Amounts Of Bile Salts Research Articles

Design and Synthesis of Newly Synthesized Acrylamide Derivatives as Potential Chemotherapeutic Agents against MCF-7 Breast Cancer Cell Line Lodged on PEGylated Bilosomal Nano-Vesicles for Improving Cytotoxic Activity.

Cancer is a multifaceted disease. With the development of multi drug resistance, the need for the arousal of novel targets in order to avoid these drawbacks increased. A new series of acrylamide derivatives was synthesized from starting material 4-(furan-2-ylmethylene)-2-(3,4,5-trimethoxyphenyl)oxazol-5(4H)–one (1), and they are evaluated for their inhibitory activity against β-tubulin polymerization. The target molecules 2–5 d were screened for their cytotoxic activity against breast cancer MCF-7 cell line. The results of cytotoxicity screening revealed that compounds 4e and 5d showed good cytotoxic profile against MCF-7 cells. Compounds 4e produced significant reduction in cellular tubulin with excellent β-tubulin polymerization inhibition activity. In addition, compound 4e exhibited cytotoxic activity against MCF-7 cells by cell cycle arrest at pre-G1 and G2/M phases, as shown by DNA flow cytometry assay. Aiming to enhance the limited aqueous solubility and, hence, poor oral bioavailability of the prepared lead acrylamide molecule, 4e-charged PEGylated bilosomes were successfully fabricated via thin film hydration techniques as an attempt to improve these pitfalls. 23 full factorial designs were manipulated to examine the influence of formulation variables: types of bile salt including either sodium deoxy cholate (SDC) or sodium tauro cholate (STC), amount of bile salt (15 mg or 30 mg) and amount of DSPE–mPEG-2000 amount (25 mg or 50 mg) on the characteristics of the nanosystem. The F7 formula of entrapment efficiency (E.E% = 100 ± 5.6%), particle size (PS = 280.3 ± 15.4 nm) and zeta potential (ZP = −22.5 ± 3.4 mv) was picked as an optimum formula with a desirability value of 0.868. Moreover, prominent enhancement was observed at the compound’s cytotoxic activity (IC50 = 0.75 ± 0.03 µM) instead of (IC50 = 2.11 ± 0.19 µM) for the unformulated 4e after being included in the nano-PEGylated bilosomal system.

Why is glycocholic acid sodium salt better than deoxycholic acid sodium salt for the preparation of mixed micelle injections?

Classical mixed micelle systems make excellent parenteral drug carriers for lipophilic or poorly soluble drugs, but many formulations details are not fully understood and need further study. Thus, we constructed mixed micelle systems with lecithin and either glycocholic acid sodium salt or deoxycholic acid sodium salt in order to investigate the differences between the bile salts. Vitamin K1, a lipid‐soluble drug, was encapsulated in the mixed micelles, and the influence of bile salts on the quality and stability of the mixed micelle systems was analyzed. Both bile salts displayed similar profiles, and the amounts of bile salts used in formulating clear solutions did not differ. Mixed micelle systems formed from glycocholic acid sodium were physically stable at low pH levels (5.5), whereas those formed from deoxycholic acid required higher pH (>8.5). High pH levels hurt active pharmaceutical ingredients that are prone to hydrolytic and oxidative degradation. Hence, when mixed micelle systems formed from deoxycholic acid sodium were sterilized, unexpected chemical unstability occurred. Therefore, we conclude that glycocholic acid sodium salt is more suitable than deoxycholic acid sodium salt for the preparation of mixed micelle injections.

Evaluation of bilosomes as nanocarriers for transdermal delivery of tizanidine hydrochloride: in vitro and ex vivo optimization

