acidity of bio-oil. The TAN values of different concentrations of bio-oil components such as standard solutions of acetic acid, propionic acid, vanillic acid, hydroxybenzoic acid, syringic acid, hydroxymethylfurfural, and phenol were analyzed according to the ASTM D664 standard method. Our method showed the same linear relationship between the TAN values and the molar concentrations of acetic, propionic, and hydroxybenzoic acids. A different linear relationship was found for vanillic acid, due to the presence of multiple functional groups that can contribute to the TAN value. Furthermore, the influence of the titration solvent on the TAN values has been determined by comparing the TAN values and titration curves obtained from the standard method with results from the TAN analysis in aqueous environment and with equilibrium modeling results. Aqueous bio-oil samples with a known amount of acetic acid added were also analyzed. The additional acetic acid in bio-oil samples caused a proportional increase in the TAN values. These results of this research indicate that the TAN value of a sample with acids acting as monoprotic acids in the titration solvent can be converted to the molar concentration of total acids. For a sample containing acids that act as diprotic and polyprotic acids, however, its TAN value cannot be simply converted to the molar concentration of total acids because these acids have a stronger contribution to the TAN values than the contribution of monoprotic acids.« less
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Contribution of acidic components to the total acid number (TAN) of bio-oil
DOE Office of Scientific and Technical Information (OSTI.GOV)
Park, Lydia K-E.; Liu, Jiaojun; Yiacoumi, Sotira
Bio-oil or pyrolysis oil — a product of thermochemical decomposition of biomass under oxygen-limited conditions — holds great potential to be a substitute for nonrenewable fossil fuels. But, its high acidity, which is primarily due to the degradation of hemicelluloses, limits its applications. For the evaluation of bio-oil production and treatment, it is essential to accurately measure the acidity of bio-oil. The total acid number (TAN), which is defined as the amount of potassium hydroxide needed to titrate one gram of a sample and has been established as an ASTM method to measure the acidity of petroleum products, has beenmore » employed to investigate the acidity of bio-oil. The TAN values of different concentrations of bio-oil components such as standard solutions of acetic acid, propionic acid, vanillic acid, hydroxybenzoic acid, syringic acid, hydroxymethylfurfural, and phenol were analyzed according to the ASTM D664 standard method. Our method showed the same linear relationship between the TAN values and the molar concentrations of acetic, propionic, and hydroxybenzoic acids. A different linear relationship was found for vanillic acid, due to the presence of multiple functional groups that can contribute to the TAN value. Furthermore, the influence of the titration solvent on the TAN values has been determined by comparing the TAN values and titration curves obtained from the standard method with results from the TAN analysis in aqueous environment and with equilibrium modeling results. Aqueous bio-oil samples with a known amount of acetic acid added were also analyzed. The additional acetic acid in bio-oil samples caused a proportional increase in the TAN values. These results of this research indicate that the TAN value of a sample with acids acting as monoprotic acids in the titration solvent can be converted to the molar concentration of total acids. For a sample containing acids that act as diprotic and polyprotic acids, however, its TAN value cannot be simply converted to the molar concentration of total acids because these acids have a stronger contribution to the TAN values than the contribution of monoprotic acids.« less
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Zhou, Jing; Ma, Hong-yue; Fan, Xin-sheng; Xiao, Wei; Wang, Tuan-jie
2012-10-01
To investigate the mechanism of binding of human serum albumin (HSA) with potential sensitinogen, including chlorogenic acid and two isochlorogenic acids (3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid). By using the docking algorithm of computer-aided molecular design and the Molegro Virtual Docker, the crystal structures of HSA with warfarin and diazepam (Protein Data Bank ID: 2BXD and 2BXF) were selected as molecular docking receptors of HSA sites I and II. According to docking scores, key residues and H-bond, the molecular docking mode was selected and confirmed. The molecular docking of chlorogenic acid and two isochlorogenic acids on sites I and II was compared based on the above design. The results from molecular docking indicated that chlorogenic acid, 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid could bind to HSA site I by high affinity scores of -112.3, -155.3 and -153.1, respectively. They could bind to site II on HSA by high affinity scores of -101.7, -138.5 and -133.4, respectively. In site I, two isochlorogenic acids interacted with the key apolar side-chains of Leu238 and Ala291 by higher affinity scores than chlorogenic acid. Furthermore, the H-bonds of isochlorogenic acids with polar residues inside the pocket and at the entrance of the pocket were different from chlorogenic acid. Moreover, the second coffee acyl of isochlorogenic acid occupied the right-hand apolar compartment in the pocket of HSA site I. In site I, the second coffee acyl of isochlorogenic acid formed the H-bonds with polar side-chains, which contributed isochlorogenic acid to binding with site II of HSA. The isochlorogenic acids with two coffee acyls have higher binding abilities with HSA than chlorogenic acid with one coffee acyl, suggesting that isochlorogenic acids binding with HSA may be sensitinogen.
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Cao, Xiaochuang; Ma, Qingxu; Zhong, Chu; Yang, Xin; Zhu, Lianfeng; Zhang, Junhua; Jin, Qianyu; Wu, Lianghuan
2016-01-01
Amino acids are important sources of soil organic nitrogen (N), which is essential for plant nutrition, but detailed information about which amino acids predominant and whether amino acid composition varies with elevation is lacking. In this study, we hypothesized that the concentrations of amino acids in soil would increase and their composition would vary along the elevational gradient of Taibai Mountain, as plant-derived organic matter accumulated and N mineralization and microbial immobilization of amino acids slowed with reduced soil temperature. Results showed that the concentrations of soil extractable total N, extractable organic N and amino acids significantly increased with elevation due to the accumulation of soil organic matter and the greater N content. Soil extractable organic N concentration was significantly greater than that of the extractable inorganic N (NO3--N + NH4+-N). On average, soil adsorbed amino acid concentration was approximately 5-fold greater than that of the free amino acids, which indicates that adsorbed amino acids extracted with the strong salt solution likely represent a potential source for the replenishment of free amino acids. We found no appreciable evidence to suggest that amino acids with simple molecular structure were dominant at low elevations, whereas amino acids with high molecular weight and complex aromatic structure dominated the high elevations. Across the elevational gradient, the amino acid pool was dominated by alanine, aspartic acid, glycine, glutamic acid, histidine, serine and threonine. These seven amino acids accounted for approximately 68.9% of the total hydrolyzable amino acid pool. The proportions of isoleucine, tyrosine and methionine varied with elevation, while soil major amino acid composition (including alanine, arginine, aspartic acid, glycine, histidine, leucine, phenylalanine, serine, threonine and valine) did not vary appreciably with elevation (p>0.10). The compositional similarity of many amino acids across the elevational gradient suggests that soil amino acids likely originate from a common source or through similar biochemical processes.
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Yang, Xin; Zhu, Lianfeng; Zhang, Junhua; Jin, Qianyu; Wu, Lianghuan
2016-01-01
Amino acids are important sources of soil organic nitrogen (N), which is essential for plant nutrition, but detailed information about which amino acids predominant and whether amino acid composition varies with elevation is lacking. In this study, we hypothesized that the concentrations of amino acids in soil would increase and their composition would vary along the elevational gradient of Taibai Mountain, as plant-derived organic matter accumulated and N mineralization and microbial immobilization of amino acids slowed with reduced soil temperature. Results showed that the concentrations of soil extractable total N, extractable organic N and amino acids significantly increased with elevation due to the accumulation of soil organic matter and the greater N content. Soil extractable organic N concentration was significantly greater than that of the extractable inorganic N (NO3−-N + NH4+-N). On average, soil adsorbed amino acid concentration was approximately 5-fold greater than that of the free amino acids, which indicates that adsorbed amino acids extracted with the strong salt solution likely represent a potential source for the replenishment of free amino acids. We found no appreciable evidence to suggest that amino acids with simple molecular structure were dominant at low elevations, whereas amino acids with high molecular weight and complex aromatic structure dominated the high elevations. Across the elevational gradient, the amino acid pool was dominated by alanine, aspartic acid, glycine, glutamic acid, histidine, serine and threonine. These seven amino acids accounted for approximately 68.9% of the total hydrolyzable amino acid pool. The proportions of isoleucine, tyrosine and methionine varied with elevation, while soil major amino acid composition (including alanine, arginine, aspartic acid, glycine, histidine, leucine, phenylalanine, serine, threonine and valine) did not vary appreciably with elevation (p>0.10). The compositional similarity of many amino acids across the elevational gradient suggests that soil amino acids likely originate from a common source or through similar biochemical processes. PMID:27337100
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40 CFR 721.3620 - Fatty acid amine condensate, polycarboxylic acid salts.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Fatty acid amine condensate... Specific Chemical Substances § 721.3620 Fatty acid amine condensate, polycarboxylic acid salts. (a... a fatty acid amine condensate, polycarboxylic acid salts. (PMN P-92-445) is subject to reporting...
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Improved zeolite regeneration processes for preparing saturated branched-chain fatty acids
USDA-ARS?s Scientific Manuscript database
Ferrierite zeolite solid is an excellent catalyst for the skeletal isomerization of unsaturated linear-chain fatty acids (i.e., oleic acid) to unsaturated branched-chain fatty acids (i.e., iso-oleic acid) follow by hydrogenation to give saturated branched-chain fatty acids (i.e., isostearic acid). ...
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40 CFR 721.3620 - Fatty acid amine condensate, polycarboxylic acid salts.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Fatty acid amine condensate... Specific Chemical Substances § 721.3620 Fatty acid amine condensate, polycarboxylic acid salts. (a... a fatty acid amine condensate, polycarboxylic acid salts. (PMN P-92-445) is subject to reporting...
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Ramirez-Hernandez, Alejandra; Brashears, Mindy M; Sanchez-Plata, Marcos X
2018-01-01
The poultry processing industry has been undergoing a series of changes as it modifies processing practices to comply with new performance standards for chicken parts and comminuted poultry products. The regulatory approach encourages the use of intervention strategies to prevent and control foodborne pathogens in poultry products and thus improve food safety and protect human health. The present studies were conducted to evaluate the efficacy of antimicrobial interventions for reducing Salmonella on inoculated chicken parts under simulated commercial processing conditions. Chicken pieces were inoculated by immersion in a five-strain Salmonella cocktail at 6 log CFU/mL and then treated with organic acids and oxidizing agents on a commercial rinsing conveyor belt. The efficacy of spraying with six different treatments (sterile water, lactic acid, acetic acid, buffered lactic acid, acetic acid in combination with lactic acid, and peracetic acid) at two concentrations was evaluated on skin-on and skin-off chicken thighs at three application temperatures. Skinless chicken breasts were used to evaluate the antimicrobial efficacy of lactic acid and peracetic acid. The color stability of treated and untreated chicken parts was assessed after the acid interventions. The lactic acid and buffered lactic acid treatments produced the greatest reductions in Salmonella counts. Significant differences between the control and water treatments were identified for 5.11% lactic acid and 5.85% buffered lactic acid in both skin-on and skin-off chicken thighs. No significant effect of treatment temperature for skin-on chicken thighs was found. Lactic acid and peracetic acid were effective agents for eluting Salmonella cells attached to chicken breasts.
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Wesson, Donald E; Pruszynski, Jessica; Cai, Wendy; Simoni, Jan
2017-04-01
Diets high in acid of developed societies that do not cause metabolic acidosis in patients with chronic kidney disease nevertheless appear to cause acid retention with associated morbidity, particularly in those with reduced glomerular filtration rate. Here we used a rat 2/3 nephrectomy model of chronic kidney disease to study induction and maintenance of acid retention and its consequences on indicators of kidney and bone injury. Dietary acid was increased in animals eating base-producing soy protein with acid-producing casein and in casein-eating animals with added ammonium chloride. Using microdialysis to measure the kidney cortical acid content, we found that nephrectomized animals had greater acid retention than sham-operated animals when both ate the soy diet. Each increment in dietary acid further increased acid retention more in nephrectomized than in sham rats. Nephrectomized and sham animals achieved similar steady-state daily urine net acid excretion in response to increments in dietary acid but nephrectomized animals took longer to do so, contributing to greater acid retention that was maintained until the increased dietary acid was stopped. Acid retention was associated with increased urine excretion of both N-acetyl-β-D-glucosaminidase and deoxypyridinoline, greater in nephrectomized than control rats, consistent with kidney tubulointerstitial and bone matrix injury, respectively. Greater acid retention in nephrectomized than control animals was induced by a slower increase in urinary net acid excretion rate in response to the increment in dietary acid and also maintained until the dietary acid increment was stopped. Thus, acid retention increased biomarkers of kidney and bone injury in the urine, supporting untoward consequences to these two tissues. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Zhong; Matus, Myrna H; Velazquez, Hector A
Gas-phase acidities (GA or ΔG acid) for the two most acidic common amino acids, aspartic acid and glutamic acid, have been determined for the first time. Because of the amide linkage’s importance in peptides and as an aid in studying side chain versus main chain deprotonation, aspartic acid amide and glutamic acid amide were also studied. Experimental GA values were measured by proton transfer reactions in an electrospray ionization/Fourier transform ion cyclotron resonance mass spectrometer. Calculated GAs were obtained by density functional and molecular orbital theory approaches. The best agreement with experiment was found at the G3MP2 level; the MP2/CBSmore » and B3LYP/aug-cc-pVDZ results are 3–4 kcal/mol more acidic than the G3MP2 results. Experiment shows that aspartic acid is more acidic than glutamic acid by ca. 3 kcal/mol whereas the G3MP2 results show a smaller acidity difference of 0.2 kcal/mol. Similarly, aspartic acid amide is experimentally observed to be ca. 2 kcal/mol more acidic than glutamic acid amide whereas the G3MP2 results show a correspondingly smaller energy difference of 0.7 kcal/mol. The computational results clearly show that the anions are all ring-like structures with strong hydrogen bonds between the OH or NH 2 groups and the CO 2 - group from which the proton is removed. The two amino acids are main-chain deprotonated. In addition, use of the COSMO model for the prediction of the free energy differences in aqueous solution gave values in excellent agreement with the most recent experimental values for pK a. Glutamic acid is predicted to be more acidic than aspartic acid in aqueous solution due to differential solvation effects.« less
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Differential regulation of placental amino acid transport by saturated and unsaturated fatty acids.
Lager, Susanne; Jansson, Thomas; Powell, Theresa L
2014-10-15
Fatty acids are critical for normal fetal development but may also influence placental function. We have previously reported that oleic acid (OA) stimulates amino acid transport in primary human trophoblasts (PHTs). In other tissues, saturated and unsaturated fatty acids have distinct effects on cellular signaling, for instance, palmitic acid (PA) but not OA reduces IκBα expression. We hypothesized that saturated and unsaturated fatty acids differentially affect trophoblast amino acid transport and cellular signaling. To test this hypothesis, PHTs were cultured in docosahexaenoic acid (DHA; 50 μM), OA (100 μM), or PA (100 μM). DHA and OA were also combined to test whether DHA could counteract the OA stimulatory effect on amino acid transport. The effects of fatty acids were compared against a vehicle control. Amino acid transport was measured by isotope-labeled tracers. Activation of inflammatory-related signaling pathways and the mechanistic target of rapamycin (mTOR) pathway were determined by Western blot analysis. Exposure of PHTs to DHA for 24 h reduced amino acid transport and phosphorylation of p38 MAPK, STAT3, mTOR, eukaryotic initiation factor 4E-binding protein 1, and ribosomal protein (rp)S6. In contrast, OA increased amino acid transport and phosphorylation of ERK, mTOR, S6 kinase 1, and rpS6. The combination of DHA with OA increased amino acid transport and rpS6 phosphorylation. PA did not affect amino acid transport but reduced IκBα expression. In conclusion, these fatty acids differentially regulated placental amino acid transport and cellular signaling. Taken together, these findings suggest that dietary fatty acids could alter the intrauterine environment by modifying placental function, thereby having long-lasting effects on the developing fetus. Copyright © 2014 the American Physiological Society.
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Li, Zheng-Quan; Ma, Hao; Mao, Yu-Ding; Feng, Tao
2014-02-01
Using long-term observation data of acid rain at Lin'an Regional Background Station (Lin'an RBS), this paper studied the interannual and monthly variations of acid rain, the reasons for the variations, and the relationships between acid rain and meteorological factors. The results showed that interannual variation of acid rain at Lin'an RBS had a general increasing trend in which there were two obvious intensifying processes and two distinct weakening processes, during the period ranging from 1985 to 2012. In last two decades, the monthly variation of acid rain at Lin'an RBS indicated that rain acidity and frequency of severe acid rain were increasing but the frequency of weak acid rain was decreasing when moving towards bilateral side months of July. Acid rain occurrence was affected by rainfall intensity, wind speed and wind direction. High frequency of severe acid rain and low frequency of weak acid rain were on days with drizzle, but high frequency of weak acid rain and low frequency of severe acid rain occurred on rainstorm days. With wind speed upgrading, the frequency of acid rain and the proportion of severe acid rain were declining, the pH value of precipitation was reducing too. Another character is that daily dominant wind direction of weak acid rain majorly converged in S-W section ,however that of severe acid rain was more likely distributed in N-E section. The monthly variation of acid rain at Lin'an RBS was mainly attributed to precipitation variation, the increasing and decreasing of monthly incoming wind from SSE-WSW and NWN-ENE sections of wind direction. The interannual variation of acid rain could be due to the effects of energy consumption raising and significant green policies conducted in Zhejiang, Jiangsu and Shanghai.
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Kocatepe, Demet; Turan, Hülya
2012-06-01
The proximate and fatty acid compositions of the commercially important fish species (Engraulis encrasicolus, Alosa alosa, Belone belone, Scorpaena porcus, Pomatomus saltatrix, Mullus barbatus) from the Sinop region of the Black Sea were examined. The fat contents ranged from 1.26% (for scorpion fish) to 18.12% (for shad). The protein contents were min 14.54% (for red mullet) and maximum 20.26% (for belone). The fatty acid compositions of the fish ranged from 27.83 to 35.91% for saturated fatty acids, 19.50-33.80% for monounsaturated fatty acids and 15.25-40.02% for polyunsaturated fatty acids. Among the saturated fatty acids, palmitic acid (16:0) (17.75-22.20%) was the dominant fatty acid for all the fish species. As a second saturated fatty acid, myristic acid (14:0) was observed in four of the fish species and its content ranged from 4.72 to 7.31%. Whereas, for the other two fish species, the second saturated fatty acid was stearic acid (18:0) ranging between 4.54 and 10.64%. Among the monounsaturated fatty acids, those occurring in the highest proportions were oleic acid (18:1n-9c) (11.67-22.45%) and palmitoleic acid (16:1) (4.50-9.40%). Docosahexaenoic acid (22:6n-3) (5.41-28.52%), eicosapentaenoic acid (20:5n-3) (4.68-11.06) and linoleic acid (18:2n-6) (1.38-3.49%) were dominant polyunsaturated fatty acids, respectively. All the species, in particular the belone, the anchovy and the shad had high levels of the n-3 series.
