• Biomedical Science Letters
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• v.19 no.2
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• pp.158-163
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• 2013

Cholestatic liver is associated with hepatic inflammation and elevated proinflammatory cytokines. Recent studies indicate that certain cytokines can modulate bile secretion. In the present study, we have examined the role of interleukin (IL-2) on the bile secretion by a combination of study models. To examine the relevance of IL-2 on bile secretion, the expression of IL-2 and IL-2 receptor (IL-2R) of isolated normal and bile duct ligated (BDL) rats cholangiocytes was first measured by RT-PCR. In BDL rats, the expression of IL-2 and IL-2R was significantly increased compared with normal rats. To study the effect of IL-2 on bile secretion, bile flow was measured in normal and BDL rats. At the level of cholangiocytes, secretory responses of isolated bile duct unit (IBDU)s were quantified by videomicroscopy. The administrations of IL-2 had no significant effect on basal bile secretion in normal and BDL rats. There was no significant effect of IL-2 on basal bile ductular secretion as evidenced by no significant difference in luminal area of the IBDUs perfusedwith 100 pM of IL-2 from those of albumin carrier control. However, the secretin-stimulated bile ductular secretion was significantly (P < 0.01) inhibited by $34{\pm}4%$ (normal, n = 12), $21{\pm}5.3%$ (BDL 2 wk, n = 12) and $15{\pm}5.2%$ (BDL 4 wk, n = 12) with the co-administration of IL-2. As with other cytokines, physiologically relevant concentration of IL-2 can significantly inhibit secretin-stimulated bile ductular secretion. These findings support the important roles of cytokines in modulating bile secretion and may contribute to the cholestasis seen in cholestatic liver diseases.

• The Korean Journal of Pharmacology
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• v.18 no.1
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• pp.43-54
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• 1982

Bile formation is a complex process comprised of three separate physiologic mechanism operating at two anatomical sites. At present time, it was known that at least two processes are responsible for total canalicular secretion at the bile canaliculus. One of the processes is bile salt-dependent secretion (BSDS) hypothesis that the active transport of bile salts from plasma to bile provided a primary stimulus for bile formation: the osmotic effect of actively transported bile acid was responsible for the movement of water and ions into bile. The other process is bile salt-independent secretion (ESIS), which is unrelated to bile salt secretion at the canaliculus and which may involve the active transport of sodium. The third process for bile formation involves the biliary ductal epithelium. Secretin-stimulated bile characteristically contained bicarbonate in high concentration. Therefor, it was suggested that secretin stimulated water and bicarbonate secretion from the biliary ductules. One the other hand, it was found that a large amounts of cAMP was present in canine bile but no apparent relationship between bile salt secretion and cAMP content in dog bile. However, bile flow studies in human have demonstrated that secretin and glucagon increase bile cAMP secretion as does secretin in baboons. Secretin increases baboon bile duct mucosal cAMP levels in addition to bile CAMP levels suggesting that in that species secretin-stimulated bile flow may be cAMP mediated. It has been postulated that glucagon and theophylline which increase the bile salt-independent secretion in dogs might act through an increased in liver cAMP content. In a few studies, the possible role of cAMP on bile formation has teen tested by administration of an exogenous derivative of cAMP, dibutyryl cAMP. In the rat, DB cAMP did not modify bile flow, but injection of DB cAMP in the dog promoted an increase in the bile salt-independent secretion. Because of these contradictory results, this study was carried out to examine the relationship between cyclic nucleotides and bile flow due to various bile salts as well as secretin or theophylline. Experiments were performed in rabbits with anesthesia produced by the injection of seconal(30 mg/kg). Rabbits had the cystic duct ligated and the proximal end of the divided common duct cannulated with an appropriately sized polyethylene catheter. A similar catheter was placed into the inferior vena cava for administration of drugs. Bile was collected for determination of cyclic nucleotides and total cholate in 15 min. intervals for a few hours. The results are summerized as followings. 1) Administrations of taurocholic acid or chenodeoxycholic acid increased significantly the concentrations of cAMP and cGMP in bile of rabbits. 2) Concentration of cAMP in bile during the continuous infusion of ursodeoxycholic acid, was remarkedly increased in accordance with the increase of bile flow, while on the contrary concentration of cGMP in bile was decreased significantly. 3) Dehydrocholic acid and deoxycholic acid significantly increased bile flow, total cholate output and cyclic nucleotides in bile. 4) Only cAMP concentration in bile was significantly increased from control value by secretin, while theophylline increased cAMP as well as cGMP in rabbit bile. 5) In addition, the administration of secretin to taurocholic acid-stimulated bile flow increased cAMP while theophylline produced the increases of cAMP and cGMP in bile. 6) The administration of insulin to taurocholic acid-stimulated bile flow decreased cAMP concentration, while on the contrary cGMP was remarkedly increased in rabbit bile.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.140-146
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• 2018