Bilosomes were developed in order to investigate their efficacy as nanocarriers for transdermal delivery of Tizanidine HCl (TZN), a skeletal muscle relaxant with low oral bioavailability. Full factorial experimental design consisting of 27 combinations was generated to study the effects of surfactant type, surfactant-to-cholesterol ratio and the amount of bile salt on the entrapment efficiency (EE), the vesicle size (VS) and in vitro dissolution of the TZN-loaded bilosomes. The permeation through the stratum cornea was optimized with the vertical diffusion assembly using excised rat skin. The permeation parameters of the selected bilosomes were compared to the unformulated drug and it was shown that TZN-B24 exhibited the highest enhancement ratio (ER = 8.8).The optimal formula (TZN-B24) consisting of span 60 in a ratio with cholesterol of 1:1 and 20 mg of bile salt was obtained by employing the desirability function of Design-Expert® software. The mathematical model used for the optimization was validated by comparing the predicted values of the EE (82.3%) and the VS (165.8 nm) with the experimental values of EE = 84.42% and of VS = 161.95 nm. TZN-B24 displayed high zeta potential which contributed to its good stability. It was evident from the results of this study that incorporating TZN in bilosomes improved significantly its permeation through the skin barrier and thus bilosomes can offer a potential nanoplatform using the transdermal route to improve the bioavailability of the drug.

Effects of bile salts and divalent cations on the adsorption of norfloxacin by agricultural soils

The effects of bile salts (sodium cholate and sodium deoxycholate, 0–20 mmol/L), divalent cations (Ca2+, Mg2+, Cu2+ and Zn2+, 0–20 mmol/L) or pH (3.0–10.0) on the adsorption of norfloxacin by three selected soils (Paddy_H, Paddy_G and Red_J) were systematically studied. Soil adsorption of norfloxacin follows a pseudo second-order kinetics model, and the maximum adsorption capacity has been determined from the nonlinear fit of the Langmuir isotherm model to be 88.8, 88.1 and 63.0 μmol/g for the adsorption onto Paddy_H, Paddy_G and Red_J, respectively. The results indicate that norfloxacin has a high adsorption affinity for the agricultural soils tested and that the organic content of these soils have at least a slight influence on this adsorption. The adsorption of norfloxacin to soils was strongly dependent on pH and exhibited a maximum at approximately pH 6. The presence of divalent cations prominently suppressed the adsorption of norfloxacin by paddy soils, which followed an order of Cu2+ > Mg2+ > Ca2+ > Zn2+, and by red soil, which followed an order of Cu2+ > Zn2+ > Ca2+ > Mg2+. The adsorption of norfloxacin (by the soils studied) sharply decreased as the amount of bile salts was increased. For uncharged norfloxacin at environmentally relevant pH values, such factors as soil type, exogenous divalent cations and macromolecules significantly altered the environmental fate and transport of norfloxacin between aquatic and soil interfaces.

Comparison of <i>In Vitro</i> Binding of Bile Salt by Pectins from Various Sources

Binding of bile salts by dietary fiber is believed to promote their excretion and hence to reduce the serum cholesterol level in man and experimental animals. In this study, the binding efficiency of soluble pectin from various sources, i.e., apple, citrus and pomelo, was examined. Sodium deoxycholate and sodium cholate hydrate were used as a model to represent bile salt in human body. The binding efficiency was assayed by acid reaction, thin layer chromatography (TLC) and enzyme cycling method. The results demonstrated that enzyme cycling method was the most suitable for assaying the in-vitro binding of bile salts while the TLC was not very sensitive, i.e., low amount of bile salts cannot be detected by TLC. Excess pectin from binding test could also interfere the acid reaction method even though the centrifugation was used to remove the excess pectin. When the concentration of pectin was increased, the binding efficiency with sodium deoxycholate increased. However, at 1% w/w of pectin, the binding efficiency decreased. The exception is for pomelo pectin in which the binding efficiency increased when the pectin concentration increased. With sodium cholate hydrate, only slight difference in binding efficiency was observed for all types and concentrations of pectin. The results indicate that the ability to bind bile salts of pectin might be responsible for its hypocholesterolemic action observed in experimental animals and humans.

Biomimetic formation of crystalline bone-like apatite layers on spongy materials templated by bile salts aggregates

Since the trabecular bone exhibit sponge-like bicontinuity there is a growing interest in the synthesis of spongy-like sieves for the construction of bio-active implantable materials. Here, we propose a one step sol–gel method for the synthesis of bicontinuous pore silica materials using different bile salts aqueous mixtures as templates. The influences of the type and amount of bile salt on the synthesis processes are investigated and correlated with the final material morphology. As a final point, their structural properties are interrelated with their ability to induce a bone-like apatite layer in contact with simulated body fluid (SBF). We have confirmed that under specific template conditions, the synthesized material has an open bio-active macropore structure that is blanched in a 3D-disordered sponge-like network similar than those existed in trabecular bone.