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Alleviation of ascorbic acid-induced gastric high acidity by calcium ascorbate in vitro and in vivo.
Lee, Joon-Kyung; Jung, Sang-Hyuk; Lee, Sang-Eun; Han, Joo-Hui; Jo, Eunji; Park, Hyun-Soo; Heo, Kyung-Sun; Kim, Deasun; Park, Jeong-Sook; Myung, Chang-Seon
2018-01-01
Ascorbic acid is one of the most well-known nutritional supplement and antioxidant found in fruits and vegetables. Calcium ascorbate has been developed to mitigate the gastric irritation caused by the acidity of ascorbic acid. The aim of this study was to compare calcium ascorbate and ascorbic acid, focusing on their antioxidant activity and effects on gastric juice pH, total acid output, and pepsin secretion in an in vivo rat model, as well as pharmacokinetic parameters. Calcium ascorbate and ascorbic acid had similar antioxidant activity. However, the gastric fluid pH was increased by calcium ascorbate, whereas total acid output was increased by ascorbic acid. In the rat pylorus ligation-induced ulcer model, calcium ascorbate increased the gastric fluid pH without changing the total acid output. Administration of calcium ascorbate to rats given a single oral dose of 100 mg/kg as ascorbic acid resulted in higher plasma concentrations than that from ascorbic acid alone. The area under the curve (AUC) values of calcium ascorbate were 1.5-fold higher than those of ascorbic acid, and the C max value of calcium ascorbate (91.0 ng/ml) was higher than that of ascorbic acid (74.8 ng/ml). However, their T max values were similar. Thus, although calcium ascorbate showed equivalent antioxidant activity to ascorbic acid, it could attenuate the gastric high acidity caused by ascorbic acid, making it suitable for consideration of use to improve the side effects of ascorbic acid. Furthermore, calcium ascorbate could be an appropriate antioxidant substrate, with increased oral bioavailability, for patients with gastrointestinal disorders.
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Effect of 2 ppm ozone exposure on rat lung lipid fatty acids
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rabinowitz, J.L.; Bassett, D.J.
Based on in vitro studies, the initial damage to lung cells by ozone exposure is believed to result in part from the breakdown of lipid polyunsaturated fatty acids to aldehydes, ozonides, and peroxides. The present study measured lipid breakdown products in lungs isolated from rats pretreated with (1-/sup 14/C)acetate 12 h before exposure for 4 h to either air or 2 ppm ozone. Lipid fatty acid breakdown was indicated by a 112% increase in thiobarbituric acid-reactive substances on ozone exposure and by changes in chemical and radioactive measurements of mono- and dicarboxylic acids formed by treatment of lipid fractions withmore » hydrogen peroxide. Ozone exposure resulted in a 63% increase in recovery of short-chain fatty acids accounted for by increased recoveries of malonic acid by 37%, hexanoic acid by 47%, nonanoic acid by 118%, and azelaic acid by 107%. Recovery of glutaric acid was enhanced 15-fold by ozone exposure. Although decreases in tissue arachidonic acid could not be detected, oleic acid was significantly decreased by 36%. Recovery of radiolabel as short-chain fatty acids was increased by 65% on ozone exposure and was mainly accounted for by enhanced labeling of nonanoic and glutaric acid fractions. The failure to observe significant increases in /sup 14/C recovery in the other fractions suggested ozone-induced breakdown of unlabeled fatty acids. These results demonstrate the cleavage of unsaturated fatty acid double bonds following in vivo exposure of lungs to ozone. Breakdown of arachidonic and oleic acids was specifically identified by increased recoveries of glutaric and nonanoic acids, respectively.« less
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Alleviation of ascorbic acid-induced gastric high acidity by calcium ascorbate in vitro and in vivo
Lee, Joon-Kyung; Jung, Sang-Hyuk; Lee, Sang-Eun; Han, Joo-Hui; Jo, Eunji; Park, Hyun-Soo; Heo, Kyung-Sun; Kim, Deasun
2018-01-01
Ascorbic acid is one of the most well-known nutritional supplement and antioxidant found in fruits and vegetables. Calcium ascorbate has been developed to mitigate the gastric irritation caused by the acidity of ascorbic acid. The aim of this study was to compare calcium ascorbate and ascorbic acid, focusing on their antioxidant activity and effects on gastric juice pH, total acid output, and pepsin secretion in an in vivo rat model, as well as pharmacokinetic parameters. Calcium ascorbate and ascorbic acid had similar antioxidant activity. However, the gastric fluid pH was increased by calcium ascorbate, whereas total acid output was increased by ascorbic acid. In the rat pylorus ligation-induced ulcer model, calcium ascorbate increased the gastric fluid pH without changing the total acid output. Administration of calcium ascorbate to rats given a single oral dose of 100 mg/kg as ascorbic acid resulted in higher plasma concentrations than that from ascorbic acid alone. The area under the curve (AUC) values of calcium ascorbate were 1.5-fold higher than those of ascorbic acid, and the Cmax value of calcium ascorbate (91.0 ng/ml) was higher than that of ascorbic acid (74.8 ng/ml). However, their Tmax values were similar. Thus, although calcium ascorbate showed equivalent antioxidant activity to ascorbic acid, it could attenuate the gastric high acidity caused by ascorbic acid, making it suitable for consideration of use to improve the side effects of ascorbic acid. Furthermore, calcium ascorbate could be an appropriate antioxidant substrate, with increased oral bioavailability, for patients with gastrointestinal disorders. PMID:29302210
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Davidson, Michael H
2013-12-01
Fish oil contains a complex mixture of omega-3 fatty acids, which are predominantly eicosapentaenoic acid (EPA), docosapentaenoic acid, and docosahexaenoic acid (DHA). Each of these omega-3 fatty acids has distinct biological effects that may have variable clinical effects. In addition, plasma levels of omega-3 fatty acids are affected not only by dietary intake, but also by the polymorphisms of coding genes fatty acid desaturase 1-3 for the desaturase enzymes that convert short-chain polyunsaturated fatty acids to long-chain polyunsaturated fatty acids. The clinical significance of this new understanding regarding the complexity of omega-3 fatty acid biology is the purpose of this review. FADS polymorphisms that result in either lower levels of long-chain omega-3 fatty acids or higher levels of long-chain omega-6 polyunsaturated fatty acids, such as arachidonic acid, are associated with dyslipidemia and other cardiovascular risk factors. EPA and DHA have differences in their effects on lipoprotein metabolism, in which EPA, with a more potent peroxisome proliferator-activated receptor-alpha effect, decreases hepatic lipogenesis, whereas DHA not only enhances VLDL lipolysis, resulting in greater conversion to LDL, but also increases HDL cholesterol and larger, more buoyant LDL particles. Overall, these results emphasize that blood concentrations of individual long-chain polyunsaturated fatty acids, which reflect both dietary intake and metabolic influences, may have independent, but also complementary- biological effects and reinforce the need to potentially provide a complex mixture of omega-3 fatty acids to maximize cardiovascular risk reduction.
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Topical Acne Treatments and Pregnancy
... are benzoyl peroxide, azelaic acid, glycolic acid, and salicylic acid. Prescription acne medications include tretinoin, adapalene, dapsone, and ... ACOG) recommends topical benzoyl peroxide, azelaic acid, topical salicylic acid and glycolic acid for treatment of acne in ...
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Meyer, S. L. F.; Huettel, R. N.
1996-01-01
A mutant strain of the fungus Verticillium lecanii and selected bioregulators of Heterodera glycines were evaluated for their potential to reduce population densities of the nematode on soybean under greenhouse conditions. The bioregulators tested were the H. glycines sex pheromone vanillic acid and the pheromone analogs syringic acid, isovanillic acid, ferulic acid, 4-hydroxy-3-methoxybenzonitrile, and methyl vanillate. A V. lecanii-vanillic acid combination and a V. lecanii-syringic acid combination were also applied as treatments. Syringic acid, 4-hydroxy-3-methoxybenzonitrile, V. lecanii, V. lecanii-vanillic acid, and V. lecanii-syringic acid significantly reduced nematode population densities in the greenhouse tests. Results with vanillic acid, isovanillic acid, and ferulic acid treatments were variable. Methyl vanillate did not significantly reduce cyst nematode population densities in the greenhouse tests. PMID:19277343
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Removal of lead by apatite and its stability in the presence of organic acids.
Katoh, Masahiko; Makimura, Akihiko; Sato, Takeshi
2016-12-01
In this study, lead sorption and desorption tests were conducted with apatite and organic acids (i.e. citric, malic, and formic acids) to understand lead removal by apatite in the presence of an organic acid and lead dissolution from the lead- and organic-acid-sorbed apatite by such organic acid exposure. The lead sorption test showed that the amount of lead removed by apatite in the presence of organic acid varied depending on the type of acid used. The molar amounts of calcium dissolved from apatite in the presence and absence of organic acid were exactly the same as those of lead removed even under different pH conditions as well as different organic acid concentrations, indicating that the varying amount of lead removal in the presence of different organic acids resulted from the magnitude of the dissolution of apatite and the precipitation of lead phosphate minerals. The percentages of lead dissolved from the organic-acid-sorbed and non-organic-acid-sorbed apatite by all the organic acid extractions were equal and higher than those by water extraction. In particular, the highest extractions were observed in the non-organic-acid-sorbed apatite by citric and malic acids. These results suggest that to immobilize lead by the use of apatite in the presence of organic acids, much more apatite must be added than in the absence of organic acid, and that measures must be taken to ensure that the immobilized lead is not dissolved.
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Kulik, Tomasz; Stuper-Szablewska, Kinga; Bilska, Katarzyna; Buśko, Maciej; Ostrowska-Kołodziejczak, Anna; Załuski, Dariusz; Perkowski, Juliusz
2017-01-01
Plant-derived compounds limiting mycotoxin contamination are currently of major interest in food and feed production. However, their potential application requires an evaluation of their effects on fungal secondary metabolism and membrane effects. In this study, different strains of Fusarium culmorum and F. graminearum sensu stricto were exposed to trans-cinnamic and chlorogenic acids on solid YES media. Fusaria produced phenolic acids, whose accumulation was lowered by exogenous phenolic compounds. In addition, fungi reduced exogenous phenolic acids, leading either to their conversion or degradation. trans-Cinnamic acid was converted to caffeic and ferulic acids, while chlorogenic acid was degraded to caffeic acid. The latter underwent further degradation to protocatechuic acid. Fungal-derived trans-cinnamic acid, as the first intermediate of the shikimate pathway, increased after chlorogenic acid treatment, presumably due to the further inhibition of the conversion of trans-cinnamic acid. Exogenous trans-cinnamic and chlorogenic acid displayed the inhibition of mycotoxin production by Fusaria, which appeared to be largely dependent on the phenolic compound and its concentration and the assayed strain. Exogenous phenolic acids showed different effects on ergosterol biosynthesis by fungi. It was found that the production of this membrane sterol was stimulated by trans-cinnamic acid, while chlorogenic acid negatively impacted ergosterol biosynthesis, suggesting that phenolic acids with stronger antifungal activities may upregulate ergosterol biosynthesis by Fusaria. This paper reports on the production of phenolic acids by Fusaria for the first time. PMID:28640190
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Kulik, Tomasz; Stuper-Szablewska, Kinga; Bilska, Katarzyna; Buśko, Maciej; Ostrowska-Kołodziejczak, Anna; Załuski, Dariusz; Perkowski, Juliusz
2017-06-22
Plant-derived compounds limiting mycotoxin contamination are currently of major interest in food and feed production. However, their potential application requires an evaluation of their effects on fungal secondary metabolism and membrane effects. In this study, different strains of Fusarium culmorum and F. graminearum sensu stricto were exposed to trans -cinnamic and chlorogenic acids on solid YES media. Fusaria produced phenolic acids, whose accumulation was lowered by exogenous phenolic compounds. In addition, fungi reduced exogenous phenolic acids, leading either to their conversion or degradation. trans -Cinnamic acid was converted to caffeic and ferulic acids, while chlorogenic acid was degraded to caffeic acid. The latter underwent further degradation to protocatechuic acid. Fungal-derived trans -cinnamic acid, as the first intermediate of the shikimate pathway, increased after chlorogenic acid treatment, presumably due to the further inhibition of the conversion of trans -cinnamic acid. Exogenous trans -cinnamic and chlorogenic acid displayed the inhibition of mycotoxin production by Fusaria, which appeared to be largely dependent on the phenolic compound and its concentration and the assayed strain. Exogenous phenolic acids showed different effects on ergosterol biosynthesis by fungi. It was found that the production of this membrane sterol was stimulated by trans -cinnamic acid, while chlorogenic acid negatively impacted ergosterol biosynthesis, suggesting that phenolic acids with stronger antifungal activities may upregulate ergosterol biosynthesis by Fusaria. This paper reports on the production of phenolic acids by Fusaria for the first time.
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Locating the binding sites of folic acid with milk α- and β-caseins.
Bourassa, P; Tajmir-Riahi, H A
2012-01-12
We located the binding sites of folic acid with milk α- and β-caseins at physiological conditions, using constant protein concentration and various folic acid contents. FTIR, UV-visible, and fluorescence spectroscopic methods as well as molecular modeling were used to analyze folic acid binding sites, the binding constant, and the effect of folic acid interaction on the stability and conformation of caseins. Structural analysis showed that folic acid binds caseins via both hydrophilic and hydrophobic contacts with overall binding constants of K(folic acid-α-caseins) = 4.8 (±0.6) × 10(4) M(-1) and K(folic acid-β-caseins) = 7.0 (±0.9) × 10(4) M(-1). The number of bound acid molecules per protein was 1.5 (±0.4) for α-casein and 1.4 (±0.3) for β-casein complexes. Molecular modeling showed different binding sites for folic acid on α- and β-caseins. The participation of several amino acids in folic acid-protein complexes was observed, which was stabilized by hydrogen bonding network and the free binding energy of -7.7 kcal/mol (acid-α-casein) and -8.1 kcal/mol (acid-β-casein). Folic acid complexation altered protein secondary structure by the reduction of α-helix from 35% (free α-casein) to 33% (acid-complex) and 32% (free β-casein) to 26% (acid-complex) indicating a partial protein destabilization. Caseins might act as carriers for transportation of folic acid to target molecules.
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[Lipid synthesis by an acidic acid tolerant Rhodotorula glutinis].
Lin, Zhangnan; Liu, Hongjuan; Zhang, Jian'an; Wang, Gehua
2016-03-01
Acetic acid, as a main by-product generated in the pretreatment process of lignocellulose hydrolysis, significantly affects cell growth and lipid synthesis of oleaginous microorganisms. Therefore, we studied the tolerance of Rhodotorula glutinis to acetic acid and its lipid synthesis from substrate containing acetic acid. In the mixed sugar medium containing 6 g/L glucose and 44 g/L xylose, and supplemented with acetic acid, the cell growth was not:inhibited when the acetic acid concentration was below 10 g/L. Compared with the control, the biomass, lipid concentration and lipid content of R. glutinis increased 21.5%, 171% and 122% respectively when acetic acid concentration was 10 g/L. Furthermore, R. glutinis could accumulate lipid with acetate as the sole carbon source. Lipid concentration and lipid yield reached 3.20 g/L and 13% respectively with the initial acetic acid concentration of 25 g/L. The lipid composition was analyzed by gas chromatograph. The main composition of lipid produced with acetic acid was palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid, including 40.9% saturated fatty acids and 59.1% unsaturated fatty acids. The lipid composition was similar to that of plant oil, indicating that lipid from oleaginous yeast R. glutinis had potential as the feedstock of biodiesel production. These results demonstrated that a certain concentration of acetic acid need not to be removed in the detoxification process when using lignocelluloses hydrolysate to produce microbial lipid by R. glutinis.
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Fatty acid synthesis in Escherichia coli
Knivett, V. A.; Cullen, Julia
1967-01-01
1. Fatty acid formation by cells of a strain of Escherichia coli has been studied in the exponential, post-exponential and stationary phases of growth. 2. During the exponential phase of growth, the metabolic quotient (mμmoles of fatty acid synthesized/mg. dry wt. of cells/hr.) for each fatty acid in the extractable lipid was constant. 3. The newly synthesized fatty acid mixtures produced during this phase contained hexadecanoic acid (41%), hexadecenoic acid (31%), octadecenoic acid (21%) and the C17-cyclopropane acid, methylenehexadecanoic acid (4%). 4. As the proportion of newly synthesized material increased, changes in the fatty acid composition of the cells during this period were towards this constant composition. 5. Abrupt changes in fatty acid synthesis occurred when exponential growth ceased. 6. In media in which glycerol, or SO42− or Mg2+, was growth-limiting there was a small accumulation of C17-cyclopropane acid in cells growing in the post-exponential phase of growth. 7. Where either NH4+ or PO43− was growth-limiting and there were adequate supplies of glycerol, Mg2+ and SO42−, there was a marked accumulation of C17-cyclopropane acid and C19-cyclopropane acid appeared. 8. Under appropriate conditions the metabolic quotient for C17-cyclopropane acid increased up to sevenfold at the end of exponential growth. Simultaneously the metabolic quotients of the other acids fell. 9. A mixture of glycerol, Mg2+ and SO42− stimulated cyclopropane acid formation in resting cells. PMID:5340364
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Zhou, Yan; Ruan, Zheng; Wen, Yanmei; Yang, Yuhui; Mi, Shumei; Zhou, Lili; Wu, Xin; Ding, Sheng; Deng, Zeyuan; Wu, Guoyao; Yin, Yulong
2016-03-01
Chlorogenic acid as a natural hydroxycinnamic acid has protective effect for liver. Endotoxin induced metabolic disorder, such as lipid dysregulation and hyperlipidemia. In this study, we investigated the effect of chlorogenic acid in rats with chronic endotoxin infusion. The Sprague-Dawley rats with lipid metabolic disorder (LD group) were intraperitoneally injected endotoxin. And the rats of chlorogenic acid-LD group were daily received chlorogenic acid by intragastric administration. In chlorogenic acid-LD group, the area of visceral adipocyte was decreased and liver injury was ameliorated, as compared to LD group. In chlorogenic acid-LD group, serum triglycerides, free fatty acids, hepatic triglycerides and cholesterol were decreased, the proportion of C20:1, C24:1 and C18:3n-6, Δ9-18 and Δ6-desaturase activity index in the liver were decreased, and the proportion of C18:3n-3 acid was increased, compared to the LD group. Moreover, levels of phosphorylated AMP-activated protein kinase, carnitine palmitoyltransferase-I, and fatty acid β-oxidation were increased in chlorogenic acid-LD group compared to LD rats, whereas levels of fatty acid synthase and acetyl-CoA carboxylase were decreased. These findings demonstrate that chlorogenic acid effectively improves hepatic lipid dysregulation in rats by regulating fatty acid metabolism enzymes, stimulating AMP-activated protein kinase activation, and modulating levels of hepatic fatty acids.