Though bile acids have been well known as digestive juice, recent studies have demonstrated that bile acids bind to their endogenous receptors, including Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1; TGR5) and serve as hormone to control various biological processes, including cholesterol/bile acid metabolism, glucose/lipid metabolism, immune responses, and energy metabolism. Deficiency of those bile acid receptors has been reported to induce diverse metabolic syndromes such as obesity, hyperlipidemia, hyperglycemia, and insulin resistance. As consistent, numerous studies have reported alteration of bile acid signaling pathways in type II diabetes patients. Interestingly, bile acids have shown to activate TGR5 in intestinal L cells and enhance secretion of glucagon-like peptide 1 (GLP-1) to potentiate insulin secretion in response to glucose. Moreover, FXR has been shown to crosstalk with TGR5 to control GLP-1 secretion. Altogether, bile acid receptors, FXR and TGR5 are potent therapeutic targets for the treatment of metabolic diseases, including type II diabetes.

• Korean Journal of Veterinary Research
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• v.37 no.4
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• pp.745-754
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• 1997

This study was designed to investigate the effects of cholate and deoxycholate on pancreatic exocrine secretion in conscious sheep with external bile and pancreatic fistulae. Bile and pancreatic juices were collected for a basal period of 2 hours. The pancreatic juice was returned to the intestine. Bile salts were infused into the jugular vein or duodenum for 90 minutes at the rate of 0.7mg/kg/min. Cholate and deoxycholate significantly increased the flow rate, pH and bicarbonate concentration of bile juice, but decreased the flow rate of pancreatic juice. The effects induced by intraduodenal infusion of both bile salts were significantly greater than those by intravenous infusion. Protein concentration and amylase activity in pancreatic juice were also significantly decreased by both bile salts; the effects were greater when the bile salts were infused into the duodenum than into the vein. The inhibitory effects induced by deoxycholate infusion were significantly greater than those by cholate infusion. The plasma concentration of secretin was significantly increased by intravenous infusion of deoxycholate, but it was not effected by intraduodenal infusion of both bile salts. The results indicated that cholate and deoxycholate markedly increased the secretion of bile juice and decreased the pancreatic exocrine secretion, although these effects were variable depending on the chemical composition or infusion routes.

• YAKHAK HOEJI
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• v.16 no.4
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• pp.176-179
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• 1972

The bile secretion was accelerated generally by the administration of all derivatives tested: chemodeoxycholate, deoxycholate, cholate, dehydrocholate, 7-ketochenodeoxycholate, and 3, 7-diketochenodeoxycholate in decreasing order. Bile acids content in bile from animals administered with cholate was increased, however, other derivatives did not alter the contents of bile acids and bilirubin. In view of pharmacological point, all derivatives have hydrocholeretic action, however, only cholate exhibits typical choleretic action.

• Korean Journal of Pharmacognosy
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• v.24 no.3
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• pp.258-262
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• 1993

The plant of Pedicularis resupinata var. oppositifolia(Scrophulariaceae) is described to be used for treatment of rheumatoid arthritis, malignant abscess (tumor), urolith and diuretics in oriental medicinal books. This study is concerned with some general pharmacological activities. It was observed that the methanol extract of the aerial part of this plant showed some effects on acute toxicity, carrageenin induced edema in rat paw, bile juice secretion and antibacterial effect. From this result it was obtained that the methanol extract revealed the antiinflammatory activity and bile juice secretion increasing effect. Thus, it was fractionated and buthanol fraction has obvious inhibition effect on edema and bile juice secretion increasing effect. The total extract showed low acute toxicity i.e., the minimum lethal dose was more than 8000mg/kg in oral administration in mice.

• Preventive Nutrition and Food Science
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• v.16 no.2
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• pp.104-109
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• 2011

Recently, we have demonstrated that green tea extract (GTE) decreases the intestinal absorption of benzo[a]pyrene (BAP), which is an extremely lipophilic food contaminant. The present study was conducted to examine if an enteral infusion of GTE would influence the biliary secretion of BAP and lipids in rats. Female rats were fed an AIN-93G diet with or without (control) GTE at 5 g/kg diet for 4 week. Following the 4-week dietary treatment, rats with bile duct cannula were infused continuously for 8 hr at 3.0 mL/hr via a duodenal catheter with a lipid emulsion containing $4.0\;{\mu}mol$ BAP labeled with $^{14}C$ ($^{14}C$-BAP), $20.7\;{\mu}mol$ cholesterol, $452\;{\mu}mol$ triolein, and $3.1\;{\mu}mol$ ${\alpha}$-tocopherol, and $396.0\;{\mu}mol$ Na-taurocholate with or without 76.1 mg GTE powder in PBS buffer (pH, 6.4). Bile was collected hourly via bile cannula for an 8 hr period. Our results showed that bile flow did not differ between groups. However, the biliary secretion of $^{14}C$-BAP was significantly enhanced by GTE infusion, compared with those infused with the lipid emulsion alone. However, GTE did not affect the biliary outputs of cholesterol, fat, phospholipid and ${\alpha}$-tocopherol. These findings indicate that GTE has a profound stimulatory effect on the biliary excretion of BAP in rats, without affecting other biliary lipids. The mechanism(s) by which GTE enhances the biliary secretion of BAP remains to be investigated.

