Effect Of Sodium Taurocholate Research Articles

Effect of Sodium Taurocholate on Aggregation Behavior of Amphiphilic Drug Solution

AbstractThe aggregation behavior of promazine hydrochloride (PMZ) and bile salt (sodium taurocholate (NaTC)) mixtures at various compositions and temperature in pure and mixed states were studied using conductometry technique in aqueous solutions. The values of experimental and ideal critical micelle concentration (cmc and cmcid) propose attractive interactions in PMZ-NaTC mixtures. By applying the regular solution theory (RST) various physicochemical parameter such as micellar mole fraction in the mixed (X1) and ideal (X1id) state, interaction parameters (β), thermodynamic parameters of micellization as well as other related parameters have been evaluated and discussed in detail. The results show that the synergistic effect between drug and bile salt plays a crucial role in the redtdprefuction of the overall cmc value in aqueous solution at various composition of NaTC. The thermodynamic parameters recommend the discharge of water from the hydrophobic part of the PMZ at higher temperatures.

Effect of Sodium Taurocholate on Omeprazole Buccal Adhesive Tablet: Physicochemical Characterization and Pharmacokinetics in Hamster

To formulate an omeprazole buccal adhesive tablet with improved bioavailability using sodium taurocholate, omeprazole buccal adhesive tablets were prepared with sodium alginate, HPMC, magnesium oxide and different quantities of sodium taurocholate. Their physicochemical properties, such as the mucoadhesive force, stability in human saliva and release, were examined. Moreover, the absolute bioavailability was assessed by comparing the buccal administration to an omeprazole solution given intravenously to hamsters. Sodium taurocholate barely influenced the mucoadhesive force of the tablets; however, it affected the drug stability in human saliva. It positively influenced the fast drug release, but did not affect the release mechanism. In particular, omeprazole buccal adhesive tablets [omeprazole/ sodium alginate/HPMC/magnesium oxide/sodium taurocholate (20/24/6/50/10 mg/tab)] showed an absolute bioavailability of about 30% in hamsters. They remained attached to the cheeks without disintegration. Moreover, they were stable in human saliva for at least 4 h. Thus, it was concluded that this omeprazole buccal adhesive tablet could be a useful possible commercial pharmaceutical product. Keywords: Absolute bioavailability, enhancer, mucoadhesive force, omeprazole buccal adhesive tablet, sodium taurocholate, stability in human saliva.

In Vitro Evaluation of Mucoadhesive Films for Gingival Administration of Lidocaine

The aim of this study was the optimization of a lidocaine-based film formulation for the prevention of pain from needle prick during the injection of local anesthetic in dentistry. Film performances were evaluated in vitro by studying lidocaine permeation across pig esophageal epithelium as model for nonkeratinized buccal mucosa. The results obtained showed that the molecular weight of the film-forming polymer had no effect on lidocaine transport. The introduction of the adhesive Plastoid® into the film determined a significant increase of drug permeation rate, which was further improved by the addition of Azone®. On the contrary, the effect of sodium taurocholate was negligible.

Effects of Sodium Taurocholate on the Absorption of Inhaled 99mTc-DTPA

The effects of a natural surface-active agent, sodium taurocholate (NaTC), on the absorption of a hydrophilic solute, technetium-99m-labelled diethylene triamine pentaacetic acid (99mTc-DTPA), deposited at various sites within the airways were evaluated in this open, cross-over, and single-dose study. Nine healthy non-smokers received 99mTc-DTPA with or without the addition of NaTC, administered as an oropharyngeal aerosol and as nebulized large and fine droplet-sized pulmonary aerosols delivered by Pari and UltraVent nebulizers inhaled at fairly rapid and slow flows, respectively. Plasma concentration versus time profiles and 24-h urinary excretion of radioactivity were assessed. Further, 99mTc-labelled human serum albumin nanocolloidal particles (99mTc-Nanocoll) were administered with or without NaTC by Pari and followed by repeated chest gamma-imaging. NaTC changed no pharmacokinetic parameters for oropharyngeal 99mTc-DTPA. Independent of intrapulmonary 99mTc-DTPA deposition pattern, NaTC reduced Tmax (Pari: -0.8 h; UltraVent: -1.5 h) and mean absorption time (MAT) (-0.4 h; -0.7 h), and increased bioavailability (+13%; +44%) and dose-adjusted Cmax (+54%; +103%). NaTC decreased the pulmonary 99mTc-Nanocoll disappearance half-life from 8 h and 45 min to 4 h and 19 min. Our findings suggest that NaTC increases both rate and extent of 99mTc-DTPA absorption throughout the lower airways, without changing 99mTc-DTPA absorption in the oral cavity.