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Hemalatha, G. R.; Rao, D. Satyanarayana; Guruprasad, L.
2007-01-01
We have identified four repeats and ten domains that are novel in proteins encoded by the Bacillus anthracis str. Ames proteome using automated in silico methods. A “repeat” corresponds to a region comprising less than 55-amino-acid residues that occur more than once in the protein sequence and sometimes present in tandem. A “domain” corresponds to a conserved region with greater than 55-amino-acid residues and may be present as single or multiple copies in the protein sequence. These correspond to (1) 57-amino-acid-residue PxV domain, (2) 122-amino-acid-residue FxF domain, (3) 111-amino-acid-residue YEFF domain, (4) 109-amino-acid-residue IMxxH domain, (5) 103-amino-acid-residue VxxT domain, (6) 84-amino-acid-residue ExW domain, (7) 104-amino-acid-residue NTGFIG domain, (8) 36-amino-acid-residue NxGK repeat, (9) 95-amino-acid-residue VYV domain, (10) 75-amino-acid-residue KEWE domain, (11) 59-amino-acid-residue AFL domain, (12) 53-amino-acid-residue RIDVK repeat, (13) (a) 41-amino-acid-residue AGQF repeat and (b) 42-amino-acid-residue GSAL repeat. A repeat or domain type is characterized by specific conserved sequence motifs. We discuss the presence of these repeats and domains in proteins from other genomes and their probable secondary structure. PMID:17538688
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el-Ziney, M G; De Meyer, H; Debevere, J M
1997-03-03
The influence of different organic acids (lactic, acetic, formic and propionic acids) at equimolar concentrations of undissociated acid with pH range of 3.9, 5.8, on the aerobic and anaerobic growth and survival kinetics of the virulent strain of Y. enterocolitica IP 383 0:9, was determined in tryptone soy broth at 4 degrees C. Growth and survival data were analyzed and fitted by a modification of the Whiting and Cygnarowicz-Provost model, using the Minpack software library. Initial generation times, initial specific growth rates, lag time and dead rate were subsequently calculated from the model parameters. The results demonstrate that the inhibitory effects of the acids were divided into two categories dependent upon pH. At high pH (5.8) the order of inhibition was formic acid > acetic acid > propionic acid > lactic acid, whereas at lower pH it became formic acid > lactic acid > acetic acid > propionic acid. The inhibitory effect of lactic acid is enhanced under anaerobic condition. Nevertheless, when the organism was cultured anaerobically, it was shown to be more tolerant to formic and acetic acids. Moreover, these variables (type of organic acid, pH and atmosphere) did not lead to the loss of the virulence plasmid in growing and surviving cells. The mechanism of inhibitory effect for each of the acids are also discussed.
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Variability in coconut (Cocos nucifera L.) germplasm and hybrids for fatty acid profile of oil.
Kumar, S Naresh
2011-12-28
Coconut oil, the main product of coconut fruit, is the richest source of glycerol and lauric acid and hence is called lauric oil. This paper reports the fatty acid profile of oil from 60 Talls, 14 Dwarfs, and 34 hybrids. These include collections from 13 countries covering a large coconut-growing area of the world, apart from the indigenous ones. Capillary gas chromatography analysis of oil indicated a wider variation for the fatty acid profile than earlier reported. Apart from this, for the first time other fatty acids such as behenic and lignoceric acids were detected. Oil from cultivars and hybrids of coconut has significantly differed, particularly for commercially important fatty acids such as lauric acid and unsaturated fatty acids. However, coconut oil seems to have a conserved fatty acid profile, mainly because of low unsaturated fatty acids, indicating the possibility of grouping cultivars on the basis of their fatty acid profiles. The cluster analysis based on fatty acid profile indicated grouping together of geographically and typically closely related cultivars. Cultivars with high concentrations of specific fatty acids can be of potential use for industrial exploitation, whereas those with high concentrations of short- and medium-chain fatty acids and unsaturated fatty acids are more suitable for human consumption. Cultivars and hybrids with high and low values for each of the fatty acids are also identified.
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Qin, Xiaopeng; Liu, Fei; Wang, Guangcai; Weng, Liping
2012-12-01
An accurate and fast method for simultaneous determination of small organic acids and much larger humic acids was developed using high performance size exclusion chromatography. Two small organic acids, i.e. salicylic acid and 2,3-dihydroxybenzoic acid, and one purified humic acid material were used in this study. Under the experimental conditions, the UV peaks of salicylic acid and 2,3-dihydroxybenzoic acid were well separated from the peaks of humic acid in the chromatogram. Concentrations of the two small organic acids could be accurately determined from their peak areas. The concentration of humic acid in the mixture could then be derived from mass balance calculations. The measured results agreed well with the nominal concentrations. The detection limits are 0.05 mg/L and 0.01 mg/L for salicylic acid and 2,3-dihydroxybenzoic acid, respectively. Applicability of the method to natural samples was tested using groundwater, glacier, and river water samples (both original and spiked with salicylic acid and 2,3-dihydroxybenzoic acid) with a total organic carbon concentration ranging from 2.1 to 179.5 mg C/L. The results obtained are promising, especially for groundwater samples and river water samples with a total organic carbon concentration below 9 mg C/L. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Cocrystallization out of the blue: DL-mandelic acid/ethyl-DL-mandelate cocrystal
NASA Astrophysics Data System (ADS)
Tumanova, Natalia; Payen, Ricky; Springuel, Géraldine; Norberg, Bernadette; Robeyns, Koen; Le Duff, Cécile; Wouters, Johan; Leyssens, Tom
2017-01-01
This work focuses on a peculiar behavior of racemic mandelic acid in ethanol solution. Dissolution of racemic mandelic acid in ethanol followed by evaporation to dryness results in a DL-mandelic acid/ethyl-DL-mandelate cocrystal. This behavior indicates that racemic mandelic acid tends not only to transform into an ester in ethanol, but also to cocrystallize with untransformed acid molecules. Cocrystal formation for mandelic acid in ethanol was found to be reproducible under various conditions. DL-tropic acid and DL-phenyllactic acid that contain similar functional groups and that were tested as well, on the other hand, showed no cocrystal formation: DL-phenyllactic acid partly converted into an ester, whereas DL-tropic acid mostly recrystallized.
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[Study on anti-bacterium activity of ginkgolic acids and their momomers].
Yang, Xiaoming; Zhu, Wei; Chen, Jun; Qian, Zhiyu; Xie, Jimin
2004-09-01
Ginkgolic acids and their three monomers were separated from ginkgo sarcotestas. The anti-bacterium activity of ginkgolic acids were tested. The relation between the anti-bacterium activity and side chain of ginkgolic acid were studied. The MIC of ginkgolic acids and their three monomers and salicylic acid were tested. Ginkgolic acid has strong inhibitive effect on G+-bacterium. Salicylic acid has no side chain, so no anti-bacterial activity. When the length of gingkolic acid side chain is C13:0, it has the strongest anti-bacterial activity in three monomers. The side chain of ginkgolic acid is the key functional group that possessed anti-bacterial activity. The length of Ginkgolic acid was the main effective factor of anti-bacterial activity.
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In vitro enzymic hydrolysis of chlorogenic acids in coffee.
da Encarnação, Joana Amarante; Farrell, Tracy L; Ryder, Alexandra; Kraut, Nicolai U; Williamson, Gary
2015-02-01
Coffee is rich in quinic acid esters of phenolic acids (chlorogenic acids) but also contains some free phenolic acids. A proportion of phenolic acids appear in the blood rapidly after coffee consumption due to absorption in the small intestine. We investigated in vitro whether this appearance could potentially be derived from free phenolic acids in instant coffee or from hydrolysis of chlorogenic acids by pancreatic or brush border enzymes. We quantified six free phenolic acids in instant coffees using HPLC-DAD-mass spectrometry. The highest was caffeic acid, but all were present at low levels compared to the chlorogenic acids. Roasting and decaffeination significantly reduced free phenolic acid content. We estimated, using pharmacokinetic modelling with previously published data, that the contribution of these compounds to small intestinal absorption is minimal. Hydrolysis of certain chlorogenic acids was observed with human-differentiated Caco-2 cell monolayers and with porcine pancreatin, which showed maximal rates on 3- and 5-O-caffeoylquinic acids, respectively. The amounts of certain free phenolic acids in coffee could only minimally account for small intestinal absorption based on modelling. The hydrolysis of caffeoylquinic, but not feruloylquinic acids, by enterocyte and pancreatic esterases is potentially a contributing mechanism to small intestinal absorption. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Jaiswal, Rakesh; Kuhnert, Nikolai
2011-04-27
Arnica montana is a medicinally important plant due to its broad health effects, and it is used in Ayurvedic, Homeopathic, Unani, and folk medicines. We have used LC-MS(n) (n = 2-5) to detect and characterize in Arnica flowers 11 quantitatively minor fumaric and methoxyoxalic acid-containing chlorogenic acids, nine of them not previously reported in nature. These comprise 1,5-dicaffeoyl-3-methoxyoxaloylquinic acid, 1,3-dicaffeoyl-4-methoxyoxaloylquinic acid, 3,5-dicaffeoyl-4-methoxyoxaloylquinic acid, and 1-methoxyoxaloyl-4,5-dicaffeoylquinic acid (M(r) 602); 3-caffeoyl-4-feruloyl-5-methoxyoxaloylquinic acid and 3-feruloyl-4-methoxyoxaloyl-5-caffeoylquinic acid (M(r) 616); 1,5-dicaffeoyl-4-fumaroyl and 1,5-dicaffeoyl-3-fumaroylquinic acid (M(r) 614); 3,5-dicaffeoyl-1,4-dimethoxyoxaloylquinic acid (M(r) 688); and 1-methoxyoxaloyl-3,4,5-tricaffeoylquinic acid and 1,3,4-tricaffeoyl-5-methoxyoxaloylquinic acid (M(r) 764). All of the structures have been assigned on the basis of LC-MS(n) patterns of fragmentation, relative hydrophobicity, and analogy of fragmentation patterns if compared to caffeoylquinic acids. This is the first time when fumaric acid-containing chlorogenic acids are reported in nature.
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A Glutamic Acid-Producing Lactic Acid Bacteria Isolated from Malaysian Fermented Foods
Zareian, Mohsen; Ebrahimpour, Afshin; Bakar, Fatimah Abu; Mohamed, Abdul Karim Sabo; Forghani, Bita; Ab-Kadir, Mohd Safuan B.; Saari, Nazamid
2012-01-01
l-glutamaic acid is the principal excitatory neurotransmitter in the brain and an important intermediate in metabolism. In the present study, lactic acid bacteria (218) were isolated from six different fermented foods as potent sources of glutamic acid producers. The presumptive bacteria were tested for their ability to synthesize glutamic acid. Out of the 35 strains showing this capability, strain MNZ was determined as the highest glutamic-acid producer. Identification tests including 16S rRNA gene sequencing and sugar assimilation ability identified the strain MNZ as Lactobacillus plantarum. The characteristics of this microorganism related to its glutamic acid-producing ability, growth rate, glucose consumption and pH profile were studied. Results revealed that glutamic acid was formed inside the cell and excreted into the extracellular medium. Glutamic acid production was found to be growth-associated and glucose significantly enhanced glutamic acid production (1.032 mmol/L) compared to other carbon sources. A concentration of 0.7% ammonium nitrate as a nitrogen source effectively enhanced glutamic acid production. To the best of our knowledge this is the first report of glutamic acid production by lactic acid bacteria. The results of this study can be further applied for developing functional foods enriched in glutamic acid and subsequently γ-amino butyric acid (GABA) as a bioactive compound. PMID:22754309
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Benyo, B; Biro, J C; Benyo, Z
2004-01-01
The theory of "codon-amino acid coevolution" was first proposed by Woese in 1967. It suggests that there is a stereochemical matching - that is, affinity - between amino acids and certain of the base triplet sequences that code for those amino acids. We have constructed a common periodic table of codons and amino acids, where the nucleic acid table showed perfect axial symmetry for codons and the corresponding amino acid table also displayed periodicity regarding the biochemical properties (charge and hydrophobicity) of the 20 amino acids and the position of the stop signals. The table indicates that the middle (2/sup nd/) amino acid in the codon has a prominent role in determining some of the structural features of the amino acids. The possibility that physical contact between codons and amino acids might exist was tested on restriction enzymes. Many recognition site-like sequences were found in the coding sequences of these enzymes and as many as 73 examples of codon-amino acid co-location were observed in the 7 known 3D structures (December 2003) of endonuclease-nucleic acid complexes. These results indicate that the smallest possible units of specific nucleic acid-protein interaction are indeed the stereochemically compatible codons and amino acids.
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Liu, Feng-xia; Xue, Gang; Gao, Qiu-hua; Gao, Wei-xia; Zhang, Li-hua
2005-03-01
To measure the saponification value and fatty acid formation of evening primrose oil, to study the effects of pH value on production yield and fatty acid formation during the saponification reaction, and to provide rationales for the selection of raw material, the enhancement of production yield of saponification, and the encapsulation of gamma-linolenic acid with urea. To measure fatty acid's formation with gas chromatographic method and to measure the saponification value. The content of gamma-linolenic acid is 7%-10% in evening primrose oil. The content of gamma-linolenic acid is inversely correlated with that of unsaturated fatty acid. The saponification value, the amount of KOH for saponification of evening primrose oil, and the pH value for subsequent isolations of oils are determined. From the measurement of fatty acids of evening primrose oil in two different cultivation locations, the content of gamma-linolenic acid is determined to be 7%-10%, unsaturated oils account for 90%. The saponification value of evening primrose oil is between 180-200, pH value of isolated oil is 1.5-2.0 after saponification reaction. Fatty acids mainly include palmitic acid, stearic acid, oleic acid, linolic acid and gamma-linolenic acid.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Goto, Tsuyoshi, E-mail: tgoto@kais.kyoto-u.ac.jp; Research Unit for Physiological Chemistry, The Center for the Promotion of Interdisciplinary Education and Research, Kyoto University; Kim, Young-Il
2015-04-17
Our previous study has shown that gut lactic acid bacteria generate various kinds of fatty acids from polyunsaturated fatty acids such as linoleic acid (LA). In this study, we investigated the effects of LA and LA-derived fatty acids on the activation of peroxisome proliferator-activated receptors (PPARs) which regulate whole-body energy metabolism. None of the fatty acids activated PPARδ, whereas almost all activated PPARα in luciferase assays. Two fatty acids potently activated PPARγ, a master regulator of adipocyte differentiation, with 10-oxo-12(Z)-octadecenoic acid (KetoA) having the most potency. In 3T3-L1 cells, KetoA induced adipocyte differentiation via the activation of PPARγ, and increasedmore » adiponectin production and insulin-stimulated glucose uptake. These findings suggest that fatty acids, including KetoA, generated in gut by lactic acid bacteria may be involved in the regulation of host energy metabolism. - Highlights: • Most LA-derived fatty acids from gut lactic acid bacteria potently activated PPARα. • Among tested fatty acids, KetoA and KetoC significantly activated PPARγ. • KetoA induced adipocyte differentiation via the activation of PPARγ. • KetoA enhanced adiponectin production and glucose uptake during adipogenesis.« less
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Incorporation of Oxygen into Abscisic Acid and Phaseic Acid from Molecular Oxygen 1
Creelman, Robert A.; Zeevaart, Jan A. D.
1984-01-01
Abscisic acid accumulates in detached, wilted leaves of Xanthium strumarium. When these leaves are subsequently rehydrated, phaseic acid, a catabolite of abscisic acid, accumulates. Analysis by gas chromatography-mass spectrometry of phaseic acid isolated from stressed and subsequently rehydrated leaves placed in an atmosphere containing 20% 18O2 and 80% N2 indicates that one atom of 18O is incorporated in the 6′-hydroxymethyl group of phaseic acid. This suggests that the enzyme that converts abscisic acid to phaseic acid is an oxygenase. Analysis by gas chromatography-mass spectrometry of abscisic acid isolated from stressed leaves kept in an atmosphere containing 18O2 indicates that one atom of 18O is present in the carboxyl group of abscisic acid. Thus, when abscisic acid accumulates in water-stressed leaves, only one of the four oxygens present in the abscisic acid molecule is derived from molecular oxygen. This suggests that either (a) the oxygen present in the 1′-, 4′-, and one of the two oxygens at the 1-position of abscisic acid arise from water, or (b) there exists a stored precursor with oxygen atoms already present in the 1′- and 4′-positions of abscisic acid which is converted to abscisic acid under conditions of water stress. PMID:16663564
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Incorporation of oxygen into abscisic Acid and phaseic Acid from molecular oxygen.
Creelman, R A; Zeevaart, J A
1984-05-01
Abscisic acid accumulates in detached, wilted leaves of Xanthium strumarium. When these leaves are subsequently rehydrated, phaseic acid, a catabolite of abscisic acid, accumulates. Analysis by gas chromatography-mass spectrometry of phaseic acid isolated from stressed and subsequently rehydrated leaves placed in an atmosphere containing 20% (18)O(2) and 80% N(2) indicates that one atom of (18)O is incorporated in the 6'-hydroxymethyl group of phaseic acid. This suggests that the enzyme that converts abscisic acid to phaseic acid is an oxygenase.Analysis by gas chromatography-mass spectrometry of abscisic acid isolated from stressed leaves kept in an atmosphere containing (18)O(2) indicates that one atom of (18)O is present in the carboxyl group of abscisic acid. Thus, when abscisic acid accumulates in water-stressed leaves, only one of the four oxygens present in the abscisic acid molecule is derived from molecular oxygen. This suggests that either (a) the oxygen present in the 1'-, 4'-, and one of the two oxygens at the 1-position of abscisic acid arise from water, or (b) there exists a stored precursor with oxygen atoms already present in the 1'- and 4'-positions of abscisic acid which is converted to abscisic acid under conditions of water stress.
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Xu, Jian; Chen, Yang-Qiu; Zhang, Hong-Jian; Tang, Lei; Wang, Ke; Zhang, Jian-Hua; Chen, Xu-Sheng; Mao, Zhong-Gui
2014-09-01
An integrated citric acid-methane fermentation process was proposed to solve the problem of extraction wastewater in citric acid fermentation process. Extraction wastewater was treated by anaerobic digestion and then recycled for the next batch of citric acid fermentation to eliminate wastewater discharge and reduce water resource consumption. Acetic acid as an intermediate product of methane fermentation was present in anaerobic digestion effluent. In this study, the effect of acetic acid on citric acid fermentation was investigated and results showed that lower concentration of acetic acid could promote Aspergillus niger growth and citric acid production. 5-Cyano-2,3-ditolyl tetrazolium chloride (CTC) staining was used to quantify the activity of A. niger cells, and the results suggested that when acetic acid concentration was above 8 mM at initial pH 4.5, the morphology of A. niger became uneven and the part of the cells' activity was significantly reduced, thereby resulting in deceasing of citric acid production. Effects of acetic acid on citric acid fermentation, as influenced by initial pH and cell number in inocula, were also examined. The result indicated that inhibition by acetic acid increased as initial pH declined and was rarely influenced by cell number in inocula.
