• Journal of Pharmaceutical Investigation
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• v.7 no.1_4
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• pp.38-50
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• 1977

A study on the mechanism of biliary and urinary excretion of chloramphenicol has been performed in the dog. 1) Chloramphenicol administered intravenously to dogs with ligated renal pedicle, readily appeared in bile greater than in plasma. 6.9% of a 50mg /kg i. v. dose of chloramphenicol were excreted into bile within 100 minutes. During the same periods of above experiment, the bile/plasma concentration ratios(B/P ratios) were 46 to 87. 2) Chloramphenicol injected into the vein of dog was rapidly excreted into urine. 18% of the administered dose were excreted into urine within 70 minutes. In the same periods of this experiment, Ccm/Ccr ratios were greater than 1.0 in most cases. 3) In experiment of simultaneous measurement of biliary and urinary excretion of chloramphenicol, Ccm/Ccr ratios were less than 1.0 and B/P ratios were 50 to 52. 4) In experiment measured simultaneously biliary and urinary excretion both Ccm/Ccr and $C^Hcm$(hepatic clearance) were significantly declined by probenecid, but not affected by 2,4-DNP and aminophylline although 2,4-DNP increased only bile flow and aminophylline both bile and urine volume. 5) Ccm/Ccr and $C^Hcm$ were increased in proportion to increment of plasma concentration ranging from 3.3 to 30 mg% of chloramphenicol. But when plasma concentration were increased to 70mg %, Ccm/Ccr were not increased and $C_Hcm$ were reduced about 30% in comparison with values obtajned at 30mg% of chloramphenicol. 6) Free/Bound(free to bouid from) ratios ranging from 1.0 to 90.0mg% of chloramphenicol were 76.2+3.72% $(mean{\pm}S.E.)$ Above results suggest that chloramphenicol is excreted into bile by a process of active trasport, that excretion of chloramphenicol into urine was made up with dual process, reabsorption and secretion, and that renal secretion was attained by active trasport process although renal reabsorption process could not understand.

• Korean Journal of Veterinary Research
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• v.35 no.3
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• pp.481-488
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• 1995

In oriental folk medicine, Artemisia messes-schmidiana var viridis(Compositae) has been used for jaundice, hepatitis, diuretic and liver cirrhosis etc. 1-naphthylisothiocyanate(ANIT) has been used for more than 20 years as a model compound to study mechanisms of intrahepatic cholestasis in laboratory animals as rat and mouse. Various biochemical and morphological changes including biliary epithelial and parenchymal cell necrosis occur in the liver of animals treated with ANIT. The purposes of present study are to examine pharmacological effects of Artemisia messes-schmidiana var viridis water extract(AMWE) on alterations of secretion volume and total bile acids level in bile juice, and that of serum AST, ALT, ALP, bilirubin, and glucose levels in rat. AMWE stimulated bile secretion and recovered ANIT-induced cholestasis. Bile acid concentrations increased to more than 60% compared with normal by ANIT, which were returned toward normal value with AMWE treatment. Serum AST and ALT activities were increased by ANIT and yet which were significantly decreased with AMWE treatment. In addition, this effect was apparent in AMWE pretreatment group. Serum glucose levels were increased with AMWE and ANIT, while were decreased compared with control in AMWE posttreatment group. Increased serum total bilirubin contents and ALP activities by ANIT were significantly decreased with AMWE posttreatment. In conclusion, AMWE exerted bile acid-independent choleresis effect and then improved to normal conditions ANIT-induced cholestatic syndromes. Also, AMWE have protective and regenerative effect of hepatocytes in rat.

• Applied Microscopy
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• v.29 no.4
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• pp.437-450
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• 1999

Bile canaliculi are the structure delivering bile secreted by hepatocytes into the bile passage. Bile secretion is mainly controlled by the cytoskeletal elements, mainly of actin in the microvilli, pericanalicular web. Most studies on the bile secretion have been done in viva situation, however, to control the various parameters in vitro culture system seem to be more useful. To set up an in vitro experimental system, the investigator isolated hepatocytes with an enzymatic method using a mixture of collagenase and hyaluronidase from normal Sprague-Dawley rat liver and cultured. Isolated hepatocytes were round and formed cords in culture. Microvilli covered the whole surface of hepatocytes. Bile canaliculi were formed between hepatocytes and were characterized by the presence of microvilli of various lengths and shapes mainly arising from small surface mounds. Actin filament core in the microvilli and pericanalicular actin web were incomplete. After cytochalasin D treatment, cultured hepatocytes were round but the surface were irregular with surfacen blebs, folds and grooves. Microvilli on the surface were scarce. Bile canaliculi were markedly dilated often with the detached junctional complexes. Bile canaliculi lacks microvilli almost completely and extended into the pericanalirular cytoplasm showing complex vacuolar and tubular structures by transmission electron mciroscopy. Pericanalicular actin web, intermediate filaments were hardly identified. Subsurface actin filaments were scattered scarcely under the cell membranes. These results suggest that hepatocytes isolated from rats can survive and form bile canaliculi in culture and the actin filaments are involved in the formation and/or maintenance of the bile canaliculi.