Bile Increases Intestinal Lymphatic Drug Transport in the Fasted Rat

This study was conducted to determine the influence of (1) the source of recruited endogenous fatty acid (FA), and (2) bile on intestinal lymphatic transport of halofantrine (Hf) in fasted rats. Endogenous FA output in bile, and exogenous ((14)C radiolabeled) FA, endogenous FA, and Hf transport in mesenteric lymph were determined following administration of low dose lipid formulations containing either 4 or 40 mg of exogenous FA [oleic acid (OA)] and different amounts of bile salt (BS) and lysophosphatidylcholine (LPC) to fasted rats. Administration of 40 mg of OA recruited endogenous FA and Hf transport into intestinal lymph, whereas 4 mg OA did not. However, addition of BS to the 4-mg OA dose led to stimulation of endogenous FA recruitment into lymph and an increase in lymphatic transport of Hf and endogenous FA output in bile. Addition of LPC to the 4-mg OA dose (dispersed in BS) caused a substantial increase in endogenous FA transport in lymph; however, no coincident increase in either lymphatic transport of Hf or endogenous FA output in bile was observed. Biliary-derived endogenous FA has a higher propensity to support lymphatic transport of Hf compared to other sources of endogenous FA. The results suggest that this is related to the disparate trafficking of these alternate sources of endogenous FA within the enterocyte.

Bile salt and acid tolerance of Lactobacillus rhamnosus strains isolated from Parmigiano Reggiano cheese

This study aimed to compare phenotypic and genetic characteristics of Lactobacillus rhamnosus strains isolated at the end of the ripening of Parmigiano Reggiano cheese and to investigate an important prerequisite of probiotic interest, such as the capability to survive at low pH and in presence of bile salts. The use of API 50 CH, RAPD-PCR analysis and species-specific PCR allowed to ascertain the identity of 63 L. rhamnosus strains. Three L. rhamnosus strains isolated from Parmigiano Reggiano cheese, L. rhamnosus ATCC 7469 T and the commercial strain L. GG were assayed to estimate the resistance to various stress factors reproducing in vitro some conditions of the gastro-intestinal environment such as low pH and different amounts of bile salts and acids. The behaviour of almost all the tested strains isolated from Parmigiano Reggiano cheese resulted analogous to that showed by L. GG.

Separation and Quantitation of Low Amounts of Enzymatic Lipolysis Products Obtained in the Presence of High Triglyceride Concentrations

A method has been developed for the qualitative and quantitative determination of enzymatic lipolysis products in the presence of high triglyceride concentrations, using aminopropyl bonded silica cartridges and capillary gas chromatography. Two reactions are catalyzed in the presence of the Rhizopus javanicus lipase: hydrolysis of triglycerides to diglycerides, and diglycerides to monoglycerides. Lipids were extracted from the hydrolyzed olive oil emulsion and separated into fractions with aminopropyl bonded silica cartridges by means of sequential elution. The elution procedure was well characterized and optimized to obtain a maximum recovery and purity for each lipid fraction. Further analysis was done with capillary gas chromatography. The method is suitable to study the properties of lipases in vitro in the presence of high triglyceride concentrations and different amounts of bile salts. The expected inhibition of the fungal lipase by higher concentrations of bile salts, under physiological conditions, was limited.