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Method for isolating chromosomal DNA in preparation for hybridization in suspension
Lucas, Joe N.
2000-01-01
A method is provided for detecting nucleic acid sequence aberrations using two immobilization steps. According to the method, a nucleic acid sequence aberration is detected by detecting nucleic acid sequences having both a first nucleic acid sequence type (e.g., from a first chromosome) and a second nucleic acid sequence type (e.g., from a second chromosome), the presence of the first and the second nucleic acid sequence type on the same nucleic acid sequence indicating the presence of a nucleic acid sequence aberration. In the method, immobilization of a first hybridization probe is used to isolate a first set of nucleic acids in the sample which contain the first nucleic acid sequence type. Immobilization of a second hybridization probe is then used to isolate a second set of nucleic acids from within the first set of nucleic acids which contain the second nucleic acid sequence type. The second set of nucleic acids are then detected, their presence indicating the presence of a nucleic acid sequence aberration. Chromosomal DNA in a sample containing cell debris is prepared for hybridization in suspension by treating the mixture with RNase. The treated DNA can also be fixed prior to hybridization.
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Szabó, Eva; Boehm, Günther; Beermann, Christopher; Weyermann, Maria; Brenner, Hermann; Rothenbacher, Dietrich; Decsi, Tamás
2007-05-01
Several observational studies indicate that trans isomeric fatty acids may interfere with the metabolism of essential fatty acids in the human organism. The objective was to investigate the relation between trans fatty acids and long-chain polyunsaturates in mature human milk. Human milk samples (n=769) were obtained at the 6th week of lactation from mothers participating in a birth cohort study in Germany. The fatty acid composition of the milk samples was measured by high-resolution capillary gas-liquid chromatography. trans Octadecenoic and trans octadecadienoic acids were inversely correlated with linoleic acid (r=-0.32 and -0.33, P<0.0001 for both), alpha-linolenic acid (r=-0.35 and -0.27, P<0.0001), arachidonic acid (r=-0.60 and -0.47, P<0.0001), and docosahexaenoic acid (r=-0.51 and -0.33, P<0.0001). In contrast, no inverse correlations were observed between trans hexadecenoic acid and polyunsaturated fatty acids. The data obtained in the present study suggest that the availability of 18-carbon trans isomeric fatty acids may be inversely related to the availability of long-chain polyunsaturated fatty acids in mature human milk.
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Ma, Wenjie; Wu, Jason H Y; Wang, Qianyi; Lemaitre, Rozenn N; Mukamal, Kenneth J; Djoussé, Luc; King, Irena B; Song, Xiaoling; Biggs, Mary L; Delaney, Joseph A; Kizer, Jorge R; Siscovick, David S; Mozaffarian, Dariush
2015-01-01
Experimental evidence suggests that hepatic de novo lipogenesis (DNL) affects insulin homeostasis via synthesis of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). Few prospective studies have used fatty acid biomarkers to assess associations with type 2 diabetes. We investigated associations of major circulating SFAs [palmitic acid (16:0) and stearic acid (18:0)] and MUFA [oleic acid (18:1n-9)] in the DNL pathway with metabolic risk factors and incident diabetes in community-based older U.S. adults in the Cardiovascular Health Study. We secondarily assessed other DNL fatty acid biomarkers [myristic acid (14:0), palmitoleic acid (16:1n-7), 7-hexadecenoic acid (16:1n-9), and vaccenic acid (18:1n-7)] and estimated dietary SFAs and MUFAs. In 3004 participants free of diabetes, plasma phospholipid fatty acids were measured in 1992, and incident diabetes was identified by medication use and blood glucose. Usual diets were assessed by using repeated food-frequency questionnaires. Multivariable linear and Cox regression were used to assess associations with metabolic risk factors and incident diabetes, respectively. At baseline, circulating palmitic acid and stearic acid were positively associated with adiposity, triglycerides, inflammation biomarkers, and insulin resistance (P-trend < 0.01 each), whereas oleic acid showed generally beneficial associations (P-trend < 0.001 each). During 30,763 person-years, 297 incident diabetes cases occurred. With adjustment for demographics and lifestyle, palmitic acid (extreme-quintile HR: 1.89; 95% CI: 1.27, 2.83; P-trend = 0.001) and stearic acid (HR: 1.62; 95% CI: 1.09, 2.41; P-trend = 0.006) were associated with higher diabetes risk, whereas oleic acid was not significantly associated. In secondary analyses, vaccenic acid was inversely associated with diabetes (HR: 0.56; 95% CI: 0.38, 0.83; P-trend = 0.005). Other fatty acid biomarkers and estimated dietary SFAs or MUFAs were not significantly associated with incident diabetes. In this large prospective cohort, circulating palmitic acid and stearic acid were associated with higher diabetes risk, and vaccenic acid was associated with lower diabetes risk. These results indicate a need for additional investigation of biological mechanisms linking specific fatty acids in the DNL pathway to the pathogenesis of diabetes. © 2015 American Society for Nutrition.
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Wu, Jason HY; Wang, Qianyi; Lemaitre, Rozenn N; Mukamal, Kenneth J; Djoussé, Luc; King, Irena B; Song, Xiaoling; Biggs, Mary L; Delaney, Joseph A; Kizer, Jorge R; Siscovick, David S; Mozaffarian, Dariush
2015-01-01
Background: Experimental evidence suggests that hepatic de novo lipogenesis (DNL) affects insulin homeostasis via synthesis of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). Few prospective studies have used fatty acid biomarkers to assess associations with type 2 diabetes. Objectives: We investigated associations of major circulating SFAs [palmitic acid (16:0) and stearic acid (18:0)] and MUFA [oleic acid (18:1n–9)] in the DNL pathway with metabolic risk factors and incident diabetes in community-based older U.S. adults in the Cardiovascular Health Study. We secondarily assessed other DNL fatty acid biomarkers [myristic acid (14:0), palmitoleic acid (16:1n–7), 7-hexadecenoic acid (16:1n–9), and vaccenic acid (18:1n–7)] and estimated dietary SFAs and MUFAs. Design: In 3004 participants free of diabetes, plasma phospholipid fatty acids were measured in 1992, and incident diabetes was identified by medication use and blood glucose. Usual diets were assessed by using repeated food-frequency questionnaires. Multivariable linear and Cox regression were used to assess associations with metabolic risk factors and incident diabetes, respectively. Results: At baseline, circulating palmitic acid and stearic acid were positively associated with adiposity, triglycerides, inflammation biomarkers, and insulin resistance (P-trend < 0.01 each), whereas oleic acid showed generally beneficial associations (P-trend < 0.001 each). During 30,763 person-years, 297 incident diabetes cases occurred. With adjustment for demographics and lifestyle, palmitic acid (extreme-quintile HR: 1.89; 95% CI: 1.27, 2.83; P-trend = 0.001) and stearic acid (HR: 1.62; 95% CI: 1.09, 2.41; P-trend = 0.006) were associated with higher diabetes risk, whereas oleic acid was not significantly associated. In secondary analyses, vaccenic acid was inversely associated with diabetes (HR: 0.56; 95% CI: 0.38, 0.83; P-trend = 0.005). Other fatty acid biomarkers and estimated dietary SFAs or MUFAs were not significantly associated with incident diabetes. Conclusions: In this large prospective cohort, circulating palmitic acid and stearic acid were associated with higher diabetes risk, and vaccenic acid was associated with lower diabetes risk. These results indicate a need for additional investigation of biological mechanisms linking specific fatty acids in the DNL pathway to the pathogenesis of diabetes. This trial was registered at clinicaltrials.gov as NCT00005133. PMID:25527759
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21 CFR 184.1328 - Glyceryl behenate.
Code of Federal Regulations, 2010 CFR
2010-04-01
... glyceryl esters of behenic acid made from glycerin and behenic acid (a saturated C22 fatty acid). The... not more than 2.5 percent free fatty acids. (2) Behenic acid. Between 80 and 90 percent of the total fatty acid content. (3) Acid value. Not more than 4. (4) Saponification value. Between 145 and 165. (5...
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21 CFR 862.1450 - Lactic acid test system.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Lactic acid test system. 862.1450 Section 862.1450....1450 Lactic acid test system. (a) Identification. A lactic acid test system is a device intended to measure lactic acid in whole blood and plasma. Lactic acid measurements that evaluate the acid-base status...
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21 CFR 862.1450 - Lactic acid test system.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Lactic acid test system. 862.1450 Section 862.1450....1450 Lactic acid test system. (a) Identification. A lactic acid test system is a device intended to measure lactic acid in whole blood and plasma. Lactic acid measurements that evaluate the acid-base status...
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21 CFR 862.1450 - Lactic acid test system.
Code of Federal Regulations, 2012 CFR
2012-04-01
... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Lactic acid test system. 862.1450 Section 862.1450....1450 Lactic acid test system. (a) Identification. A lactic acid test system is a device intended to measure lactic acid in whole blood and plasma. Lactic acid measurements that evaluate the acid-base status...
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21 CFR 862.1450 - Lactic acid test system.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lactic acid test system. 862.1450 Section 862.1450....1450 Lactic acid test system. (a) Identification. A lactic acid test system is a device intended to measure lactic acid in whole blood and plasma. Lactic acid measurements that evaluate the acid-base status...
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21 CFR 184.1328 - Glyceryl behenate.
Code of Federal Regulations, 2011 CFR
2011-04-01
... glyceryl esters of behenic acid made from glycerin and behenic acid (a saturated C22 fatty acid). The... not more than 2.5 percent free fatty acids. (2) Behenic acid. Between 80 and 90 percent of the total fatty acid content. (3) Acid value. Not more than 4. (4) Saponification value. Between 145 and 165. (5...
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OCCURRENCE OF IODO-ACID AND IODO-THM DISINFECTION BY-PRODUCTS IN CHLORAMINATED DRINKING WATER
Iodo-acids were recently identified for the first time as DBPs in drinking water disinfected with chloramines. The iodo-acids identified included iodoacetic acid (IAA), bromoiodoacetic acid, (E)-3-bromo-3-iodo-propenoic acid, (Z)-3-bromo-3-iodo-propenoic acid, and (E)-2-iodo-3...
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OCCURRENCE OF IODO-ACID AND IODO-THM DBPS IN U. S. CHLORAMINATED DRINKING WATERS
Iodo-acids were recently identified for the first time as DBPs in drinking water disinfected with chloramines. The iodo-acids identified included iodoacetic acid (IAA), bromoiodoacetic acid, (E)-3-bromo-3-iodo-propenoic acid, (Z)-3-bromo-3-iodo-propenoic acid, and (E)-2-iodo-3...
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Biogeochemistry of aquatic humic substances in Thoreau's Bog, Concord, Massachusetts
McKnight, Diane M.; Thurman, E. Michael; Wershaw, Robert L.; Hemond, Herold
1985-01-01
Thoreau's Bog is an ombrotrophic floating—mat Sphagnum bog developed in a glacial kettlehole and surrounded by a red maple swamp. Concentrations of dissolved organic carbon in the porewater of the bog average 36 mg/L and are greatest near the surface, especially during late summer. This distribution suggest that the upper layer of living and dead Sphagnum and moderately humified peat is the major site of dissolved organic material production in the bog. The dissolved organic material consists mainly of aquatic fulvic acid (67%) and hydrophilic acids (20%); these organic acids control the pH (typically 4 or somewhat lower) of the bogwater. The elemental, amino acid, carbohydrate, and carboxylic acid contents of fulvic acid from the bog are similar to those of aquatic fulvic acid from the nearby Shawsheen River, although the phenolic hydroxyl content of fulvic acid from Thoreau's Bog is higher. The hydrophilic acids have greater amino acid, carbohydrate, and carboxylic acid contents than the fulvic acid, consistent with the hypothesis that hydrophilic acids are more labile intermediate compounds in the formation of fulvic acid.
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Effect of acidity on the physicochemical properties of α- and β-chitin nanofibers.
Suenaga, Shin; Totani, Kazuhide; Nomura, Yoshihiro; Yamashita, Kazuhiko; Shimada, Iori; Fukunaga, Hiroshi; Takahashi, Nobuhide; Osada, Mitsumasa
2017-09-01
We have investigated whether acidity can be used to control the physicochemical properties of chitin nanofibers (ChNFs). In this study, we define acidity as the molar ratio of dissociated protons from the acid to the amino groups in the raw chitin powder. The effect of acidity on the physicochemical properties of α- and β-ChNFs was compared. The transmittance and viscosity of the β-ChNFs drastically and continuously increased with increasing acidity, while those of the α-ChNFs were not affected by acidity. These differences are because of the higher ability for cationization based on the more flexible crystal structure of β-chitin than α-chitin. In addition, the effect of the acid species on the transmittance of β-ChNFs was investigated. The transmittance of β-ChNFs can be expressed by the acidity regardless of the acid species, such as hydrochloric acid, phosphoric acid, and acetic acid. These results indicate that the acidity defined in this work is an effective parameter to define and control the physicochemical properties of ChNFs. Copyright © 2017 Elsevier B.V. All rights reserved.
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Effects of Phenolic Compounds on Growth of Colletotrichum spp. In Vitro.
Roy, Sutapa; Nuckles, Etta; Archbold, Douglas D
2018-05-01
Colletotrichum acutatum is responsible for anthracnose fruit rot, one of the most devastating diseases in strawberry. Phenolic compounds have been described as contributors to anthracnose resistance in strawberry (Fragaria x ananassa, Duch.). Six isolates of Colletotrichum acutatum and four isolates of three other Colletotrichum species, C. gloeosporioides, C. fragariae, and C. graminicola, associated with disease symptoms were investigated in this study. The potential inhibitory effect of phenolic acids (gallic acid, caffeic acid, chlorogenic acid, ferulic acid, trans-cinnamic acid, p-coumaric acid, salicylic acid), flavonoids (catechin, quercetin, naringenin), and ellagic acid, which are naturally found in strawberry, were screened against two different spore suspension concentrations of the Colletotrichum isolates at 5, 10, 50 mM in vitro. Among the phenolic acids and flavonoids tested in this study, only trans-cinnamic acid, ferulic acid, and p-coumaric acid inhibited fungal growth. The inhibitory effects were concentration-dependent but also varied with the spore suspension concentration of the isolates. The results demonstrated that trans-cinnamic acid had the greatest inhibitory effect on all Colletotrichum spp. isolates tested.
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Zhang, Ke; Li, Huidong; Chen, Wuxi; Zhao, Minli; Cui, Haiyang; Min, Qingsong; Wang, Haijun; Chen, Shulin; Li, Demao
2017-05-01
Docosapentaenoic acid/docosahexaenoic acid ratio (DPA/DHA ratio) in Schizochytrium was relatively stable. But ideally the ratio of DPA/DHA will vary according to the desired end use. This study reports several ways of modulating the DPA/DHA ratio. Incubation times changed the DPA/DHA ratio, and changes in this ratio were associated with the variations in the saturated fatty acid (SFAs) content. Propionic acid sharply increased the SFAs content in lipids, dramatically decreased the even-chain SFAs content, and reduced the DPA/DHA ratio. Pentanoic acid (C5:0) and heptanoic acid (C7:0) had similar effects as propionic acid, whereas butyric acid (C4:0), hexanoic acid (C6:0), and octanoic acid (C8:0) did not change the fatty acid profile and the DPA/DHA ratio. Transcription analyses show that β-oxidation might be responsible for this phenomenon. Iodoacetamide upregulated polyunsaturated fatty acid (PUFA) synthase genes, reduced the DHA content, and improved the DPA content, causing the DPA/DHA ratio to increase. These results present new insights into the regulation of the DPA/DHA ratio.
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Chen, Hengye; Virk, Muhammad Safiullah; Chen, Fusheng
2016-06-01
The concentration of advanced glycation end products (AGEs) in foods, which are formed by Maillard reaction, has demonstrated as risk factors associated with many chronic diseases. The AGEs inhibitory activities of five common phenolic acids (protocatechuic acid, dihydroferulic acid, p-coumaric acid, p-hydroxybenzoic acid and salicylic acid) with different chemical properties had been investigated in two food simulation systems (glucose-bovine serum albumin (BSA) and oleic acid-BSA). The results substantiated that the AGEs inhibitory abilities of phenolic acids in the oleic acid BSA system were much better than the glucose-BSA system for their strong reducing powers and structures. Among them, dihydrogenferulic acid showed strong inhibition of AGEs formation in oleic acid-BSA system at 0.01 mg/mL compared to nonsignificant AGEs inhibitory effect in oleic acid-BSA system at 10-fold higher concentration (0.1 mg/mL). This study suggests that edible plants rich in phenolic acids may be used as AGEs inhibitor during high-fat cooking.
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Variation of unsaturated fatty acids in soybean sprout of high oleic acid accessions.