The effect of various liposome formulations on insulin penetration across Caco-2 cell monolayer

The aim of the study was to determine the penetration properties of various insulin containing liposome formulations through Caco-2 cell monolayer and to compare the in vitro test results with in vivo tests. The effect of sodium taurocholate as a penetration enhancer when it was added to the liposome formulation was also investigated. In vitro permeation experiments were performed in diffusion cells with the Caco-2 cell monolayer used as the membrane. Permeability values of various insulin containing liposome formulations through Caco-2 cells were determined (log k insulin-solution = −2.217 ± 0.0723 cm.h −1, log k insulin-liposome = −2.141 ± 0.0625 cm.h −1, log k insulin-sodium tauroholate liposome= −1.952 ± 0.0623 cm.h −1). In vivo tests were performed in mice. Formulations were administered orally and blood glucose levels were determined and penetrations were compared with the Caco-2 cell experiment results. In conclusion, the permeability of insulin was increased across Caco-2 cell monolayer when the liposome sodium taurocholate (NaTC) formulation was used. The oral administration of insulin and NaTC incorporated liposomes significantly decreased blood glucose levels. Furthermore, it was shown that a high in vitro/in vivo correlation was observed using the Caco-2 cell monolayer model.

Mechanisms for absorption enhancement of inhaled insulin by sodium taurocholate

The effects of sodium taurocholate (NaTC) on the absorption of inhaled insulin was investigated using both in vivo and in vitro experiments. The absolute bioavailability of insulin when given as a nebulized solution (0.6 mM) to anesthetized intubated beagle dogs was low (2.6±0.3%). However, when NaTC at different concentrations (2–32 mM) were included in the formulations the bioavailability increased and at 32 mM it was about nine times higher (23.2±4.4%) than for pure insulin. In a similar concentration interval (20–25 mM) NaTC decreased the transepithelial electrical resistance (TEER) across Caco-2 cell monolayers leading to an increased permeability of insulin. At higher concentrations (above 30 mM) the viability of the Caco-2 cells decreased and the insulin permeability increased dramatically. Furthermore, we show that NaTC in the concentration range 2–15 mM gradually decreases the aggregation state of insulin, i.e., produces mono- or dimeric insulin from hexameric insulin. In conclusion, NaTC increases the bioavailability of nebulized insulin, increases the permeability of insulin across Caco-2 cell monolayers, and decreases the aggregation state of insulin at similar concentrations. We suggest that the main mechanisms behind the absorption enhancement of inhaled insulin by NaTC are the production of insulin monomers and an opening of tight junctions between adjacent airway epithelial cells.

Effect of Different Bile Salts on the Relative Hypoglycemia of Witepsol W35 Suppositories Containing Insulin in Diabetic Beagle Dogs