Organization of phosphatidylcholine and bile salt in rodlike mixed micelles

Small-angle neutron scattering (SANS) of aqueous mixed colloids of the bile salts glycocholate or glycochenodeoxycholate with egg yolk phosphatidylcholine and mixtures of taurocholate with dipalmatoylphosphatidylcholine (DPPC) shows that all of these system form particles with rodlike morphology in parts of the concentration-composition phase map. The formation of rodlike mixed micelles thus is a general feature of the phosphatidylcholine-bile salt systems. The orientation of the phosphatidylcholine and bite salts in the rod-shaped mixed micelles is addressed by SANS measurements of the aqueous mixtures of taurocholate with DPPC and with DPPC with the choline methyls deuterated. The results are consistent with the phosphatidylcholine being arranged in the rod such that the long axis perpendicular to the axis of the rodlike particle. The amount of bile salt in the rods calculated from the small-angle neutron scattering assuming radial arrangement of phosphatidylcholine suggests that the bile salt is inserted with its long axis parallel to the rod axis. Comparison of the cross-sectional radius of gyration and contrast-weighted mass per unit length of the a=egg yolk phosphatidylcholine-bile salt mixtures with those from the DPPC-bile salt mixtures indicates that this arrangement of the two components is a general feature of these systems. 31 refs., 9 figs.,more » 5 tabs.« less

Reduction of Colonic Carcinogenesis by Wheat Bran Independent of Fecal Bile Acid Concentration<xref ref-type="fn" rid="FN1">2</xref>

It has been reported previously that populations with a decreased concentration of fecal bile acids have a lower incidence of colon cancer. We examined the importance of fecal bile acid dilution by wheat bran (WB) in inhibiting colonic tumorigenesis in an experimental animal model. Male F344 rats received oral doses of the colon carcinogen 1,2-dimethylhydrazine [CAS: 540-73-8] and were assigned randomly to groups fed one of four semipurified diets for 26 weeks. The diets were fiber-free (FF), 10% WB, FF + bile salts, or WB + bile salts. The amount of bile salts added was adjusted to produce a fecal bile acid concentration in the group fed WB + bile salts equal to that found in the FF groups. Fecal bile acid concentrations at 12 and 24 weeks in the WB + bile salts group were similar to those in the FF group. Gross and microscopic findings at necropsy revealed a reduced total number and multiplicity of colon tumors in both bran-fed groups. Although the fecal bile acid concentrations of the FF and WB + bile salts groups were equal, the latter showed a significant reduction in tumor yield.

Bile Salts: A Determinant of the Bile-Peritoneal Electrical Potential Difference in the Rat

The electrical potential difference (PD) between bile and peritoneal cavity of the rat was determined in order to obtain additional information concerning the mechanism of bile formation in this species. A significant negative PD (− 4.4 ± 0.6 mv) was measured in the basal state at a time when the rat was secreting normal amounts of bile salts. The intravenous administration of sodium dehydrocholate produced a significant increase in negative PD, bile salt concentration, bile salt output, and bile flow. When non-bile salt dependent canalicular secretion was studied by creating a biliary fistula, there was a marked fall in PD, bile salt concentration, and bile salt output, but only a modest decrease in bile flow. Although the genesis of the PD cannot be determined with certainty, these changes in electrical PD correlated best with changes in bile salt concentration; the PD fell toward zero when non-bile salt dependent canalicular secretion was predominant. If the measured PD reflects canalicular events, non-bile salt dependent canalicular secretion may be associated with zero PD in the rat.

Alterations in biliary lipids of mice during dehydrocholic acid feeding

Mice were fed a lithogenic diet consisting of Purina chow and 0.5% dehydrocholic acid (DHA group). Controls received Purina chow. Every 2 wk for 20 wk animals were killed, and biliary phospholipid, cholesterol, and bile salt concentrations were determined, as well as the extent of gallstone formation. With time there was a gradual, significant decline in the concentration and the relative composition of phospholipid in both groups compared with initial values. There was a significant increase in biliary cholesterol concentration and relative amount in the DHA group compared with the control. No significant differences were found in the relative amounts of bile salt or phospholipid between the two groups. Feeding DHA resulted in an increased concentration of bile salts and the sum of measured lipid compared with controls. After 8 wk, gallstones were found in approximately 60% of autopsied animals and correlated with increased cholesterol concentration. Our data support the hypothesis that there is a component of cholesterol secretion that may not be bile salt- or phospholipid-dependent. Our data also suggest that biliary phospholipid secretion decreases with age.

Phospholipids in human lithogenic gall bladder bile.