Dhakal, Krishna Hari; Jung, Ki-Hwal; Chae, Jong-Hyun; Shannon, J Grover; Lee, Jeong-Dong
2014-12-01
Oleic acid and oleic acid rich foods may have beneficial health effects in humans. Soybeans with high oleic acid (around 80% in seed oil) have been developed. Soybean sprouts are an important vegetable in Korea, Japan and China. The objective of this study was to investigate the variation of unsaturated fatty acids, oleic, linoleic and α-linolenic acids, in sprouts from soybeans with normal and high oleic acid concentration. Twelve soybean accessions with six high oleic acid lines, three parents of high oleic acid lines, and three checks with normal and high oleic acid concentration were used in this study. The unsaturated fatty acid concentration in sprouts from each genotype was similar to the concentration in the ungerminated seed. The oleic acid concentration in the sprouts of high oleic acid lines (up to 80%) was still high (>70%) compared to the ungerminated seed. Thus, high oleic soybean varieties developed for sprout production could add valuable health benefits to sprouts and the individuals who consume this vegetable. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Spilioti, Eliana; Jaakkola, Mari; Tolonen, Tiina; Lipponen, Maija; Virtanen, Vesa; Chinou, Ioanna; Kassi, Eva; Karabournioti, Sofia; Moutsatsou, Paraskevi
2014-01-01
The phenolic acid profile of honey depends greatly on its botanical and geographical origin. In this study, we carried out a quantitative analysis of phenolic acids in the ethyl acetate extract of 12 honeys collected from various regions in Greece. Our findings indicate that protocatechuic acid, p-hydroxybenzoic acid, vanillic acid, caffeic acid and p-coumaric acid are the major phenolic acids of the honeys examined. Conifer tree honey (from pine and fir) contained significantly higher concentrations of protocatechuic and caffeic acid (mean: 6640 and 397 µg/kg honey respectively) than thyme and citrus honey (mean of protocatechuic and caffeic acid: 437.6 and 116 µg/kg honey respectively). p-Hydroxybenzoic acid was the dominant compound in thyme honeys (mean: 1252.5 µg/kg honey). We further examined the antioxidant potential (ORAC assay) of the extracts, their ability to influence viability of prostate cancer (PC-3) and breast cancer (MCF-7) cells as well as their lowering effect on TNF- α-induced adhesion molecule expression in endothelial cells (HAEC). ORAC values of Greek honeys ranged from 415 to 2129 µmol Trolox equivalent/kg honey and correlated significantly with their content in protocatechuic acid (p<0.001), p-hydroxybenzoic acid (p<0.01), vanillic acid (p<0.05), caffeic acid (p<0.01), p-coumaric acid (p<0.001) and their total phenolic content (p<0.001). Honey extracts reduced significantly the viability of PC-3 and MCF-7 cells as well as the expression of adhesion molecules in HAEC. Importantly, vanillic acid content correlated significantly with anticancer activity in PC-3 and MCF-7 cells (p<0.01, p<0.05 respectively). Protocatechuic acid, vanillic acid and total phenolic content correlated significantly with the inhibition of VCAM-1 expression (p<0.05, p<0.05 and p<0.01 respectively). In conclusion, Greek honeys are rich in phenolic acids, in particular protocatechuic and p-hydroxybenzoic acid and exhibit significant antioxidant, anticancer and antiatherogenic activities which may be attributed, at least in part, to their phenolic acid content. PMID:24752205
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NASA Technical Reports Server (NTRS)
Haug, P.; Schnoes, H. K.; Burlingame, A. L.
1971-01-01
Study of solvent extractable acidic constituents of oil shale from the Colorado Green River Formation. Identification of individual components is based on gas chromatographic and mass spectrometric data obtained for their respective methyl esters. Normal acids, isoprenoidal acids, alpha, omega-dicarboxylic acids, mono-alpha-methyl dicarboxylic acids and methyl ketoacids were identified. In addition, the presence of monocyclic, benzoic, phenylalkanoic and naphthyl-carboxylic acids, as well as cycloaromatic acids, is demonstrated by partial identification.
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Liu, Tingwu; Jiang, Xinwu; Shi, Wuliang; Chen, Juan; Pei, Zhenming; Zheng, Hailei
2011-05-01
Acid rain is a worldwide environmental issue that has seriously destroyed forest ecosystems. As a highly effective and broad-spectrum plant resistance-inducing agent, β-aminobutyric acid could elevate the tolerance of Arabidopsis when subjected to simulated acid rain. Using comparative proteomic strategies, we analyzed 203 significantly varied proteins of which 175 proteins were identified responding to β-aminobutyric acid in the absence and presence of simulated acid rain. They could be divided into ten groups according to their biological functions. Among them, the majority was cell rescue, development and defense-related proteins, followed by transcription, protein synthesis, folding, modification and destination-associated proteins. Our conclusion is β-aminobutyric acid can lead to a large-scale primary metabolism change and simultaneously activate antioxidant system and salicylic acid, jasmonic acid, abscisic acid signaling pathways. In addition, β-aminobutyric acid can reinforce physical barriers to defend simulated acid rain stress. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Yang, Yang; Ferro, Miguel Duarte; Cavaco, Isabel; Liang, Yizeng
2013-04-17
In this study, an analytical method for the detection and identification of extra virgin olive oil adulteration with four types of oils (corn, peanut, rapeseed, and sunflower oils) was proposed. The variables under evaluation included 22 fatty acids and 6 other significant parameters (the ratio of linoleic/linolenic acid, oleic/linoleic acid, total saturated fatty acids (SFAs), polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), MUFAs/PUFAs). Univariate analyses followed by multivariate analyses were applied to the adulteration investigation. As a result, the univariate analyses demonstrated that higher contents of eicosanoic acid, docosanoic acid, tetracosanoic acid, and SFAs were the peculiarities of peanut adulteration and higher levels of linolenic acid, 11-eicosenoic acid, erucic acid, and nervonic acid the characteristics of rapeseed adulteration. Then, PLS-LDA made the detection of adulteration effective with a 1% detection limit and 90% prediction ability; a Monte Carlo tree identified the type of adulteration with 85% prediction ability.
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The effect of propionic acid and valeric acid on the cell cycle in root meristems of Pisum sativum
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tramontano, W.A.; Yang, Shauyu; Delillo, A.R.
1990-01-01
Propionic acid and valeric acid at 1mM reduced the mitotic index of root meristem cells of Pisum sativum to < 1% after 12 hr in aerated White's medium. This effect varied with different acid concentrations. After a 12 hr exposure to either acid, seedlings transferred to fresh medium without either acid, resumed their normal mitotic index after 12 hr, with a burst of mitosis 8 hr post-transfer. Exposure of root meristem cells to either acid also inhibited ({sup 3}H)-TdR incorporation. Neither acid significantly altered the distribution of meristematic cells in G1 and G2 after 12 hr. The incorporation of ({supmore » 3}H) - uridine was also unaltered by the addition of either acid. This information suggests that propionic acid and valeric acid, limit progression through the cell cycle by inhibiting DNA synthesis and arresting cells in G1 and G2. These results were consistent with previous data which utilized butyric acid.« less
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Grant-Preece, Paris; Barril, Celia; Schmidtke, Leigh M; Clark, Andrew C
2018-03-15
Model wine solutions containing organic acids, individually or combined, and iron(III), were exposed to light from fluorescent lamps or stored in darkness for four hours. (-)-Epicatechin was then added, and the solutions incubated in darkness for 10days. Browning was monitored by UV-visible absorption spectrophotometry and UHPLC-DAD. The pre-irradiated solutions containing tartaric acid exhibited increased yellow/brown coloration compared to the dark controls mainly due to reaction of the tartaric acid photodegradation product glyoxylic acid with (-)-epicatechin to form xanthylium cation pigments. In these solutions, browning decreased as the concentrations of organic acids other than tartaric acid increased. Xanthylium cations were also detected in the pre-irradiated malic acid solution. However, in the malic acid, succinic acid, citric acid and lactic acid solutions, any coloration was mainly due to the production of dehydrodiepicatechin A, which was largely independent of prior light exposure, but strongly affected by the organic acid present. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Microbial degradation of poly(amino acid)s.
Obst, Martin; Steinbüchel, Alexander
2004-01-01
Natural poly(amino acid)s are a group of poly(ionic) molecules (ionomers) with various biological functions and putative technical applications and play, therefore, an important role both in nature and in human life. Because of their biocompatibility and their synthesis from renewable resources, poly(amino acid)s may be employed for many different purposes covering a broad spectrum of medical, pharmaceutical, and personal care applications as well as the domains of agriculture and of environmental applications. Biodegradability is one important advantage of naturally occurring poly(amino acid)s over many synthetic polymers. The intention of this review is to give an overview about the enzyme systems catalyzing the initial steps in poly(amino acid) degradation. The focus is on the naturally occurring poly(amino acid)s cyanophycin, poly(epsilon-L-lysine) and poly(gamma-glutamic acid); but biodegradation of structurally related synthetic polyamides such as poly(aspartic acid) and nylons, which are known from various technical applications, is also included.
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Beld, Joris; Abbriano, Raffaela; Finzel, Kara; Hildebrand, Mark; Burkart, Michael D
2016-04-01
In both eukaryotes and prokaryotes, fatty acid synthases are responsible for the biosynthesis of fatty acids in an iterative process, extending the fatty acid by two carbon units every cycle. Thus, odd numbered fatty acids are rarely found in nature. We tested whether representatives of diverse microbial phyla have the ability to incorporate odd-chain fatty acids as substrates for their fatty acid synthases and their downstream enzymes. We fed various odd and short chain fatty acids to the bacterium Escherichia coli, cyanobacterium Synechocystis sp. PCC 6803, green microalga Chlamydomonas reinhardtii and diatom Thalassiosira pseudonana. Major differences were observed, specifically in the ability among species to incorporate and elongate short chain fatty acids. We demonstrate that E. coli, C. reinhardtii, and T. pseudonana can produce longer fatty acid products from short chain precursors (C3 and C5), while Synechocystis sp. PCC 6803 lacks this ability. However, Synechocystis can incorporate and elongate longer chain fatty acids due to acyl-acyl carrier protein synthetase (AasS) activity, and knockout of this protein eliminates the ability to incorporate these fatty acids. In addition, expression of a characterized AasS from Vibrio harveyii confers a similar capability to E. coli. The ability to desaturate exogenously added fatty acids was only observed in Synechocystis and C. reinhardtii. We further probed fatty acid metabolism of these organisms by feeding desaturase inhibitors to test the specificity of long-chain fatty acid desaturases. In particular, supplementation with thia fatty acids can alter fatty acid profiles based on the location of the sulfur in the chain. We show that coupling sensitive gas chromatography mass spectrometry to supplementation of unnatural fatty acids can reveal major differences between fatty acid metabolism in various organisms. Often unnatural fatty acids have antibacterial or even therapeutic properties. Feeding of short precursors now gives us easy access to these extended molecules.
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Yang, Lei; Christakou, Eleni; Vang, Jesper; Lübeck, Mette; Lübeck, Peter Stephensen
2017-03-14
C 4 -dicarboxylic acids, including malic acid, fumaric acid and succinic acid, are valuable organic acids that can be produced and secreted by a number of microorganisms. Previous studies on organic acid production by Aspergillus carbonarius, which is capable of producing high amounts of citric acid from varieties carbon sources, have revealed its potential as a fungal cell factory. Earlier attempts to reroute citric acid production into C 4 -dicarboxylic acids have been with limited success. In this study, a glucose oxidase deficient strain of A. carbonarius was used as the parental strain to overexpress a native C 4 -dicarboxylate transporter and the gene frd encoding fumarate reductase from Trypanosoma brucei individually and in combination. Impacts of the introduced genetic modifications on organic acid production were investigated in a defined medium and in a hydrolysate of wheat straw containing high concentrations of glucose and xylose. In the defined medium, overexpression of the C 4 -dicarboxylate transporter alone and in combination with the frd gene significantly increased the production of C 4 -dicarboxylic acids and reduced the accumulation of citric acid, whereas expression of the frd gene alone did not result in any significant change of organic acid production profile. In the wheat straw hydrolysate after 9 days of cultivation, similar results were obtained as in the defined medium. High amounts of malic acid and succinic acid were produced by the same strains. This study demonstrates that the key to change the citric acid production into production of C 4 -dicarboxylic acids in A. carbonarius is the C 4 -dicarboxylate transporter. Furthermore it shows that the C 4 -dicarboxylic acid production by A. carbonarius can be further increased via metabolic engineering and also shows the potential of A. carbonarius to utilize lignocellulosic biomass as substrates for C 4 -dicarboxylic acid production.
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Hamano, Y
2016-08-01
The present study was conducted to determine the effects of α-lipoic acid supplementation on post-mortem changes in the fatty acid profile and concentrations of nucleotide-related substances, especially those of a taste-active compound, inosine 5'-monophosphate, in chicken meat. Mixed-sex broiler chicks aged 14 d were divided into three groups of 16 birds each and were fed on diets supplemented with α-lipoic acid at levels of 0, 100 or 200 mg/kg for 4 weeks. Blood and breast muscle samples were taken at 42 d of age under the fed condition and then after fasting for 18 h. The breast muscle obtained from fasted chickens was subsequently refrigerated at 2°C for one and 3 d. α-Lipoic acid supplementation did not affect any plasma metabolite concentration independently of feeding condition, while a slight increase in plasma glucose concentration was shown with both administration levels of α-lipoic acid. In early post-mortem breast muscle under the fed condition, α-lipoic acid had no effect on concentrations of fatty acids or nucleotides of ATP, ADP, and AMP. In post-mortem breast tissues obtained from fasted chickens, total fatty acid concentrations were markedly increased by α-lipoic acid feeding at 200 mg/kg irrespective of length of refrigeration. This effect was dependent on stearic acid, oleic acid, linoleic acid and linolenic acid. However, among fatty acids, the only predominantly increased unsaturated fatty acid was oleic acid. Dietary supplementation with α-lipoic acid at 200 mg/kg increased the inosine 5'-monophosphate concentration in breast meat and, in contrast, reduced the subsequent catabolites, inosine and xanthine, regardless of the length of refrigeration. Therefore, the present study suggests that α-lipoic acid administration altered the fatty acid profile and improved meat quality by increasing taste-active substances in the post-mortem meat obtained from fasted chickens.
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Organic acids in cloud water and rainwater at a mountain site in acid rain areas of South China.
Sun, Xiao; Wang, Yan; Li, Haiyan; Yang, Xueqiao; Sun, Lei; Wang, Xinfeng; Wang, Tao; Wang, Wenxing
2016-05-01
To investigate the chemical characteristics of organic acids and to identify their source, cloud water and rainwater samples were collected at Mount Lu, a mountain site located in the acid rain-affected area of south China, from August to September of 2011 and March to May of 2012. The volume-weighted mean (VWM) concentration of organic acids in cloud water was 38.42 μeq/L, ranging from 7.45 to 111.46 μeq/L, contributing to 2.50 % of acidity. In rainwater samples, organic acid concentrations varied from 12.39 to 68.97 μeq/L (VWM of 33.39 μeq/L). Organic acids contributed significant acidity to rainwater, with a value of 17.66 %. Formic acid, acetic acid, and oxalic acid were the most common organic acids in both cloud water and rainwater. Organic acids had an obviously higher concentration in summer than in spring in cloud water, whereas there was much less discrimination in rainwater between the two seasons. The contribution of organic acids to acidity was lower during summer than during spring in both cloud water (2.20 % in summer vs 2.83 % in spring) and rainwater (12.24 % in summer vs 19.89 % in spring). The formic-to-acetic acid ratio (F/A) showed that organic acids were dominated by primary emissions in 71.31 % of the cloud water samples and whole rainwater samples. Positive matrix factorization (PMF) analysis determined four factors as the sources of organic acids in cloud water, including biogenic emissions (61.8 %), anthropogenic emissions (15.28 %), marine emissions (15.07 %) and soil emissions (7.85 %). The findings from this study imply an indispensable role of organic acids in wet deposition, but organic acids may have a limited capacity to increase ecological risks in local environments.
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Increase in the permeability of tonoplast of garlic (Allium sativum) by monocarboxylic acids.
Bai, Bing; Li, Lei; Hu, Xiaosong; Wang, Zhengfu; Zhao, Guanghua
2006-10-18
Immersion of intact aged garlic (Allium sativum) cloves in a series of 5% weak organic monocarboxylate solutions (pH 2.0) resulted in green color formation. No color was formed upon treatment with other weak organic acids, such as citric and malic acids, and the inorganic hydrochloric acid under the same conditions. To understand the significance of monocarboxylic acids and their differing function from that of other acids, acetic acid was compared with organic acids citric and malic and the inorganic hydrochloric acid. The effects of these acids on the permeability of plasma and intracellular membrane of garlic cells were measured by conductivity, light microscopy, and transmission electron microscopy. Except for hydrochloric acid, treatment of garlic with all three organic acids greatly increased the relative conductivity of their respective pickling solutions, indicating that all tested organic acids increased the permeability of plasma membrane. Moreover, a pickling solution containing acetic acid exhibited 1.5-fold higher relative conductivity (approximately 90%) as compared to those (approximately 60%) of both citric and malic acids, implying that exposure of garlic cloves to acetic acid not only changed the permeability of the plasma membrane but also increased the permeability of intracellular membrane. Exposure of garlic to acetic acid led to the production of precipitate along the tonoplast, but no precipitate was formed by citric and malic acids. This indicates that the structure of the tonoplast was damaged by this treatment. Further support for this conclusion comes from results showing that the concentration of thiosulfinates [which are produced only by catalytic conversion of S-alk(en)yl-l-cysteine sulfoxides in cytosol by alliinase located in the vacuole] in the acetic acid pickling solution is 1.3 mg/mL, but almost no thiosulfinates were detected in the pickling solution of citric and malic acids. Thus, all present results suggest that damage of tonoplast by treatment with monocarboxylates such as acetic acid may be the main reason for the greening of garlic.
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21 CFR 172.852 - Glyceryl-lacto esters of fatty acids.
Code of Federal Regulations, 2014 CFR
2014-04-01
... § 172.852 Glyceryl-lacto esters of fatty acids. Glyceryl-lacto esters of fatty acids (the lactic acid... conditions: (a) They are manufactured from glycerin, lactic acid, and fatty acids conforming with § 172.860...
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New insights into bile acid malabsorption.
Johnston, Ian; Nolan, Jonathan; Pattni, Sanjeev S; Walters, Julian R F
2011-10-01
Bile acid malabsorption occurs when there is impaired absorption of bile acids in the terminal ileum, so interrupting the normal enterohepatic circulation. The excess bile acids in the colon cause diarrhea, and treatment with bile acid sequestrants is beneficial. The condition can be diagnosed with difficulty by measuring fecal bile acids, or more easily by retention of selenohomocholyltaurine (SeHCAT), where this is available. Chronic diarrhea caused by primary bile acid diarrhea appears to be common, but is under-recognized where SeHCAT testing is not performed. Measuring excessive bile acid synthesis with 7α-hydroxy-4-cholesten-3-one may be an alternative means of diagnosis. It appears that there is no absorption defect in primary bile acid diarrhea but, instead, an overproduction of bile acids. Fibroblast growth factor 19 (FGF19) inhibits hepatic bile acid synthesis. Defective production of FGF19 from the ileum may be the cause of primary bile acid diarrhea.
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Discovery of essential fatty acids
Spector, Arthur A.; Kim, Hee-Yong
2015-01-01
Dietary fat was recognized as a good source of energy and fat-soluble vitamins by the first part of the 20th century, but fatty acids were not considered to be essential nutrients because they could be synthesized from dietary carbohydrate. This well-established view was challenged in 1929 by George and Mildred Burr who reported that dietary fatty acid was required to prevent a deficiency disease that occurred in rats fed a fat-free diet. They concluded that fatty acids were essential nutrients and showed that linoleic acid prevented the disease and is an essential fatty acid. The Burrs surmised that other unsaturated fatty acids were essential and subsequently demonstrated that linolenic acid, the omega-3 fatty acid analog of linoleic acid, is also an essential fatty acid. The discovery of essential fatty acids was a paradigm-changing finding, and it is now considered to be one of the landmark discoveries in lipid research. PMID:25339684
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Preparation of a Ammonia-Treated Lac Dye and Structure Elucidation of Its Main Component.