Insulin suppositories were formulated using Witepsol W35 as a base to investigate the effect of various bile salts/acids on the plasma glucose concentration of diabetic beagle dogs. Comparison of the effect of these formulations was made with that produced by insulin subcutaneous injections. Of the bile salts/acids studied, incorporation of 100 mg of deoxycholic acid (DCA), sodium cholate (NaC), or sodium deoxycholate (NaDC) with insulin (10 U/Kg) showed that suppositories containing NaDC produced the highest area under the curve (AUC) and relative hypoglycemia (RH) of 290 ± 83 mg%h and 28% ± 8.1%, respectively. To study the optimum amount of NaDC in insulin suppositories to produce the highest RH, 50–200 mg/suppository were used, and we found that 150 mg NaDC produced 35% ± 13% RH. We also studied the influence of different doses of insulin (5–20 U/kg) in the presence of NaDC (100 mg). It was found that increase of the insulin dose was accompanied by an increase in AUC and maximum reduction in plasma glucose level Cmax. A combination of NaDC (100 mg) and NaC (50 mg) produced an AUC of 252 ± 13 mg% h and an RH of 49% ± 2.6%, which were higher than produced by either of its individual components (NaC 50 mg or NaDC 100 mg) when used alone or when compared with an equivalent amount of NaDC (150 mg). When the effect of sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC) was studied, it was found that an insulin suppository containing 100 mg of either NaTC or NaTDC produced an RH equivalent to that produced previously with a mixture of NaDC (100 mg) and NaC (50 mg). On the other hand, NaC (50 mg) did not improve the hypoglycemic effect of NaTC any further. In conclusion, a relative hypoglycemia of about 50% can be reached using insulin suppositories containing Witepsol W35 as a base and NaDC plus NaC (100 mg plus 50 mg, respectively), NaTDC (100 mg), or NaTC (100 mg) as rectal absorption enhancers of insulin. A desirable hypoglycemia, expressed as Cmax, and/or AUC can be reached by adjusting the insulin dose in the formulation according to the degree of hyperglycemia.

The effect of oral sodium taurocholate on endotoxemia and intestinal anastomotic wound healing in rats with obstructive jaundice.

The effect of sodium taurocholate (ST) on endotoxemia and intestinal anastomotic wound healing in obstructive jaundice was evaluated in a rat model. A total of 108 Wistar rats were divided into three main groups. Thus, 36 animals were given ileal anastomosis (IA) alone (IA group), 36 were given IA with bile duct ligation (BDL) (IA + BDL group), and 36 were given IA with BDL and oral sodium taurocholate (ST) (IA + BDL + ST group). These three main groups were then divided into three equal subgroups, A, B, and C, which were killed on postoperative days (POD) 3, 5, and 9, respectively. In the IA + BDL + ST group, ST was administrated perioperatively and ceased from POD 5 onwards. The anastomotic hydroxyproline level and bursting pressure were significantly lower in the IA + BDL animals compared with the others on POD 3, 5, and 9 (P < 0.008). Endotoxemia was prominent in the IA + BDL group from POD 3 (P = 0.011). After ST was stopped, 42% of the AI + BDL + ST animals developed endotoxemia by POD 9 (P = 0.008). Anastomotic wound healing was better in the IA + BDL + ST group (P < 0.01). These findings suggest that endotoxemia and its adverse effects on wound healing in obstructive jaundice can be prevented by the oral administration of ST.

Effect of Sodium Taurocholate on the In Vitro Growth of Lactobacilli

The effect on growth of a conjugated bile salt (sodium taurocholate) at physiological concentration was determined using cultures of Lactobacillus strains of murine origin. The bile salt stimulated the growth of one strain, did not affect the growth of another, but inhibited the growth of strains that produced relatively large amounts of the enzyme bile salt hydrolase. Comparison of the growth of isogenic strains that differed in the ability to produce bile salt hydrolase demonstrated that inhibition of growth was due to the accumulation of cholic acid in the culture medium as a result of the enzyme activity.

Acute pancreatitis in rats: effects of sodium taurocholate, CCK-8, and Sec on pancreatic microcirculation.

