Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors describe the association of gold salt-induced cholestasis and lymphocytic alveolitis proved by liver biopsy and broncho-alveolar lavage. To our knowledge this is the third case report on the combination of liver disease and pulmonary infiltration induced by gold compounds.
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PMID:Cholestasis and pneumonitis induced by gold therapy. 261 24

S-Adenosyl-L-methionine (SAMe) is a naturally occurring molecule distributed to virtually all body tissues and fluids. It is of fundamental importance in a number of biochemical reactions involving enzymatic transmethylation, contributing to the synthesis, activation and/or metabolism of such compounds as hormones, neurotransmitters, nucleic acids, proteins, phospholipids and certain drugs. The administration of a stable salt of SAMe, either orally or parenterally, has been shown to restore normal hepatic function in the presence of various chronic liver diseases (including alcoholic and non-alcoholic cirrhosis, oestrogen-induced and other forms of cholestasis), to prevent or reverse hepatotoxicity due to several drugs and chemicals such as alcohol, paracetamol (acetaminophen), steroids and lead, and to have antidepressant properties. In all of these studies SAMe has been very well tolerated, a finding of great potential benefit given the well-known adverse effects of tricyclic antidepressants with which it has been compared in a few trials. Thus, with its novel mechanisms of action and good tolerability, SAMe is an interesting new therapeutic agent in several diverse disease conditions, but its relative value remains to be determined in appropriate comparisons with other treatment modalities in current use.
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PMID:S-adenosyl-L-methionine. A review of its pharmacological properties and therapeutic potential in liver dysfunction and affective disorders in relation to its physiological role in cell metabolism. 268 Apr 35

To determine whether in complete obstructive cholestasis taurocholate is taken up by hepatocytes and if so whether it is secreted into bile, tritium-labelled taurocholate was localized by histoautoradiography on cryoslices from normal rat livers and from those after bile duct ligation. In non-cholestatic livers the hepatocytes of acinar zones 1 as well as the lumina and the epithelia of bile ductules and ducts became intensely labelled directly after injection of [3H]taurocholate into a mesenterial vein. Four hours and 4 days after bile duct ligation, hepatocytes of all three acinar zones became labelled, but in contrast to the normal state, pericanalicular concentration of silver grains was not observed, not even within 5 min. Fifteen days after bile duct obstruction, cryoslices taken 2 min after injection of [3H]taurocholate exhibited an intense silver grain labelling of all acinar zones, with the highest density at bile canalicular areas of the liver cell plates as well as the proliferated bile ductules and bile ducts. The biliary epithelium of small bile ductules and ducts of non-cholestatic and of bile duct-obstructed livers were also covered with silver grains; the epithelium of larger ducts exhibited significant labelling predominantly at the lateral sites of the cells. The biliary epithelium of the common bile duct was not significantly labelled. The results indicate that in complete obstructive cholestasis (a) taurocholate continues to be taken up from blood by hepatocytes and secreted into bile, but in terms of varying duration of obstruction, (b) all acinar zones are involved in bile salt transport, (c) in the initial phase (4 h and 4 days respectively after bile duct obstruction) hepatocytes fail to concentrate taurocholate at the canalicular site, (d) in a consecutive phase, in which bile ductules and ducts proliferate (demonstrated for a 15-day cholestasis), the taurocholate concentration at the canalicular site of hepatocytes is re-established and biliary secretion seems to be enhanced, (e) the biliary epithelium of bile ductules and ducts may play a significant role in the reabsorption and/or regurgitation of bile salts from bile to blood. Reabsorption/regurgitation of biliary constituents may also be operative in the non-cholestatic state but may become significantly enhanced with bile ductular proliferation.
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PMID:The histoautoradiographic localization of taurocholate in rat liver after bile duct ligation. Evidence for ongoing secretion and reabsorption processes. 271 21

To elucidate the consequences of extrahepatic cholestasis on the structure and function of hepatocytes, we studied the effects of bile duct ligation on the turnover, surface distribution, and functional activity of the canalicular 100-kD bile salt transport protein (cBSTP). Basolateral (blLPM) and canalicular (cLPM) liver plasma membrane vesicles were purified to the same degree from normal and cholestatic rat livers and the membrane bound cBSTP identified and quantitated using polyclonal anti-cBSTP antibodies. Cholestasis of 50 h resulted in an increased release of cBSTP into bile, thereby decreasing its in vivo half-life from 65 to 25 h. Furthermore, a significant portion of cBSTP accumulated at the basolateral surface and in intracellular vesicles of cholestatic hepatocytes. This redistribution of cBSTP was functionally paralleled by decreased and increased electrogenic taurocholate anion transport in cLPM and blLPM vesicles, respectively. These results demonstrate that biliary obstruction causes a reversal of the bile salt secretory polarity of rat hepatocytes. The resulting increase in basolateral (sinusoidal) bile salt efflux might protect hepatocytes from too high an accumulation of toxic bile salts within the cell interior.
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PMID:Extrahepatic obstructive cholestasis reverses the bile salt secretory polarity of rat hepatocytes. 276 Feb 17