• YAKHAK HOEJI
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• v.22 no.4
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• pp.193-200
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• 1978

Cholic, ursodesoxycholic, chenodesoxycholic, desoxycholic and hydesoxycholic acids were dissolved in the propylene glycol to make solution and then above solution of cholanic acids on bile secretion was investigated by injection those solutions into small intestine of rabbits and albino rats. The cholates in bile juice from rabbits injected with cholic acid were remarkably increased and therefore it exhibited a typical choleretic action. In view of pharmacological point, desoxycholic acid is considered as superior hydrocholeretic agent, and ursodesoxycholic and chenodesoxycholic acids have similar effect in decreasing order. However, the effect of bile secretion by hyodesoxycholic acid was almost negligible as that by propylene glycol administered. The cholate content in the bile juice from albino rat was increased by cholic and desoxycholic acids in decreasing order: i.e., they exhibited choleretic action. In the case of ursodesoxycholic and chenodesoxycholic acids, the concentration of cholate was slightly increased in bile juice from the rat, so that these cholates showed a weak choleretic action. While total output of bilirubin was increased by chenodesoxycholic acid, the other cholanic acid showed no effect in the rabbit.

• Korean Journal of Pharmacognosy
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• v.17 no.4
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• pp.292-301
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• 1986

The combined preparations of the traditional Korean prescriptions, Sahyangsohap-won (A1) and Woohwangporyong-hwan (B1) were evaluated on pharmacological actions in rats and mice, in parallel with the preparations of their modified prescriptions (A2 and B2). The acute toxicities of the four preparations were very low of which $LD_{50}$ values were more than 4g/kg, p.o. and no systematic symptoms were found at the doses. All the preparations showed sedative action by prolongation of sleeping time induced with hexobarbital sodium. The action was more potent in the modified preparations than in the original ones. All the preparations had no anticonvulsant action both in chemoshock seizures induced by pentetrazole and strychnine and in electroshock seizure. In rat fundus preparation, A1 and A2 elicited strong contraction at the concentration of $1{\times}10^{-3}\;g/ml$ in bath, whereas B1 and B2 did neither contraction nor relaxation at the same concentration. The four preparations had no inhibitory effect against acetylcholine induced spasm. In rat intestinal preparation, the four preparations exhibited neither contraction nor relaxation. However, A1 and A2 had antagonistic effect against spasm at the concentration of $1{\times}10^{-3}\;g/ml$. Single administration of each preparation at the dose of 0.24g/kg, p.o. stimulated the secretion of pepsin in rat stomach without inciting the secretion of gastric juice. Their stimulating actions were more marked in B1 and B2 than in A1 and A2, and were more promptly exhibited in the modified preparations (A2 and B2). Accelerating action of bile secretion by single administration of each preparation was found at the dose of 0.24g/kg, p.o. in rats. All the preparations except A2 also stimulated the secretion of bile acid.

• Applied Microscopy
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• v.20 no.1
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• pp.51-64
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• 1990

This experiment was performed to study the morphological changes of the goblet cells in the rabbit duodenal mucosa after common bile duct ligation. Healthy adult rabbits weighting about 2kg body weight were divided to normal and bile duct ligated groups. Common bile duct ligation was performed under ether anesthesia. Experimental animals were sacrificed on the 1st, 3rd, 5th, 7th and 14th day after the operation. Mucosal specimens from the upper part of duodenum were fixed in 2.5% glutaraldehyde-1.5% paraformaldehyde, followed by 1% osmium tetroxide, embedded in araldite mixture, cut with LKB-V ultratome, stained with uranyl acetate - lead citrate, and observed with JEM 100 CX II electron microscope. Observed results were as follow : 1. In the early stages(1st-5th day) of the experiments, the goblet cells showed apocrine and merocrine secretion. But those of the late stage(7th and 14th day) groups showed exocytotic merocrine secretion. 2. In the late stage of the experiments, there found than increase of newly formed goblet cells that contain electron lucent cytoplasms. 3. In the goblet cells of normal rabbit, mucous granules with higher or lower electron densities are found together in the cytoplasm, and electron lucent mucous granules occasionally fused together. But in the early stage of the common bile duct ligation, goblet cells contained granules of higher electron densities. 4. Considering the above findings, common bile duct ligation probably initiates the hypersecretion of mucous granules of goblet cells in the early stage, and may facilitate the differentiation of goblet cells in the later stage.