Nishizaki, Yuzo; Ishizuki, Kyoko; Akiyama, Hiroshi; Tada, Atsuko; Sugimoto, Naoki; Sato, Kyoko
2016-01-01
Lac dye and cochineal extract contain laccaic acids and carminic acid as the main pigments, respectively. Both laccaic acids and carminic acid are anthraquinone derivatives. 4-Aminocarminic acid (acid-stable carmine), an illegal colorant, has been detected in several processed foods. 4-Aminocarminic acid is obtained by heating cochineal extract (carminic acid) in ammonia solution. We attempted to prepare ammonia-treated lac dye and to identify the structures of the main pigment components. Ammonia-treated lac dye showed acid stability similar to that of 4-aminocarminic acid. The structures of the main pigments in ammonia-treated lac dye were analyzed using LC/MS. One of the main pigments was isolated and identified as 4-aminolaccaic acid C using various NMR techniques, including 2D-INADEQUATE. These results indicated that ammonia-treatment of lac dye results in the generation of 4-aminolaccaic acids.
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Enhancement of hydrolysis of Chlorella vulgaris by hydrochloric acid.
Park, Charnho; Lee, Ja Hyun; Yang, Xiaoguang; Yoo, Hah Young; Lee, Ju Hun; Lee, Soo Kweon; Kim, Seung Wook
2016-06-01
Chlorella vulgaris is considered as one of the potential sources of biomass for bio-based products because it consists of large amounts of carbohydrates. In this study, hydrothermal acid hydrolysis with five different acids (hydrochloric acid, nitric acid, peracetic acid, phosphoric acid, and sulfuric acid) was carried out to produce fermentable sugars (glucose, galactose). The hydrothermal acid hydrolysis by hydrochloric acid showed the highest sugar production. C. vulgaris was hydrolyzed with various concentrations of hydrochloric acid [0.5-10 % (w/w)] and microalgal biomass [20-140 g/L (w/v)] at 121 °C for 20 min. Among the concentrations examined, 2 % hydrochloric acid with 100 g/L biomass yielded the highest conversion of carbohydrates (92.5 %) into reducing sugars. The hydrolysate thus produced from C. vulgaris was fermented using the yeast Brettanomyces custersii H1-603 and obtained bioethanol yield of 0.37 g/g of algal sugars.
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Cox-2 inhibitory effects of naturally occurring and modified fatty acids.
Ringbom, T; Huss, U; Stenholm , A; Flock, S; Skattebøl, L; Perera, P; Bohlin, L
2001-06-01
In the search for new cyclooxygenase-2 (COX-2) selective inhibitors, the inhibitory effects of naturally occurring fatty acids and some of their structural derivatives on COX-2-catalyzed prostaglandin biosynthesis were investigated. Among these fatty acids, linoleic acid (LA), alpha-linolenic acid (alpha-LNA), myristic acid, and palmitic acid were isolated from a CH(2)Cl(2) extract of the plant Plantago major by bioassay-guided fractionation. Inhibitory effects of other natural, structurally related fatty acids were also investigated: stearic acid, oleic acid, pentadecanoic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Further, the inhibitory effects of these compounds on COX-2- and COX-1-catalyzed prostaglandin biosynthesis was compared with the inhibition of some synthesized analogues of EPA and DHA with ether or thioether functions. The most potent COX-2-catalyzed prostaglandin biosynthesis inhibitor was all-(Z)-5-thia-8,11,14,17-eicosatetraenoic acid (2), followed by EPA, DHA, alpha-LNA, LA, (7E,11Z,14Z,17Z)-5-thiaeicosa-7,11,14,17-tetraenoic acid, all-(Z)-3-thia-6,9,12,15-octadecatetraenoic acid, and (5E,9Z,12Z,15Z,18Z)-3-oxaheneicosa-5,9,12,15,18-pentaenoic acid, with IC(50) values ranging from 3.9 to180 microM. The modified compound 2 and alpha-LNA were most selective toward COX-2, with COX-2/COX-1 ratios of 0.2 and 0.1, respectively. This study shows that several of the natural fatty acids as well as all of the semisynthetic thioether-containing fatty acids inhibited COX-2-catalyzed prostaglandin biosynthesis, where alpha-LNA and compound 2 showed selectivity toward COX-2.
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Tall oil precursors and turpentine in Jack and Eastern White Pine
DOE Office of Scientific and Technical Information (OSTI.GOV)
Conner, A.H.; Diehl, M.A.; Rowe, J.W.
1980-04-01
The tall oil precursors and turpentine from jack pine (Pinus banksiana Lamb.) and eastern white pine (Pinus strobus L.) were investigated. The tall oil precursors (resin acids, fatty acids, and unsaponifiables were determined by chemical fractionation of the nonvolatile diethyl ether extractives (NVEE) of these speices: (approximate % resin acids, % fatty acids, % unsaponifiables, and % acids other that fatty and resin acids) - jack pine sapwood (10, 60, 10, 20%), heartwood (38, 12, 6, 44%); eastern white pine sapwood (11, 57, 9, 22%), and heartwood (11, 18, 10, 62%). The resin acids were a mixture of the pimaricmore » and abietic acids common to pines. In addition, eastern white pine contained major amounts of the resin acid, anticopalic acid. The fatty acids were predominately oleic, linoleic, and 5, 9, 12-octadecatrienoic acids. The unsaponsiables were a complex mixture of diterpenes and sterols (mainly campesterol and sitosterol). On treating these species with paraquat, lightwood occurred in the sapwood but not in the heartwood areas as we have oberved with other pines. The NVEE of the lightwood areas contained increased amounts of resin acids, unsaponifiables, and acids other than fatty and resin acids. The total fatty acid content was essentially unchanged. Since fatty acid components are preferentially lost by esterification with neutral alcoholic constituents in the unsaponifiables during the distillation refining of crude tall oil, the increased unsaponifiables relative to the constant fatty acid content might result in a net reduction in fatty acid recovery from lightered trees. The turpentine content of both jack and eastern white pine increased on lightering and was primarily a mixture of ..cap alpha..- and ..beta..-pinene.« less
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Catalytic conversion of lactic acid and its derivatives
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kokitkar, P.B.; Langford, R.; Miller, D.J.
1993-12-31
The catalytic upgrading of lactic acid and methyl lactate is being investigated. With the commercialization of inexpensive starch fermentation technologies, US production of lactic acid is undergoing a surge. Dropping cost and increased availability offer a major opportunity to develop lactic acid as a renewable feedstock for chemicals production. IT can be catalytically converted into several important chemical intermediates currently derived from petroleum including acrylic acid, propanoic acid, and 2,3-pentanedione. The process can expand the potential of biomass as a substitute feedstock for petroleum and can benefit both the US chemical process industry and US agriculture via increased production ofmore » high-value, non-food products from crops and crop byproducts. Reaction studies of lactic acid and its ester are conducted in fixed bed reactors at 250-380{degrees}C and 0.1-0.5 MPa (1-5 atm) using salt catalysts on low surface area supports. Highest selectivities achieved are 42% to acrylic acid and 55% to 2,3-pentanedione from lactic acid over NaNO{sub 3} catalyst on low surface area silica support. High surface area (microporous) or highly acidic supports promote fragmentation to acetaldehyde and thus reduce yields of desirable products. The support acidity gives rice to lactic acid from neat methyl lactate feed but the lactic acid yield goes down after the nitrate salt is impregnated on the support. Both lactic acid and methyl lactate form 2,3-pentanedione. Methyl lactate reactions are more complex since it forms all the products obtained from lactic acid as well as many corresponding esters of the acids obtained from lactic acid (mainly methyl acrylate, methyl propionate, methyl acetate). At high temperatures, methyl acetate and acetic acid yields become significant from methyl lactate whereas lactic acid gives significant amount of acetol at high temperatures.« less
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Kefir Grains Change Fatty Acid Profile of Milk during Fermentation and Storage
Vieira, C. P.; Álvares, T. S.; Gomes, L. S.; Torres, A. G.; Paschoalin, V. M. F.; Conte-Junior, C. A.
2015-01-01
Several studies have reported that lactic acid bacteria may increase the production of free fatty acids by lipolysis of milk fat, though no studies have been found in the literature showing the effect of kefir grains on the composition of fatty acids in milk. In this study the influence of kefir grains from different origins [Rio de Janeiro (AR), Viçosa (AV) e Lavras (AD)], different time of storage, and different fat content on the fatty acid content of cow milk after fermentation was investigated. Fatty acid composition was determined by gas chromatography. Values were considered significantly different when p<0.05. The highest palmitic acid content, which is antimutagenic compost, was seen in AV grain (36.6g/100g fatty acids), which may have contributed to increasing the antimutagenic potential in fermented milk. Higher monounsaturated fatty acid (25.8g/100g fatty acids) and lower saturated fatty acid (72.7g/100g fatty acids) contents were observed in AV, when compared to other grains, due to higher Δ9-desaturase activity (0.31) that improves the nutritional quality of lipids. Higher oleic acid (25.0g/100g fatty acids) and monounsaturated fatty acid (28.2g/100g fatty acids) and lower saturated fatty acid (67.2g/100g fatty acids) contents were found in stored kefir relatively to fermented kefir leading to possible increase of antimutagenic and anticarcinogenic potential and improvement of nutritional quality of lipids in storage milk. Only high-lipidic matrix displayed increase polyunsaturated fatty acids after fermentation. These findings open up new areas of study related to optimizing desaturase activity during fermentation in order to obtaining a fermented product with higher nutritional lipid quality. PMID:26444286
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Reduction of volatile acidity of acidic wines by immobilized Saccharomyces cerevisiae cells.
Vilela, A; Schuller, D; Mendes-Faia, A; Côrte-Real, M
2013-06-01
Excessive volatile acidity in wines is a major problem and is still prevalent because available solutions are nevertheless unsatisfactory, namely, blending the filter-sterilized acidic wine with other wines of lower volatile acidity or using reverse osmosis. We have previously explored the use of an empirical biological deacidification procedure to lower the acetic acid content of wines. This winemaker's enological practice, which consists in refermentation associated with acetic acid consumption by yeasts, is performed by mixing the acidic wine with freshly crushed grapes, musts, or marc from a finished wine fermentation. We have shown that the commercial strain Saccharomyces cerevisiae S26 is able to decrease the volatile acidity of acidic wines with a volatile acidity higher than 1.44 g L(-1) acetic acid, with no detrimental impact on wine aroma. In this study, we aimed to optimize the immobilization of S26 cells in alginate beads for the bioreduction of volatile acidity of acidic wines. We found that S26 cells immobilized in double-layer alginate-chitosan beads could reduce the volatile acidity of an acidic wine (1.1 g L(-1) acetic acid, 12.5 % (v/v) ethanol, pH 3.12) by 28 and 62 % within 72 and 168 h, respectively, associated with a slight decrease in ethanol concentration (0.7 %). Similar volatile acidity removal efficiencies were obtained in medium with high glucose concentration (20 % w/v), indicating that this process may also be useful in the deacidification of grape musts. We, therefore, show that immobilized S. cerevisiae S26 cells in double-layer beads are an efficient alternative to improve the quality of wines with excessive volatile acidity.
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Yogeeta, Surinder Kumar; Hanumantra, Rao Balaji Raghavendran; Gnanapragasam, Arunachalam; Senthilkumar, Subramanian; Subhashini, Rajakannu; Devaki, Thiruvengadam
2006-05-01
The present study aims at evaluating the effect of the combination of ferulic acid and ascorbic acid on isoproterenol-induced abnormalities in lipid metabolism. The rats were divided into eight groups: Control, isoproterenol, ferulic acid alone, ascorbic acid alone, ferulic acid+ascorbic acid, ferulic acid+isoproterenol, ascorbic acid+isoproterenol and ferulic acid+ascorbic acid+isoproterenol. Ferulic acid (20 mg/kg b.w.t.) and ascorbic acid (80 mg/kg b.w.t.) both alone and in combination was administered orally for 6 days and on the fifth and the sixth day, isoproterenol (150 mg/kg b.w.t.) was injected intraperitoneally to induce myocardial injury to rats. Induction of rats with isoproterenol resulted in a significant increase in the levels of triglycerides, total cholesterol, free fatty acids, free and ester cholesterol in both serum and cardiac tissue. A rise in the levels of phospholipids, lipid peroxides, low density lipoprotein and very low density lipoprotein-cholesterol was also observed in the serum of isoproterenol-intoxicated rats. Further, a decrease in the level of high density lipoprotein in serum and in the phospholipid levels, in the heart of isoproterenol-intoxicated rats was observed, which was paralleled by abnormal activities of lipid metabolizing enzymes: total lipase, cholesterol ester synthase, lipoprotein lipase and lecithin: cholesterol acyl transferase. Pre-cotreatment with the combination of ferulic acid and ascorbic acid significantly attenuated these alterations and restored the levels to near normal when compared to individual treatment groups. Histopathological observations were also in correlation with the biochemical parameters. These findings indicate the synergistic protective effect of ferulic acid and ascorbic acid on isoproterenol-induced abnormalities in lipid metabolism.
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Kefir Grains Change Fatty Acid Profile of Milk during Fermentation and Storage.
Vieira, C P; Álvares, T S; Gomes, L S; Torres, A G; Paschoalin, V M F; Conte-Junior, C A
2015-01-01
Several studies have reported that lactic acid bacteria may increase the production of free fatty acids by lipolysis of milk fat, though no studies have been found in the literature showing the effect of kefir grains on the composition of fatty acids in milk. In this study the influence of kefir grains from different origins [Rio de Janeiro (AR), Viçosa (AV) e Lavras (AD)], different time of storage, and different fat content on the fatty acid content of cow milk after fermentation was investigated. Fatty acid composition was determined by gas chromatography. Values were considered significantly different when p<0.05. The highest palmitic acid content, which is antimutagenic compost, was seen in AV grain (36.6g/100g fatty acids), which may have contributed to increasing the antimutagenic potential in fermented milk. Higher monounsaturated fatty acid (25.8 g/100g fatty acids) and lower saturated fatty acid (72.7 g/100g fatty acids) contents were observed in AV, when compared to other grains, due to higher Δ9-desaturase activity (0.31) that improves the nutritional quality of lipids. Higher oleic acid (25.0 g/100g fatty acids) and monounsaturated fatty acid (28.2g/100g fatty acids) and lower saturated fatty acid (67.2g/100g fatty acids) contents were found in stored kefir relatively to fermented kefir leading to possible increase of antimutagenic and anticarcinogenic potential and improvement of nutritional quality of lipids in storage milk. Only high-lipidic matrix displayed increase polyunsaturated fatty acids after fermentation. These findings open up new areas of study related to optimizing desaturase activity during fermentation in order to obtaining a fermented product with higher nutritional lipid quality.
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Woo, Ji-Min; Kim, Ji-Won; Song, Ji-Won; Blank, Lars M; Park, Jin-Byung
The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid)-induced stress. The metabolic and genomic responses of E. coli BL21(DE3) and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR) system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3). Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3) expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1)) into n-heptanoic acid (5) and 11-hydroxyundec-9-enoic acid (4). This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass.
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Han, Stanisław; Karłowicz-Bodalska, Katarzyna; Potaczek, Piotr; Wójcik, Adam; Ozimek, Lukasz; Szura, Dorota; Musiał, Witold
2014-02-01
The identification of new contaminants is critical in the development of new medicinal products. Many impurities, such as pentanedioic acid, hexanedioic acid, heptanedioic acid, octanedioic acid, decanedioic acid, undecanedioic acid, dodecanedioic acid, tridecanedioic acid, and tetradecanedioic acid, have been identified in samples of azelaic acid. The aim of this study was to identify impurities observed during the stability tests of a new liposomal dosage form of azelaic acid that is composed of phosphatidylcholine and a mixture of ethyl alcohol and water, using high-performance liquid chromatography with evaporative light-scattering detector (HPLC-ELSD), gas chromatography-flame ionisation detection (GC-FID), and gas chromatography-mass spectrometry (GC-MS) methods. During the research and development of a new liposomal formulation of azelaic acid, we developed a method for determining the contamination of azelaic acid using HPLC-ELSD. During our analytical tests, we identified a previously unknown impurity of a liposomal preparation of azelaic acid that appeared in the liposomal formulation of azelaic acid during preliminary stability studies. The procedure led to the conclusion that the impurity was caused by the reaction of azelaic acid with one of the excipients that was applied in the product. The impurity was finally identified as an ethyl monoester of azelaic acid. The identification procedure of this compound was carried out in a series of experiments comparing the chromatograms that were obtained via the following chromatographic methods: HPLC-ELSD, GC-FID, and GC-MS. The final identification of the compound was carried out by GC with MS.
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Wang, Ying; Wu, Feng-Zhi; Wang, Yu-Yan
2011-11-01
Taking cucumber cultivars' Jinlv No. 5' (salt-tolerant) and 'Jinyou No. 1' (salt-sensitive) as test materials, a pot experiment was conducted to study the effects of applying cinnamic acid on the accumulation of applied cinnamic acid in cucumber seedling-soil system under NaCl (585 mg x kg(-1) soil) stress. The concentration of applied cinnamic acid was the main factor affecting the accumulation of the exogenous cinnamic acid in the cucumber plant and soil. With the increasing concentration of applied cinnamic acid, except in the treatment of highest concentration (200 mg x kg(-1) soil) cinnamic acid, the total content of cinnamic acid in cucumber plant was increased. NaCl stress enhanced the toxicity of cinnamic acid. In the treatments of low and medium concentration cinnamic acid, the cinnamic acid content in cucumber plant increased; whereas in the treatments of high concentration cinnamic acid, the decline of the seedlings growth was observed, and led to the decrease of the cinnamic acid content in the plant. The content of cinnamic acid in 'Jinlv No. 5' plant decreased at the concentration of applied cinnamic acid being > 200 mg x kg(-1) soil, while that in 'Jinyou No. 1' started to decrease when the concentration of applied cinnamic acid was > 100 mg x kg(-1) soil, reflecting the discrepancy in salt tolerance of the two cultivars. For the cucumber plant, its leaf had the highest content of cinnamic acid. In the cucumber seedling-soil system, most of applied cinnamic acid was mainly accumulated in soil.
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Uric acid ameliorates indomethacin-induced enteropathy in mice through its antioxidant activity.