With use of in vivo microscopy, pancreatic duct permeability, red blood cell (RBC) velocities, functional capillary density (FCD), and overall changes in capillary blood flow (perfusion index) were estimated after intraductal infusion of sodium taurocholate (0.8 ml, 4%) alone or in combination with systemic administration of cholecystokinin (CCK, 0.3 microg/100 g body wt) or secretin (Sec, 10 microg/100 g body wt). Sodium taurocholate mediated a significant increase in pancreatic duct and capillary permeability within 105 +/- 26 s followed by a transient decrease in RBC velocities and a sustained decrease in FCD, which were paralleled by dramatic flow heterogeneity. Therefore, a significant reduction in overall capillary blood flow was calculated. CCK stimulation aggravated the microcirculatory failure due to a decrease in RBC velocities, which was accompanied by an increase in acinar cellular necrosis. Sec stimulation attenuated microcirculatory failure due to a more moderate reduction of FCD. The enhanced pancreatic duct and capillary permeability, which enables free diffusion of pancreatic digestive enzymes into the parenchyma, is the initiating event in acute biliary pancreatitis, causing microcirculatory failure and tissue damage. The microcirculatory changes are secondary and a propagating factor for the development of acini necrosis. Stimulation with CCK worsened the course of acute biliary pancreatitis.

The effect of sodium taurocholate on cholesteryl ester hydrolase in the rat lactating mammary gland

The effect of sodium taurocholate on cholesteryl ester hydrolase in the rat lactating mammary gland

Effect of bile acid on electrophysiological properties of rabbit sino-atrial node in vitro.

1 In order to examine the action of bile acid on cardiac pacemaker activity, the effect of sodium taurocholate (NTC) was studied on the membrane potential and current of rabbit sino-atrial node preparations by means of a double microelectrode voltage clamp technique. 2 In spontaneously beating sino-atrial node preparations, NTC (above 30 microM) decreased the maximum rate of rise of the action potential. Above 100 microM, the compound also exerted a bradycardiac effect and decreased the rate of diastolic depolarization significantly. 3 On the current systems, NTC produced dose-related decreases in the slow inward Ca2+ current and the time-dependent outward K+ current. 4 It is concluded that NTC depresses the spontaneous discharge of the sino-atrial node through decreases in both inward and outward current systems.

The effect of sodium taurocholate on proximal tubular reabsorption in the rat kidney.

Microperfusion of tubules in situ was used to study the direct effect of sodium taurocholate on reabsorption of fluid by the proximal tubule of the rat. Sodium taurocholate (0.1 mmol/l) in the tubular perfusate reduced proximal tubular fluid reabsorption by approximately 30%. Thus, the proximal tubule appears to be a major site at which bile salts cause a natriuresis in the rat, and possibly in obstructive jaundice in man.

Effect of sodium taurocholate on the human gastric mucosa at acid and neutral pH's

This study was conducted to determine whether taurocholate alters human gastric function and structure at a neutral pH, when ionized, and to contrast this with its effect at an acid intraluminal pH, when pronated. Five fasted healthy subjects were studied on 4 days in random order. Net ion fluxes, mucosal damage (as quantitated endoscopically), and potential difference were measured. The control solution instilled into the stomach in the first, third, and fourth 15-min periods contained 200 ml of 100 mM HCl, 54 mM mannitol, and [14C]polyethylene glycol. Taurocholate (10 mM) was added to the control solution (pH 1.1) or citrate buffer (pH 7.0) during the second 15-min period. The effect of citrate buffer alone or control solution alone was also tested. Because hydrogen and sodium fluxes could not be quantitated at pH 7 in the presence of citrate buffer, the net ion fluxes during the 15 min immediately after exposure to the test agent were measured. At both pH 1.1 and 7.0 taurocholate produced similar and significant increases in net hydrogen ion flux (−1.7 ± 0.4 and −1.8 ± 0.3 mmol/15 min, respectively), net sodium ion flux (1.8 ± 0.4 and 1.7 ± 0.2 mmol/15 min, respectively), decreases in potential difference, and mucosal erosions. The net hydrogen ion fluxes were significantly greater than occurred after citrate buffer alone or the HCl control. The net sodium fluxes after taurocholate in citrate were significantly greater than the pH 1.1 acid control, but not citrate buffer alone. These findings indicate that pronated (pH 1.1) or ionized (pH 7.0) taurocholate significantly damaged the in vivo human gastric mucosa. Taurocholate at pH 7 could in part be responsible for the gastric mucosal injury that occurs in patients with bile reflux gastritis.