• Journal of the Korean Chemical Society
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• v.42 no.3
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• pp.266-276
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• 1998

Cholesterol supersaturation in bile, which causes gallstone formation, is the result of low bile acid secretion or high cholesterol secretion. The quantitative analysis of cholesterol, bile acids and sterols which are precursors of cholesterol have been used to examine the changes in bile component. We described a simple, sensitive and reproducible method for simultaneous determination of cholesterol, five bile acids and seven sterols in human bile juices and gallstones by capillary column gas chromatography-mass spectrometry (GC/MS). Clinical samples were hydrolyzed by alcoholic KOH, extracted twice (pH 14 and 1) and derivatized to trimethylsilyl (TMS) ether with $MSTFA/NH_4I$ (N-methyl-N-trimethylsilyltrifluoroacetamide/ammonium iodide) mixture in order to be detected on the GC/MS. The good quality control data were obtained through within-a-day and day-to-day test (RSD values were 1.72-13.79, 0.68-14.10, respectively) and the recovery range of them was 73.56-96. 95 Using this method, biliary and gallstone compositions in the patients with intrahepatic stones were analyzed. The amounts and its relative distribution of cholesterol, bile acids and sterols showed different pattern in bile juices and gallstones.

• YAKHAK HOEJI
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• v.46 no.3
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• pp.192-196
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• 2002

To investigate the effect of intravenous ethanol administration on pancreatic exocrine secretion, we measured volume and protein amount in pancreatic juice and assayed amylase activity and phospholipase $A_2$ activity in pancreatic fragments and serum. Acute pancreatitis induced by obstruction of common bile-pancreatic duct (CBPD) and caerulein infusion (5 $\mu\textrm{g}$/kg/hr) showed typical characteristics, such as hyperamylasemia and pancreatic edema and increase of phospholipase $A_2$ activity in pancreatic fragments and serum. Intravenous ethanol infusion (50 mg/kg/hr) significantly stimulated pancreatic exocrine secretion, but such a stimulatory effect of ethanol disappeared at dose of 100 mg/kg/hr without typical symptoms of acute pancreatitis. In microscopic examination, there were no typical changes of edematous pancreatitis in ethanol administrated rats. These results suggest that acute ethanol administration has dual effect on exocrine pancreatic secretion: low dose of ethanol (50 mg/kg/hr) stimulates pancreatic exocrine secretion, whereas high dose of ethanol (100 mg/kg/hr) does not without typical changes of edematous pancreatitis.

• Korean Journal of Pharmacognosy
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• v.27 no.1
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• pp.47-52
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• 1996

A triterpenoid(melianone) and a limonoid(28-deacetyl sendanin) were isolated from the chloroform fraction of Meliae toosendan Fructus, the rippen fruits of Melia toosendan SIEB. et ZUCC.(Meliaceae) and were applied to serial experiments to clarify the liver protective activities. We found that the compounds promoted slightly the drug metabolizing enzyme activities and decreased serum transaminase activities which was elevated by carbon tetrachloride intoxication. And also they slightly increased the secretion of bile juice in rat.

• Korean Journal of Pharmacognosy
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• v.24 no.1
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• pp.63-68
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• 1993

Meliae toosendan Fructus is the fruit of Melia toosendan $S_{IEB}$. et $Z_{UCC}$. (Meliaceae), which is written in oriental terminology as clearing heat and drying dampness, and also explained using liver, stomach and small intestine for channels entered. Among the five fractions prepared from methanol whole extractive of the herb, the chloroform fraction which suggests the presence of triterpenoid, flavonoid and alkaloid stimulated the activities of drug metabolizing enzymes and bile secretion and lowered the serum transaminase activities of liver damaged by carbon tetrachloride.