Yasutake, Yuichi; Tomita, Kengo; Higashiyama, Masaaki; Furuhashi, Hirotaka; Shirakabe, Kazuhiko; Takajo, Takeshi; Maruta, Koji; Sato, Hirokazu; Narimatsu, Kazuyuki; Yoshikawa, Kenichi; Okada, Yoshikiyo; Kurihara, Chie; Watanabe, Chikako; Komoto, Shunsuke; Nagao, Shigeaki; Matsuo, Hirotaka; Miura, Soichiro; Hokari, Ryota
2017-11-01
Uric acid is excreted from blood into the intestinal lumen, yet the roles of uric acid in intestinal diseases remain to be elucidated. The study aimed to determine whether uric acid could reduce end points associated with nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy. A mouse model of NSAID-induced enteropathy was generated by administering indomethacin intraperitoneally to 8-week-old male C57BL/6 mice, and then vehicle or uric acid was administered orally. A group of mice treated with indomethacin was also concurrently administered inosinic acid, a uric acid precursor, and potassium oxonate, an inhibitor of uric acid metabolism, intraperitoneally. For in vitro analysis, Caco-2 cells treated with indomethacin were incubated in the presence or absence of uric acid. Oral administration of uric acid ameliorated NSAID-induced enteropathy in mice even though serum uric acid levels did not increase. Intraperitoneal administration of inosinic acid and potassium oxonate significantly elevated serum uric acid levels and ameliorated NSAID-induced enteropathy in mice. Both oral uric acid treatment and intraperitoneal treatment with inosinic acid and potassium oxonate significantly decreased lipid peroxidation in the ileum of mice with NSAID-induced enteropathy. Treatment with uric acid protected Caco-2 cells from indomethacin-induced oxidative stress, lipid peroxidation, and cytotoxicity. Uric acid within the intestinal lumen and in serum had a protective effect against NSAID-induced enteropathy in mice, through its antioxidant activity. Uric acid could be a promising therapeutic target for NSAID-induced enteropathy. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
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Method for production of petroselinic acid and OMEGA12 hexadecanoic acid in transgenic plants
Ohlrogge, John B.; Cahoon, Edgar B.; Shanklin, John; Somerville, Christopher R.
1995-01-01
The present invention relates to a process for producing lipids containing the fatty acid petroselinic acid in plants. The production of petroselinic acid is accomplished by genetically transforming plants which do not normally accumulate petroselinic acid with a gene for a .omega.12 desaturase from another species which does normally accumulate petroselinic acid.
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21 CFR 172.848 - Lactylic esters of fatty acids.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Lactylic esters of fatty acids. 172.848 Section 172... CONSUMPTION Multipurpose Additives § 172.848 Lactylic esters of fatty acids. Lactylic esters of fatty acids... prepared from lactic acid and fatty acids meeting the requirements of § 172.860(b) and/or oleic acid...
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Chemical Characterization and Toxicologic Evaluation of Airborne Mixtures
1981-04-01
in the chamber air (",50% relative humidity) that phosphoric acid would be the principal component of the...triphosphoric, and tetrametaphosphoric acids were present; trimeta- phosphoric and tetrapolyphosporic acids may also have been present in trace amounts. The...triphosphoric acid , diphosphoric acid , and phosphoric acid are all strong acids that, with strong bases, can be titrated in water. Titration
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ERIC Educational Resources Information Center
Damonte, Kathleen
2004-01-01
The term acid rain describes rain, snow, or fog that is more acidic than normal precipitation. To understand what acid rain is, it is first necessary to know what an acid is. Acids can be defined as substances that produce hydrogen ions (H+), when dissolved in water. Scientists indicate how acidic a substance is by a set of numbers called the pH…
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21 CFR 172.350 - Fumaric acid and salts of fumaric acid.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Fumaric acid and salts of fumaric acid. 172.350... HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172.350 Fumaric acid and salts of fumaric acid. Fumaric acid and its calcium, ferrous, magnesium, potassium, and sodium salts may be safely used...
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Luo, Yu; Huang, Yi; Yuan, Xiaohong; Zhang, Lei; Zhang, Xinyi; Gao, Ping
2017-01-01
To better understand the medicinal and nutritional value of mushrooms, we studied the fatty acid (FA) compositions and DPPH scavenging abilities of 11 mushrooms from Southwest China. The crude fat (CF) contents were examined initially, then 3 methods of FA methyl esterification were compared to identify which acid treatment was the most appropriate method. Then methyl esterification methods for 12 CFs were performed with acid treatment and the FA compositions were analyzed with gas chromatography-mass spectrometry. The results showed that tetradecanoic acid (14:0), hexadecenoic acid (16:1), hexadecanoic acid (16:0), heptadecanoic acid (17:0), octadecadienoic acid (18:2), octadecenoic acid (18:1), octadecanoic acid (18:0), docosanoic acid (22:0), and tetracosanoic acid (24:0) were detected in all the samples, with large amounts of hexadecanoic acid (16:0), octadecadienoic acid (18:2), octadecenoic acid (18:1), and octadecanoic acid (18:0). Daldinia eschscholtzii and Sarcodon imbricatus had the highest ratio value of unsaturated FAs to saturated FAs (4.33 and 3.03, respectively). The DPPH scavenging ability of 12 CFs was also tested. The free radical scavenging rates of the CFs were almost < 10% at a concentration of 0.10 mg/mL, except that of S. imbricatus, which reached 81.25%, with a half-maximal inhibitory concentration of 0.054 mg/mL. This strong DPPH free radical scavenging ability of S. imbricatus may be related to α-hydroxy FA.
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Enantiomeric Excesses of Acid Labile Amino Acid Precursors of the Murchison Meteorite
NASA Astrophysics Data System (ADS)
Pizzarello, Sandra
1998-10-01
Amino acids present in carbonaceous chondrite are extracted in water in part as free compounds and in approximately equal part as acid labile precursors. On the assumption that they would be free of contamination, the precursors of two Murchison amino acids that have terrestrial occurrence, alanine and glutamic acid, have been targeted for analysis of their enantiomeric ratios. Pyroglutamic acid, the precursor of glutamic acid, was found with an L-enantiomeric excess comparable to that of the free acid, while alanine's precursor, N-acetyl alanine, appears approximately racemic. Also alpha-imino propioacetic acid, a proposed end product of alanine synthesis in the meteorite, was analyzed and found racemic.
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Enantiomeric Excesses of Acid Labile Amino Acid Precursors of the Murchison Meteorite
NASA Technical Reports Server (NTRS)
Pizzarello, Sandra
1998-01-01
Amino acids present in carbonaceous chondrite are extracted in water in part as free compounds and in approximately equal part as acid labile precursors. On the assumption that they would be free of contamination, the precursors of two Murchison amino acids that have terrestrial occurrence, alanine and glutamic acid, have been targeted for analysis of their enantiomeric ratios. Pyroglutamic acid, the precursor of glutamic acid, was found with an L-enantiomeric excess comparable to that of the free acid, while alanine's precursor, N-acetyl alanine, appears approximately racemic. Also alpha-imino propioacetic acid, a proposed end product of alanine synthesis in the meteorite, was analyzed and found racemic.
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NASA Technical Reports Server (NTRS)
Reihs, Christa M.; Golden, David M.; Tolbert, Margaret A.
1990-01-01
The uptake of nitric acid by sulfuric acid solutions representative of stratospheric particulate at low temperatures was measured to determine the solubility of nitric acid in sulfuric acid solutions as a function of H2SO4 concentration and solution temperature. Solubilities are reported for sulfuric acid solutions ranging from 58 to 87 wt pct H2SO4 over a temperature range from 188 to 240 K, showing that, in general, the solubility of nitric acid increases with decreasing sulfuric acid concentration and with decreasing temperature. The measured solubilities indicate that nitric acid in the global stratosphere will be found predominantly in the gas phase.
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Pegolo, S; Stocco, G; Mele, M; Schiavon, S; Bittante, G; Cecchinato, A
2017-04-01
Buffalo milk is the world's second most widely produced milk, and increasing attention is being paid to its composition, particularly the fatty acid profile. The objectives of the present study were (1) to characterize the fatty acid composition of Mediterranean buffalo milk, and (2) to investigate potential sources of variation in the buffalo milk fatty acid profile. We determined the profile of 69 fatty acid traits in 272 individual samples of Mediterranean buffalo milk using gas chromatography. In total, 51 individual fatty acids were identified: 24 saturated fatty acids, 13 monounsaturated fatty acids, and 14 polyunsaturated fatty acids. The major individual fatty acids in buffalo milk were in the order 16:0, 18:1 cis-9, 14:0, and 18:0. Saturated fatty acids were the predominant fraction in buffalo milk fat (70.49%); monounsaturated and polyunsaturated fatty acids were at 25.95 and 3.54%, respectively. Adopting a classification based on carbon-chain length, we found that medium-chain fatty acids (11-16 carbons) represented the greater part (53.7%) of the fatty acid fraction of buffalo milk, whereas long-chain fatty acids (17-24 carbons) and short-chain fatty acids (4-10 carbons) accounted for 32.73 and 9.72%, respectively. The n-3 and n-6 fatty acids were 0.46 and 1.77%, respectively. The main conjugated linoleic acid, rumenic acid, represented 0.45% of total milk fatty acids. Herd/test date and stage of lactation were confirmed as important sources of variation in the fatty acid profile of buffalo milk. The percentages of short-chain and medium-chain fatty acids in buffalo milk increased in early lactation (+0.6 and +3.5%, respectively), whereas long-chain fatty acids decreased (-4.2%). The only exception to this pattern was butyric acid, which linearly decreased from the beginning of lactation, confirmation that its synthesis is independent of malonyl-CoA. These results seem to suggest that in early lactation the mobilization of energy reserves may have less influence on the fatty acid profile of buffalo milk than that of cow milk, probably due to a shorter and less severe period of negative energy balance. Parity affected the profiles of a few traits and had the most significant effects on branched-chain fatty acids. This work provided a detailed overview of the fatty acid profile in buffalo milk including also those fatty acids present in small concentrations, which may have beneficial effects for human health. Our results contributed also to increase the knowledge about the effects of some of the major factors affecting buffalo production traits and fatty acid concentrations in milk, and consequently its technological and nutritional properties. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
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[Effect of Gram-negative bacteria on fatty acids].
Vuillemin, N; Dupeyron, C; Leluan, G; Bory, J
1981-01-01
The gram-negative bacteria investigated exert various effects on fatty acids. P. aeruginosa and A. calcoaceticus catabolize any of the fatty acids tested. S. marcescens is effective upon all fatty acids excepting butyric acid. The long chain fatty acids only are degraded by E. coli, meanwhile the other fatty acids present a bacteriostatic or bactericidal activity on it. The authors propose a simple and original method for testing the capability of degradation of fatty acids by some bacterial species.
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Qi, Baoxiu
2014-01-01
IgASE1, a C18 Δ9-specific polyunsaturated fatty acid elongase from the marine microalga Isochrysis galbana, is able to convert linoleic acid and α-linolenic acid to eicosadienoic acid and eicosatrienoic acid in Arabidopsis. Eicosadienoic acid and eicosatrienoic acid are precursors of arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, which are synthesized via the Δ8 desaturation biosynthetic pathways. This study shows that the IgASE1-expressing transgenic Arabidopsis exhibited altered morphology (decreased leaf area and biomass) and enhanced drought resistance compared to wild-type plants. The transgenic Arabidopsis were hypersensitive to abscisic acid (ABA) during seed germination, post-germination growth, and seedling development. They had elevated leaf ABA levels under well-watered and dehydrated conditions and their stomata were more sensitive to ABA. Exogenous application of eicosadienoic acid and eicosatrienoic acid can mimic ABA and drought responses in the wild type plants, similar to that found in the transgenic ones. The transcript levels of genes involved in the biosynthesis of ABA (NCED3, ABA1, AAO3) as well as other stress-related genes were upregulated in this transgenic line upon osmotic stress (300mM mannitol). Taken together, these results indicate that these two eicosapolyenoic acids or their derived metabolites can mitigate the effects of drought in transgenic Arabidopsis, at least in part, through the action of ABA. PMID:24609499
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Yuan, Xiaowei; Li, Yaxiao; Liu, Shiyang; Xia, Fei; Li, Xinzheng; Qi, Baoxiu
2014-04-01
IgASE1, a C₁₈ Δ(9)-specific polyunsaturated fatty acid elongase from the marine microalga Isochrysis galbana, is able to convert linoleic acid and α-linolenic acid to eicosadienoic acid and eicosatrienoic acid in Arabidopsis. Eicosadienoic acid and eicosatrienoic acid are precursors of arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, which are synthesized via the Δ(8) desaturation biosynthetic pathways. This study shows that the IgASE1-expressing transgenic Arabidopsis exhibited altered morphology (decreased leaf area and biomass) and enhanced drought resistance compared to wild-type plants. The transgenic Arabidopsis were hypersensitive to abscisic acid (ABA) during seed germination, post-germination growth, and seedling development. They had elevated leaf ABA levels under well-watered and dehydrated conditions and their stomata were more sensitive to ABA. Exogenous application of eicosadienoic acid and eicosatrienoic acid can mimic ABA and drought responses in the wild type plants, similar to that found in the transgenic ones. The transcript levels of genes involved in the biosynthesis of ABA (NCED3, ABA1, AAO3) as well as other stress-related genes were upregulated in this transgenic line upon osmotic stress (300 mM mannitol). Taken together, these results indicate that these two eicosapolyenoic acids or their derived metabolites can mitigate the effects of drought in transgenic Arabidopsis, at least in part, through the action of ABA.
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Paudyal, Ranju; Barnes, Ruth H; Karatzas, Kimon Andreas G
2018-02-01
Here it is demonstrated a novel approach in disinfection regimes where specific molecular acid resistance systems are inhibited aiming to eliminate microorganisms under acidic conditions. Despite the importance of the Glutamate Decarboxylase (GAD) system for survival of Listeria monocytogenes and other pathogens under acidic conditions, its potential inhibition by specific compounds that could lead to its elimination from foods or food preparation premises has not been studied. The effects of maleic acid on the acid resistance of L. monocytogenes were investigated and found that it has a higher antimicrobial activity under acidic conditions than other organic acids, while this could not be explained by its pKa or Ka values. The effects were found to be more pronounced on strains with higher GAD activity. Maleic acid affected the extracellular GABA levels while it did not affect the intracellular ones. Maleic acid had a major impact mainly on GadD2 activity as also shown in cell lysates. Furthermore, it was demonstrated that maleic acid is able to partly remove biofilms of L. monocytogenes. Maleic acid is able to inhibit the GAD of L. monocytogenes significantly enhancing its sensitivity to acidic conditions and together with its ability to remove biofilms, make a good candidate for disinfection regimes. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Metabonomics study on Polygonum multiflorum induced liver toxicity in rats by GC-MS
Zhang, Yuan; Wang, Nannan; Zhang, Meiling; Diao, Tingting; Tang, Jingyue; Dai, Mingzhu; Chen, Suhong; Lin, Guanyang
2015-01-01
Polygonum multiflorum, a traditional Chinese medicinal herb, is widely used in liver and liver nourishing. Recent years, drug regulatory departments reported that Polygonum multiflorum caused serious adverse reaction in clinic, especially liver injury. In this study, we detected the changes in rat serum and liver tissue metabolites through gas chromatography-mass spectrometry (GC-MS). Mass spectrometry, partial least squares-discriminate analysis (PLS-DA) and other diversified techniques were used to analyze the differences among their metabolites. Compared to the control group, the serum concentrations of L-threonine and serine in water extraction groups increased. The serum concentrations of 9,12-octadecadienoic acid, hexadecanoic acid, oleic acid, D-glucose and octadecanoic acid in alcohol extraction groups increased, while lactic acid decreased to a great extent. For liver tissue, compared to the control group, the concentrations of myo-inositol, oleic acid and cholesterol in water extraction groups increased, while those of hexadecanoic acid, octadecanoic acid, ribitol and butanedioic acid decreased to a great extent. The concentrations of myo-inositol, phosphoric acid, uridine, oleic acid, cholesterol and butanoic acid in alcohol extraction groups increased to a great extent, while those of hexadecanoic acid, octadecanoic acid, ribitol and butanedioic acid decreased. The results indicate that Polygonum multiflorum induces the metabolic disorders of energy metabolism, amino acid and lipid metabolism. What’s more, liver injury of alcohol extraction group was more serious than group of water extraction. PMID:26379894
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Song, Yonghui; Dai, Yunrong; Hu, Qiong; Yu, Xiaohua; Qian, Feng
2014-04-01
P recovery from swine wastewater has become a great concern as a result of the high demand for P resources and its potential eutrophication effects on water ecosystems. The method of magnesium ammonium phosphate (MAP) crystallization was used to recover P from simulated swine wastewater, and the effects of three organic acids (citric acid, succinic acid and acetic acid) on P removal efficiency and rate at different pH values were investigated. The results indicated that the P removal efficiency was worst affected by citric acid in the optimal pH range of 9.0-10.5, followed by succinic acid and acetic acid, and the influencing extent of organic acids decreased with the increasing pH value. Due to the complexation between organic acid and Mg(2+)/NH4(+), all of three organic acids could inhibit the P removal rate at the beginning of the reaction, which showed positive correlation between the inhibition effects and the concentration of organic acids. The high concentration of citric acid could completely suppress the MAP crystallization reaction. Moreover, citric acid and succinic acid brought obvious effects on the morphology of the crystallized products. The experimental results also demonstrated that MAP crystals could be obtained in the presence of different kinds and concentrations of organic acids. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Acidic organic compounds in beverage, food, and feed production.
Quitmann, Hendrich; Fan, Rong; Czermak, Peter
2014-01-01
Organic acids and their derivatives are frequently used in beverage, food, and feed production. Acidic additives may act as buffers to regulate acidity, antioxidants, preservatives, flavor enhancers, and sequestrants. Beneficial effects on animal health and growth performance have been observed when using acidic substances as feed additives. Organic acids could be classified in groups according to their chemical structure. Each group of organic acids has its own specific properties and is used for different applications. Organic acids with low molecular weight (e.g. acetic acid, lactic acid, and citric acid), which are part of the primary metabolism, are often produced by fermentation. Others are produced more economically by chemical synthesis based on petrochemical raw materials on an industrial scale (e.g. formic acid, propionic and benzoic acid). Biotechnology-based production is of interest due to legislation, consumer demand for natural ingredients, and increasing environmental awareness. In the United States, for example, biocatalytically produced esters for food applications can be labeled as "natural," whereas identical conventional acid catalyst-based molecules cannot. Natural esters command a price several times that of non-natural esters. Biotechnological routes need to be optimized regarding raw materials and yield, microorganisms, and recovery methods. New bioprocesses are being developed for organic acids, which are at this time commercially produced by chemical synthesis. Moreover, new organic acids that could be produced with biotechnological methods are under investigation for food applications.