Effect of sodium taurocholate on secretion by amphibian gastric mucosa in vitro.

Effects of sodium taurocholate on the electrical and secretory activity of amphibian gastric mucosa have been studied in vitro. Exposure of the luminal surface of fundic mucosa to high concentrations (5 X 10(-2) M) at low pH (2.0 and 3.0) produced a marked fall in potential difference and electrical resistance. At lower concentrations (10(-3) to 10(-4) M) and higher pH (7.4), taurocholate did not alter the electrical properties but significantly increased net acidification from 1.39 +/- 0.27 to 2.01 +/- 0.18 mueq . cm-2 . h-1 (means +/- SE; P less than 0.01). Pretreatment of fundic mucosa with cimetidine resulted in net alkaline secretion (0.27 +/- 0.07 mueq . cm-2 . h-1), and addition of taurocholate (10(-4) M) to the luminal surface at pH 7.4 converted net alkalinization to net acidification (0.94 +/- 0.28 mueq . cm-2 . h-1). This response was not inhibited by atropine (10(-5) M) or somatostatin (10(-6) M) but exhibited marked tachyphylaxis. Taurocholate (10(-4) M) inhibited alkaline secretion in thiocyanate-treated fundic mucosa (0.63 +/- 0.04 to 0.14 +/- 0.09 mueq . cm-2 . h-1; P less than 0.001) and in spontaneously alkaline-secreting antral mucosa (0.36 +/- 0.12 to 0.09 +/- 0.06 mueq . cm-2 . h-1; P less than 0.05), but acidification did not occur. Apparent stimulation of acid secretion and simultaneous inhibition of alkaline secretion of sodium taurocholate may play a role in the pathogenesis of mucosal damage by bile.

Gaucherʼs Disease II. Studies on the Kinetics of β-Glucosidase and the Effects of Sodium Taurocholate in Normal and Gaucher Tissues

Gaucherʼs Disease II. Studies on the Kinetics of β-Glucosidase and the Effects of Sodium Taurocholate in Normal and Gaucher Tissues

Effect of sodium taurocholate and ethanol on hydrogen ion absorption in rabbit esophagus.

The effect of sodium taurocholate (NaTC) (5 mM) and ethanol (5%) on H+ absorption by the esophagus was studied duringin vivo perfusion of rabbit esophagus with solutions of graded concentration of H+ containing either one of these agents. Net ion and volume fluxes, changes in osmolality and PD, histological change, absorption of NaTC or ethanol, were correlated with concentration of acid in the perfusate. There was linear correlation between H+ efflux and luminal H+ concentration except for experiments with NaTC at H+ concentrations higher than 100 mM. Both NaTC and ethanol caused greatly increased rate of removal of H+ from the lumen (accompanied by fall in PD), increased transport of other ions in the direction of their chemical gradients, and much structural disintegration. These changes were more severe with NaTC than with ethanol. In neutral solutions NaTC did not cause changes in PD or net ion fluxes, while ethanol depressed PD and increased net ion fluxes to a lesser extent than when acid was present. NaTC was not absorbed in a neutral solution but absorption increased with acidity. Acidity did not affect ethanol absorption. These data suggest that increased permeability of the esophageal mucosa is the basic mechanism underlying esophagitis. Increased permeability is related to absorption of NaTC or ethanol. The synergistic action of bile or alcohol and acid on the esophageal mucosa is compared to that of aspirin/acid on the gastric mucosa.