• The Korean Journal of Pharmacology
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• v.12 no.1
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• pp.15-22
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• 1976

The clinical abuse of C.N.S. stimulants during recent years has directed particular attention. Effect of various organs other than C.N.S. was also extensively investigated with those agents. It has been shown that, although there is a wide variation in sensitivity between species, caffeine stimulates gastric secretion in man, cat, guinea pig and dog. Roth and Ivy(1944) reported that caffeine and histamine acted synergistically in stimulating gastric secretion in the cat. Vaille et al(1966) studied that production of pancreatic juice in the rat was enhanced, but bile secretion was not affected by caffeine. In clinical study the effect of chlorpromazine on the external pancreatic secretion in the 24 subjects, the volume fell more than 20% in 7 subjects. (Skajaa et al 1960) It is widely known that C.N.S. stimulants enhanced spontaneous motor activity in the mice, while tranquilizers depressed the activity. Woo (1975) reported that the group of mice treated with chlorpromazine showed markedly inhibited motor activity and in the group of mice treated with amphetamine, there was a significant increase in the motor activity. The purpose of the present experiment was to study the effects of C.N.S. stimulants and depressant on the exocrine pancreas, and on the spontaneous motor activity in the rats. The results obtained are summarized as follows. 1. In animals treated with xanthine derivatives, the volume of pancreatobiliary secretion was markedly increased. 2. Total bilirubin output was elevated markedly in the xanthine derivatives and imipramine treated animals. The bilirubin concentration was increased in xanthine derivatives treated group. 3. The concentration of cholate in the bile was decreased in the chlorpromazine treated group. 4. The activity of lipase in the pancreatobiliary juice was elevated markedly in the xanthine derivatives treated group only. 5. In the all experimental groups, the activity of amylase in pancreatobiliary juice was significantly elevated. 6. In the caffeine treated group, spontaneous motor activity was markedly increased in $30{\sim}60$ minutes, and the amphetamine treated group showed the increased motor activity in first 30 minutes. 7. The group of rats treated with chlorpromazine showed markedly inhibited motor activity after 30 minutes, and the imipramine treated group showed similar result but less inhibition.

• Nutrition Research and Practice
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• v.4 no.6
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• pp.462-469
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• 2010

Protamine has been widely used as a pharmaceutical product and natural food preservative. However, few studies have been conducted to assess the beneficial function of dietary protamine. This study examined the effects of dietary salmon protamine on serum and liver lipid levels and the expression levels of genes encoding proteins involved in lipid homeostasis in the liver of rats. Groups of male Wistar rats were fed AIN93G diet containing 2% or 5% protamine. After 4 weeks of feeding these diets, markedly decreased serum and liver cholesterol (CHOL) and triacylglycerol levels were noted. Increased activity of liver carnitine palmitoyltransferase-2 and acyl-CoA oxidase, which are key enzymes of fatty acid ${\beta}$-oxidation in the mitochondria and peroxisomes, was found in rats fed on protamine. Furthermore, rats fed protamine showed enhanced fecal excretion of CHOL and bile acid and increased liver mRNA expression levels of ATP-binding cassette (ABC) G5 and ABCG8, which form heterodimers and play a major role in the secretion of CHOL into bile. The decrease in triacylglycerol levels in protamine-fed rats was due to the enhancement of liver ${\beta}$-oxidation. Furthermore, rats fed protamine exhibited decreased CHOL levels through the suppression of CHOL and bile acid absorption and the enhancement of CHOL secretion into bile. These results suggest that dietary protamine has beneficial effects that may aid in the prevention of lifestyle-related diseases such as hyperlipidemia and atherosclerosis.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.74-74
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• 1997

Chicory is used popularly. We use leaves of the plant as ordinary mea1, and roots as a substitute of tea materials. It also has been asserted that it has clinical effects on weakness, hepatic disease, diabetes, etc. However, experimental evidences are so insufficient that we started these studies. For antiinflammatory activity, MeOH Ex. was orally administered to rats, and decreased amounts of paw edema induced by carrageenan injection were measured. For bile secretion increament, rats were administered total MeOH, EtOAc fraction, and BuOH fraction Ex. respectively. One hour later, bile ducts were cannulated, and we collected bile every 20 minutes for 4 hours. For hepatoprotective activity, CCl$_4$-intoxicated mouse were treated with MeOH Ex., then s-GPT, S-GOT, and liver weight were measured. For antidiabetic activity, rats were induced diabetes by streptozocin 45mg/kg(i.v) injection. One week later, 1000mg/kg of total MeOH Ex. of chicory root was orally administered. We divided rats into three groups. Group 1 rats were administered only once, group 2 ones once a day for one week, and group 3 ones for three weeks. The concentrations of serum glucose were measured before and after administration. For antihypertensive activity, SHR were administrated total MeOH Ex. of chicory once a day for 8 days, and were measured blood pressure on 1st, 3rd, 6th and 8th day. Total MeOH, EtOAc fraction, and BuOH fraction Ex. increased bile secretion in rats, and decreased liver toxicity induced by CCl$_4$ in mouse. Total MeOH, Ex. of chicory roots has antiinflammatory effect, and decreased blood glucose concentration in group 2 and 3 rats. It was revealed not lowering blood pressure significantly in SHR.