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Kimoto-Nira, Hiromi; Kobayashi, Miho; Nomura, Masaru; Sasaki, Keisuke; Suzuki, Chise
2009-05-31
Bile resistance is one of the basic characteristics of probiotic bacteria. The aim of this study was to investigate the characteristics of bile resistance in lactococci by studying the relationship between bile resistance and cellular fatty acid composition in lactococcci grown on different media. We determined the bile resistance of 14 strains in lactose-free M17 medium supplemented with either glucose only (GM17) or lactose only (LM17). Gas chromatographic analyses of free lipids extracted from the tested strains were used for determining their fatty acid composition. A correlation analysis of all strains grown in both media revealed significant positive correlations between bile resistance and relative contents of hexadecanoic acid and octadecenoic acid, and negative correlations between bile resistance and relative contents of hexadecenoic acid and C-19 cyclopropane fatty acid. It is also a fact that the fatty acids associated with bile resistance depended on species, strain, and/or growth medium. In L. lactis subsp. cremoris strains grown in GM17 medium, the bile-resistant strains had significantly more octadecenoic acid than the bile-sensitive strains. In LM17 medium, bile-resistant strains had significantly more octadecenoic acid and significantly less C-19 cyclopropane fatty acid than the bile-sensitive strains. In L. lactis subsp. lactis strains, bile resistances of some of the tested strains were altered by growth medium. Some strains were resistant to bile in GM17 medium but sensitive to bile in LM17 medium. Some strains were resistant in both media tested. The strains grown in GM17 medium had significantly more hexadecanoic acid and octadecenoic acid, and significantly less tetradecanoic acid, octadecadienoic acid and C-19 cyclopropane fatty acid than the strains grown in LM17 medium. In conclusion, the fatty acid compositions of the bile-resistant lactococci differed from those of the bile-sensitive ones. More importantly, our data suggest that altering their fatty acid composition (i.e. increased hexadecanoic acid and octadecenoic acid and decreased hexadecenoic acid and C-19 cyclopropane fatty acid) by changing growth conditions may be a useful way to enhance their bile resistance in lactococci.
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Lipid and fatty acid analysis of the Plodia interpunctella granulosis virus (PiGV) envelope
NASA Technical Reports Server (NTRS)
Shastri-Bhalla, K.; Funk, C. J.; Consigli, R. A.; Spooner, B. S. (Principal Investigator)
1993-01-01
Virus envelope was isolated from Plodia interpunctella granulosis virus, produced in early fourth-instar larvae. Both polar and neutral lipids were analyzed by two-dimensional thin-layer chromatography. Fatty acid composition of various individual neutral and polar lipids was determined by gas-liquid chromatography. The major components of envelope neutral lipid were diacylglycerols. Palmitic acid and stearic acid were the major saturated fatty acids in both polar and neutral lipids. Whereas palmitoleic acid was the major unsaturated fatty acids in neutral lipids, oleic acid was the major unsaturated fatty acid in the polar lipids.
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Oboh, Ganiyu; Agunloye, Odunayo M; Akinyemi, Ayodele J; Ademiluyi, Adedayo O; Adefegha, Stephen A
2013-02-01
This study sought to investigate and compare the interaction of caffeic acid and chlorogenic acid on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and some pro-oxidants (FeSO(4), sodium nitroprusside and quinolinic acid) induced oxidative stress in rat brain in vitro. The result revealed that caffeic acid and chlorogenic acid inhibited AChE and BChE activities in dose-dependent manner; however, caffeic acid had a higher inhibitory effect on AChE and BChE activities than chlorogenic acid. Combination of the phenolic acids inhibited AChE and BChE activities antagonistically. Furthermore, pro-oxidants such as, FeSO(4), sodium nitroprusside and quinolinic acid caused increase in the malondialdehyde (MDA) contents of the brain which was significantly decreased dose-dependently by the phenolic acids. Inhibition of AChE and BChE activities slows down acetylcholine and butyrylcholine breakdown in the brain. Therefore, one possible mechanism through which the phenolic acids exert their neuroprotective properties is by inhibiting AChE and BChE activities as well as preventing oxidative stress-induced neurodegeneration. However, esterification of caffeic acid with quinic acid producing chlorogenic acid affects these neuroprotective properties.
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Effects of aerosol formulation to amino acids and fatty acids contents in Haruan extract.
Febriyenti; Bai-Baie, Saringat Bin; Laila, Lia
2012-01-01
Haruan (Channa striatus) extract was formulated to aerosol for wound and burn treatment. Haruan extract is containing amino acids and fatty acids that important for wound healing process. The purpose of this study is to observe the effect of formulation and other excipients in the formula to amino acids and fatty acids content in Haruan extract before and after formulated into aerosol. Precolumn derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) method is used for amino acids analysis. Fatty acids in Haruan extract were esterified using transesterification method to form FAMEs before analyzed using GC. Boron trifluoride-methanol reagent is used for transesterification. Tyrosine and methionine concentrations were different after formulated. The concentrations were decrease. There are six fatty acids have amount that significantly different after formulated into concentrate and aerosol. Contents of these fatty acids were increase. Generally, fatty acids which had content increased after formulated were the long-chain fatty acids. This might be happen because of chain extension process. Saponification and decarboxylation would give the chain extended product. Therefore contents of long-chain fatty acids were increase. Generally, the aerosol formulation did not affect the amino acids concentrations in Haruan extract while some long-chain fatty acids concentrations were increase after formulated into concentrate and aerosol.
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Le-Bail, P; Lorentz, C; Pencreac'h, G; Soultani-Vigneron, S; Pontoire, B; López Giraldo, L J; Villeneuve, P; Hendrickx, J; Tran, V
2015-03-06
5-Caffeoylquinic acid (chlorogenic acid), is classified in acid-phenols family and as polyphenolic compounds it possesses antioxidant activity. The oxydative modification of chlorogenic acid in foods may lead to alteration of their qualities; to counteract these degradation effects, molecular encapsulation was used to protect chlorogenic acid. Amylose can interact strongly with a number of small molecules, including lipids. In order to enable chlorogenic acid complexation by amylose, a C16 aliphatic chain was previously grafted onto the cycle of quinic acid. This work showed that for the two lipophilic derivatives of chlorogenic acid: hexadecyl chlorogenate obtained by alkylation and 3-O-palmitoyl chlorogenic acid obtained by acylation; only the 3-O-palmitoyl chlorogenic acid complexed amylose. The chlorogenic acid derivatives were studied by X-ray diffraction, differential scanning calorimetry and NMR to elucidate the interaction. By comparing the results with previous work on the complexation of amylose by 4-O-palmitoyl chlorogenic acid, the importance of the aliphatic chain position on the cycle of the quinic acid is clearly highlighted. A study in molecular modeling helped to understand the difference in behavior relative to amylose of these three derivatives of chlorogenic acid. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Tanaka, Hideko; Harauma, Akiko; Takimoto, Mao; Moriguchi, Toru
2015-06-01
In our previously study, we reported lower tear volume in with an n-3 fatty acid deficient mice and that the docosahexaenoic acid and total n-3 fatty acid levels in these mice are significantly reduced in the meibomian gland, which secretes an oily tear product. Furthermore, we noted very long chain fatty acids (≥25 carbons) in the meibomian gland. To verify the detailed mechanism of the low tear volume in the n-3 fatty acid-deficient mice, we identified the very long chain fatty acids in the meibomian gland, measured the fatty acid composition in the tear product. Very long chain fatty acids were found to exist as monoesters. In particular, very long chain fatty acids with 25-29 carbons existed for the most part as iso or anteiso branched-chain fatty acids. n-3 fatty acid deficiency was decreased the amount of meibum secretion from meibomian gland without change of fatty acid composition. These results suggest that the n-3 fatty acid deficiency causes the enhancement of evaporation of tear film by reducing oily tear secretion along with the decrease of meibomian gland function. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Mastelić, Josip; Politeo, Olivera; Jerković, Igor
2008-04-07
The essential oil of Helichrysum italicum (Roth) G. Don (everlasting or Immortelle essential oil) was isolated by hydrodistillation and analysed by GC and GCMS. Forty four compounds were identified. The main components were alpha-pinene(12.8%), 2-methyl-cyclohexyl pentanoate (11.1 %), neryl acetate (10.4%), 1,7-di-epi-alpha-cedrene (6.8%) and other compounds. The oil was fractionated and ester-containing fraction was hydrolysed with KOH/H(2)SO(4). The liberated volatiles were analysed by GC and GC-MS: three phenols and twenty seven volatile carboxylic acids were identified[70% low fatty acids (C(2)-C(5)), 15% C(10)-C(12) acids and 15% other acids]. The main acids were acetic acid (24.3%) propanoic acid (17.2%), 2-methylpropanoic acid (11.4%),dodecanoic acid (8.7%), 2-methylbutanoic acid (8.3%), (Z)-2-methylbutenoic acid(5.1%) and decanoic acid (4.6%). With respect to the identified bonded carboxylic acids,the minimal number of esters in the oil was twenty seven, but their overall quantity was probably larger due to different possible combinations of alcohols with acids to form esters. On the other hand, only six main esters were identified in the oil before fractionation and hydrolysis.
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Pyridine metabolism in tea plants: salvage, conjugate formation and catabolism.
Ashihara, Hiroshi; Deng, Wei-Wei
2012-11-01
Pyridine compounds, including nicotinic acid and nicotinamide, are key metabolites of both the salvage pathway for NAD and the biosynthesis of related secondary compounds. We examined the in situ metabolic fate of [carbonyl-(14)C]nicotinamide, [2-(14)C]nicotinic acid and [carboxyl-(14)C]nicotinic acid riboside in tissue segments of tea (Camellia sinensis) plants, and determined the activity of enzymes involved in pyridine metabolism in protein extracts from young tea leaves. Exogenously supplied (14)C-labelled nicotinamide was readily converted to nicotinic acid, and some nicotinic acid was salvaged to nicotinic acid mononucleotide and then utilized for the synthesis of NAD and NADP. The nicotinic acid riboside salvage pathway discovered recently in mungbean cotyledons is also operative in tea leaves. Nicotinic acid was converted to nicotinic acid N-glucoside, but not to trigonelline (N-methylnicotinic acid), in any part of tea seedlings. Active catabolism of nicotinic acid was observed in tea leaves. The fate of [2-(14)C]nicotinic acid indicates that glutaric acid is a major catabolite of nicotinic acid; it was further metabolised, and carbon atoms were finally released as CO(2). The catabolic pathway observed in tea leaves appears to start with the nicotinic acid N-glucoside formation; this pathway differs from catabolic pathways observed in microorganisms. Profiles of pyridine metabolism in tea plants are discussed.
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Huang, Yang; Wilson, Mark; Chapman, Belinda; Hocking, Ailsa D
2010-02-01
The potential efficacy of four weak acids as preservatives in low-acid intermediate moisture foods was assessed using a glycerol based agar medium. The minimum inhibitory concentrations (MIC, % wt./wt.) of each acid was determined at two pH values (pH 5.0, pH 6.0) and two a(w) values (0.85, 0.90) for five food spoilage fungi, Eurotium herbariorum, Eurotium rubrum, Aspergillus niger, Aspergillus flavus and Penicillium roqueforti. Sorbic acid, a preservative commonly used to control fungal growth in low-acid intermediate moisture foods, was included as a reference. The MIC values of the four acids were lower at pH 5.0 than pH 6.0 at equivalent a(w) values, and lower at 0.85 a(w) than 0.90 a(w) at equivalent pH values. By comparison with the MIC values of sorbic acid, those of caprylic acid and dehydroacetic acid were generally lower, whereas those for caproic acid were generally higher. No general observation could be made in the case of capric acid. The antifungal activities of all five weak acids appeared related not only to the undissociated form, but also the dissociated form, of each acid.
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Guo, Rui; Reiner, Eric J; Bhavsar, Satyendra P; Helm, Paul A; Mabury, Scott A; Braekevelt, Eric; Tittlemier, Sheryl A
2012-11-01
A comprehensive method to extract perfluoroalkyl carboxylic acids, perfluoroalkane sulfonic acids, perfluoroalkyl phosphonic acids, perfluoroalkyl phosphinic acids, and polyfluoroalkyl phosphoric acid diesters simultaneously from fish samples has been developed. The recoveries of target compounds ranged from 78 % to 121 %. The new method was used to analyze lake trout (Salvelinus namaycush) from the Great Lakes region. The results showed that the total perfluoroalkane sulfonate concentrations ranged from 0.1 to 145 ng/g (wet weight) with perfluorooctane sulfonate (PFOS) as the dominant contaminant. Concentrations in fish between lakes were in the order of Lakes Ontario ≈ Erie > Huron > Superior ≈ Nipigon. The total perfluoroalkyl carboxylic acid concentrations ranged from 0.2 to 18.2 ng/g wet weight. The aggregate mean perfluorooctanoic acid (PFOA) concentration in fish across all lakes was 0.045 ± 0.023 ng/g. Mean concentrations of PFOA were not significantly different (p > 0.1) among the five lakes. Perfluoroalkyl phosphinic acids were detected in lake trout from Lake Ontario, Lake Erie, and Lake Huron with concentration ranging from non-detect (ND) to 0.032 ng/g. Polyfluoroalkyl phosphoric acid diesters were detected only in lake trout from Lake Huron, at levels similar to perfluorooctanoic acid.
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Singh-Blom, Amrita; Hughes, Randall A; Ellington, Andrew D
2014-05-20
Residue-specific incorporation of non-canonical amino acids into proteins is usually performed in vivo using amino acid auxotrophic strains and replacing the natural amino acid with an unnatural amino acid analog. Herein, we present an efficient amino acid depleted cell-free protein synthesis system that can be used to study residue-specific replacement of a natural amino acid by an unnatural amino acid analog. This system combines a simple methodology and high protein expression titers with a high-efficiency analog substitution into a target protein. To demonstrate the productivity and efficacy of a cell-free synthesis system for residue-specific incorporation of unnatural amino acids in vitro, we use this system to show that 5-fluorotryptophan and 6-fluorotryptophan substituted streptavidin retain the ability to bind biotin despite protein-wide replacement of a natural amino acid for the amino acid analog. We envisage this amino acid depleted cell-free synthesis system being an economical and convenient format for the high-throughput screening of a myriad of amino acid analogs with a variety of protein targets for the study and functional characterization of proteins substituted with unnatural amino acids when compared to the currently employed in vivo methodologies. Copyright © 2014 Elsevier B.V. All rights reserved.
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Amylolytic bacterial lactic acid fermentation - a review.
Reddy, Gopal; Altaf, Md; Naveena, B J; Venkateshwar, M; Kumar, E Vijay
2008-01-01
Lactic acid, an enigmatic chemical has wide applications in food, pharmaceutical, leather, textile industries and as chemical feed stock. Novel applications in synthesis of biodegradable plastics have increased the demand for lactic acid. Microbial fermentations are preferred over chemical synthesis of lactic acid due to various factors. Refined sugars, though costly, are the choice substrates for lactic acid production using Lactobacillus sps. Complex natural starchy raw materials used for production of lactic acid involve pretreatment by gelatinization and liquefaction followed by enzymatic saccharification to glucose and subsequent conversion of glucose to lactic acid by Lactobacillus fermentation. Direct conversion of starchy biomass to lactic acid by bacteria possessing both amylolytic and lactic acid producing character will eliminate the two step process to make it economical. Very few amylolytic lactic acid bacteria with high potential to produce lactic acid at high substrate concentrations are reported till date. In this view, a search has been made for various amylolytic LAB involved in production of lactic acid and utilization of cheaply available renewable agricultural starchy biomass. Lactobacillus amylophilus GV6 is an efficient and widely studied amylolytic lactic acid producing bacteria capable of utilizing inexpensive carbon and nitrogen substrates with high lactic acid production efficiency. This is the first review on amylolytic bacterial lactic acid fermentations till date.
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Monette, M.Y.; Bjornsson, Bjorn Thrandur; McCormick, S.D.
2008-01-01
Episodic acidification resulting in increased acidity and inorganic aluminum (Ali) is known to interfere with the parr-smolt transformation of Atlantic salmon (Salmo salar), and has been implicated as a possible cause of population decline. To determine the extent and mechanism(s) by which short-term acid/Al exposure compromises smolt development, Atlantic salmon smolts were exposed to either control (pH 6.7-6.9) or acid/Al (pH 5.4-6.3, 28-64 ??g l-1 Ali) conditions for 2 and 5 days, and impacts on freshwater (FW) ion regulation, seawater (SW) tolerance, plasma hormone levels and stress response were examined. Gill Al concentrations were elevated in all smolts exposed to acid/Al relative to controls confirming exposure to increased Ali. There was no effect of acid/Al on plasma ion concentrations in FW however, smolts exposed to acid/Al followed by a 24 h SW challenge exhibited greater plasma Cl- levels than controls, indicating reduced SW tolerance. Loss of SW tolerance was accompanied by reductions in gill Na+,K+-ATPase (NKA) activity and Na+,K+,2Cl- (NKCC) cotransporter protein abundance. Acid/Al exposure resulted in decreased plasma insulin-like growth factor (IGF-I) and 3,3???,5???-triiodo-l-thyronine (T3) levels, whereas no effect of treatment was seen on plasma cortisol, growth hormone (GH), or thyroxine (T4) levels. Acid/Al exposure resulted in increased hematocrit and plasma glucose levels in FW, but both returned to control levels after 24 h in SW. The results indicate that smolt development and SW tolerance are compromised by short-term exposure to acid/Al in the absence of detectable impacts on FW ion regulation. Loss of SW tolerance during short-term acid/Al exposure likely results from reductions in gill NKA and NKCC, possibly mediated by decreases in plasma IGF-I and T3. ?? 2008 Elsevier Inc.
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Fatty acid profile of Albizia lebbeck and Albizia saman seed oils: Presence of coronaric acid
USDA-ARS?s Scientific Manuscript database
In this work, the fatty acid profiles of the seed oils of Albizia lebbeck and Albizia saman (Samanea saman) are reported. The oils were analyzed by GC, GC-MS, and NMR. The most prominent fatty acid in both oils is linoleic acid (30-40%), followed by palmitic acid and oleic acid for A. lebbeck and ol...
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21 CFR 172.856 - Propylene glycol mono- and diesters of fats and fatty acids.
Code of Federal Regulations, 2010 CFR
2010-04-01
... fatty acids. 172.856 Section 172.856 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... diesters of fats and fatty acids. Propylene glycol mono- and diesters of fats and fatty acids may be safely... and/or fatty acids in compliance with § 172.860 and/or oleic acid derived from tall oil fatty acids in...
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Corrosion-Resistant Alkyd Coatings
1992-02-18
molecule. Examples of such acid compounds include the aliphatic saturated dibasic acids such as succinic acid , adipic acid , azelaic acid , sebacic...of a benzoic acid . 15. SUBJECT TERMS corrosion control, single topcoat, one coat 16. SECURITY CLASSIFICATION OF: unclassified a. REPORT...consisting essentially of critical amounts of at least one zinc phos- phate, zinc molybdate and at least one zinc salt of a benzoic acid . 15
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Method of increasing conversion of a fatty acid to its corresponding dicarboxylic acid
Craft, David L.; Wilson, C. Ron; Eirich, Dudley; Zhang, Yeyan
2004-09-14
A nucleic acid sequence including a CYP promoter operably linked to nucleic acid encoding a heterologous protein is provided to increase transcription of the nucleic acid. Expression vectors and host cells containing the nucleic acid sequence are also provided. The methods and compositions described herein are especially useful in the production of polycarboxylic acids by yeast cells.