The Effect of Sodium Taurocholate on Biliary Iodipamide Excretion in the Dog

The effect of sodium taurocholate in stepwise increasing infusion rates, 0.3 to 9.6 mumoles per min per kg, on the biliary excretion rate of iodipamide was investigated in 6 dogs (10 experiments) with complete bile diversion under general anesthesia. Iodipamide was administered intravenously with an initial priming dose of 33 mumoles per kg followed by a constant infusion of 1.3 mumoles per min per kg. Although the bile flow continuously increased with an increasing taurocholate dose, the iodipamide excretion rate reached a plateau with a 0.6 mumoles per min per kg of taurcholate infusion, which was 20% higher than with the lowest taurocholate dose. With a taurocholate dose over 2.4 mumoles per min per kg, a significant decrease in the iodipamide rate was found, amounting to 22% of its maximum value with the largest taurocholate dose. The bile iodipamide concentration was already at its maximum with the lowest taurocholate dose, and it decreased with an increasing taurocholate dose. Since the bile iodipamide concentration is probably the most important determinant in clinical cholangiography, low bile salt plasma levels should result in the best radiographic visualization of the biliary tree.

The effect of sodium taurocholate on the permeability of antral and fundic gastric mucosa

The effect of sodium taurocholate on the permeability of antral and fundic gastric mucosae was investigated by using an in vitro preparation of rabbit antral and fundic gastric mucosae mounted in Ussing chambers and perfused with a physiological bicarbonate solution at 37°C. Permeability was measured by the transmucosal flux of [ 14C]erythritol, a water-soluble, nonlipid-soluble molecule. Twenty millimolar sodium taurocholate at pH 7.4 in the mucosal solution did not increase the flux of erythritol across fundic tissue when compared to controls but did cause a significant fall in tissue resistance, whereas 20 m M sodium taurocholate at pH 7.4 in the mucosal solution of antral tissue increased the flux of erythritol after 30 min when compared with controls, 2.23 ± 0.43 and 0.68 ± 0.14 pmol/cm 2/sec, respectively, and caused a statistically significant fall in tissue resistance. At pH 2.5 2 m M sodium taurocholate in the mucosal solution increased the flux of erythritol across fundic tissue when compared with controls, 5.73 ± 1.03 and 0.82 ± 0.15 pmol/cm 2/sec, respectively, and statistically reduced tissue resistance. In antral tissue 2 m M sodium taurocholate at pH 2.5 increased erythritol flux across antral tissue when compared with controls, 13.97 ± 5.15 and 1.38 ± 0.34 pmol/cm 2/sec, respectively, and statistically reduced tissue resistance. In treated mucosa the slope of the regression of flux against time was significantly greater in antral than fundic tissue, indicating greater antral mucosal permeability. At both high and low pH the increase in physical permeability caused by taurocholate is greater in antral than fundic mucosa.

Alteration of the Physical Pathways Through the Gastric Mucosa by Sodium Taurocholate

The effect of sodium taurocholate (Tch) on gastric mucosal permeability was investigated using an in vitro preparation of rabbit fundic gastric mucosa mounted in an Ussing chamber, and perfused with a physiological solution at 37°C. The permeability was measured by the mucosal to serosal flux of [14C]erythritol, a water-soluble, non-lipidsoluble molecule. The flux rate of erythritol in normal tissue was 1.85 ± 0.25 pmoles per cm2 per sec. and was increased by 20 mM Tch in the mucosal solution at pH 7.0 and pH 3.0, to 5.46 ± 0.54, and 25.48 ± 4.71 pmoles per cm2 per sec, respectively, after 1 hr, demonstrating a pH-dependent effect. At pH 3.0, Tch in the mucosal solution at doses of 2.5, 5, and 10 mM increased the mucosal to serosal flux rate to 3.98 ± 1.29, 5.81 ± 1.37, and 13.52 ± 2.31 pmoles per cm2 per sec, respectively, after 1 hr, demonstrating a dose-related effect. There was no statistical difference between the mucosal to serosal flux of erythritol with 20 mM Tch in the mucosal or serosal solutions. The fluxes of [14C]mannitol and [14C]lactose were altered in a similar direction by Tch, but the absolute flux of these substances was less than that of erythritol because of the larger size of the molecule. It is suggested that Tch causes an increase in permeability of the gastric mucosa through water-filled channels, which may be responsible for the increased transmucosal flux of hydrogen and sodium ions caused by bile salts.