IN normal human bile, cholesterol is maintained in micellar solution by bile salts and phospholipids. Precipitation of cholesterol occurs when the amount of bile salts and phospholipids falls relative to cholesterol1. There is evidence that in the presence of cholelithiasis there is a drop in the biliary bile salt–phospholipid/cholesterol ratio and an increase in the dihydroxy to trihydroxy bile salt ratio2. Phospholipids have been studied in normal bile3,4, but there is little information on phospholipid changes in the bile of subjects with gallstones. The present study has been undertaken to determine whether there are quantitative or qualitative changes in the phospholipids of human lithogenic gall bladder bile.

Effect of Anoxic Anoxia on Bile Secretion in the Rat

SummaryNo significant difference was found in the amount of bile salts excreted by 6 bile fistula rats when exposed for 4-hour periods to decreased oxygen tension (63 mm and 53 mm Hg) as compared to control periods. There was a statistically significant increase in the volume output of urine as a result of exposure to simulated altitude. No correlation existed between the amount of bile salts and the volume of urine excreted.

Bile salt therapy in gall bladder disease

(1) 3 groups of patients with gall bladder disease are described. (2) The use of a low fat diet and large amounts of bile salts is advocated in the treatment of these cases. (3) In the group (13 cases) with the type of postcholecystectomy syndrome not due to organic obstruction, relief was obtained in most of the cases with this form of therapy. (4) In two other groups, i.e., those with stones and normally functioning gall bladders (14 cases) and those with chronic gall bladder disease in whom the gall bladder failed to visualize (11 cases) considerable relief from symptoms was also obtained. (5) In the cases in whom gastric hyperacidity was present atropin and alkalies were helpful adjuvants in the therapy. (6) In view of these results, the use of this mode of therapy in a larger group of cases seems advisable.

Observations on the Rate of Growth of B. Coli

1. The normal rate of growth of B. coli in peptone water at 37 C. 2. The effect of the age of the culture on the rate of growth. 3. The effect of crystal violet and brilliant green. 4. The rate of growth in various standard mediums. 5. The effect of varying amounts of bile salts. 6. The effect of varying amounts of peptone. 7. The effect of dipotassium phosphate. 8. The effect of Liebig' s beef extract.

EFFECT OF THE INJECTION OF BILE ON THE CIRCULATION

1. We have confirmed previous work which shows that the injection of bile increases the tone of the vagus nerve, and that this action can be abolished after the administration of atropine. 2. We have found that the amount of bile salts in a lethal dose of pig's bile for dog's will, if inejcted alone, produce neither a fall in blood pressure nor a slowing in rate. 3. We have found that the amount of pigment in a lethal dose of the bile will, if injected alone, cause death with slowing of the heart and lowering of blood pressure. 4. We have found that the bile pigment in combination with calcium or sodium is less toxic than uncombined pigment. 5. We have found that in experimentally produced jaundice the calcium content of the blood is increased, while that of the liver, muscle and brain are decreased. 6. We are of the opinion that increase in calcium in the blood is a protective mechanism against the circulating pigments of obstructive jaundice.

The Use of Lactose-Bile Medium in Water Analysis

The determination of intestinal bacteria as represented by Bacillus coli gives, when properly interpreted, a most valuable index of the quality of a water from a sanitary standpoint. Unfortunately the presumptive test with Smith solution, owing to the interference of other growths of bacteria has often proved to be misleading, especially in badly polluted waters. In a paper previously published,1 entitled A New Solution for the Presumptive Test for Bacillus coli, the author has described numerous experiments on the selective inhibiting effect upon the growth of bacteria by the various salts and their constituents found in the bile. By the use of bile media most species of bacteria other than B. coli are killed or restrained, thus allowing of the free action of the intestinal germs. The tests show that the cholic acid radical of the bile is the effective agent. This conclusion is important in that it admits of the use of sodium glycocholate as an inhibiting salt. In ox bile, which is the material most available, nearly all of the bile salt present is in the form of glycocholate. The experiments also show that good results are obtained only when an amount of bile salt is used equal to that present in undiluted ox bile but that further concentration is unnecessary. Liquid ox bile filtered after sterilization contains about no grams of solid matter per liter, of which about 90 grams consist of bile salts. This is an amount far in excess of that previously employed as a restraining agent but a lesser amount gives less efficient results. The liquid also contains albuminous matter equal in food value to the meat extract employed in the usual media. An undiluted bile solution sterilized when freshly drawn may be