The bile to plasma 125I-albumin concentration ratio (B/P ratio) was examined before and during various bile salt infusions in male Wistar rats that had previously received iv injection of 125I-albumin. Endogenous rat albumin and IgG concentrations in the bile were also determined by a single radial immunodiffusion method. Taurocholate (TC) infusion (1.0 mumol/min/100 g body wt) significantly increased the bile flow rate in the first hr but the flow began to decline in the second hr. The B/P ratio as well as rat albumin (and IgG) excretion into the bile significantly increased as early as 15 min after the start of TC infusion, and the increase became more pronounced in the second hr, when the bile flow began to decrease. Infusion of taurochenodeoxycholate (TCDC, 0.4 mumol/min/100 g) caused a reduction in bile flow 15 min after the start of infusion but the B/P ratio increased 40 times at its peak compared with the basal value before the bile salt infusion. Simultaneous infusion of tauroursodeoxycholate (TUDC, 0.6 mumol/min/100 g) and TCDC not only abolished the cholestasis induced by TCDC but maintained stable choleresis as long as for 2 hr. During this choleretic period, the B/P ration never exceeded the basal value. The choleresis induced by either taurodehydrocholate (TDHC) or bucolome was not accompanied by enhanced albumin excretion. In rats given TDHC infusion, albumin excretion started to increase only after the bile flow began to decline following the initial choleretic period. The enhanced excretion of albumin induced by TC and TCDC is therefore suggested to be caused not by the choleresis per se but by a possible concomitant increase in the communication between sinusoids and bile canaliculi, which eventually leads to cholestasis. Our results suggest that the biliary excretion of albumin enhanced by bile salt infusion in rats is primarily the result of hepatocyte damage closely related to cholestasis rather than to choleresis, and that the rate of such excretion can be used as a convenient and reliable marker for hepatocyte damage.
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PMID:Biliary albumin excretion induced by bile salts in rats is a pathological phenomenon. 281 58

Certain bile salts cause hepatotoxicity as well as injury to extrahepatic organs when administered to animals. Activated neutrophils (PMNs) may cause tissue injury by releasing reactive oxygen species and other products. Since PMNs may come in contact with biliary components, such as bile salts, following chemical insult to the liver or during cholestasis, we examined the capacity of bile and bile salts to stimulate superoxide anion (O2-) release from rat peritoneal PMNs in vitro. Neither bile nor bile salts, with the exception of lithocholate, could by themselves stimulate O2- release from PMNs. Lithocholate (32 microM) caused small but statistically significant release of O2- from PMNs. When PMNs were primed with a barely suprathreshold concentration of 12-O-tetradecanoyl-phorbol-13-acetate (PMA), a classic stimulus for PMNs, the addition of bile and certain bile salts markedly enhanced O2- release from PMNs. The monohydroxy bile salt, lithocholate, had the greatest stimulatory activity toward PMA-primed PMNs, causing approximately an eightfold increase in O2- release. The enhancing effect of lithocholate was maximal between 10 and 32 microM, and it also occurred with PMNs isolated from rat blood. Dihydroxy bile salts, deoxycholate and chenodeoxycholate (100 microM), caused more modest enhancement of O2- release (two- to threefold) from primed PMNs. Cholate, a trihydroxy bile salt, was not active at these concentrations. Conjugation of either lithocholate or chenodeoxycholate with either glycine or taurine markedly reduced the ability of the bile salt to enhance O2- release from primed PMNs. Structural alterations on the hydrophilic side chain or within the planar, hydrophobic portion of the bile salt molecule reduced the capacity to enhance O2- release from PMA-primed PMNs. These results indicate that bile salts can potentiate the respiratory burst in PMNs and suggest a role for this interaction in toxicoses or disease states characterized by elevated serum bile salts.
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PMID:Bile and bile salts potentiate superoxide anion release from activated, rat peritoneal neutrophils. 284 92

Previous experiments have demonstrated the cholestatic effects of somatostatin administration in several animal species. These effects were confirmed in the rat. Nine pairs of intact awake rats received intravenous sodium taurocholate (23 mg hr-1) to stabilize bile flow, and half were later given somatostatin at doses of 185 micrograms hr-1. After 1 hr of somatostatin the experimental group showed a significant decrease in bile flow compared to the control group. Cholestasis reversed when somatostatin infusion was stopped. An in situ isolated perfused rat liver technique was used to assess the direct effects of somatostatin on biliary flow. In 10 pairs of rat livers, after achieving stable bile flow, half of those perfused (the "experimentals") received continuous (370 micrograms hr-1) somatostatin infusion, while the controls received saline. The percentage change in bile flow from baseline in the somatostatin group was not significantly different from that in controls for any test period. Bile analysis revealed no significant differences between groups for cholesterol, phospholipid, or bile salt concentrations or outputs. These data suggest that somatostatin inhibits bile secretion by some mechanism other than direct inhibition of bile secretory mechanisms.
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PMID:Is somatostatin a directly acting cholestatic hormone? 286 22

Gallbladder 'sludge' and cholestasis are two common complications associated with total parenteral nutrition (TPN), but the aetiology of each is uncertain. An animal model has been developed in the young pig which demonstrates these two complications. Five female piglets, of Landrace Large White Cross variety weighing 4.5-5.9 kg, received nutritional support for 2 weeks with a continuous infusion of TPN solution at a dose of 150 kcal kg-1 day-1. The solution was 35 per cent dextrose, 5 per cent L-amino acids with conventional electrolyte, mineral and vitamin additives. No lipid was used in the solution. Five weight-matched animals were used as controls. All animals in the TPN group developed 'sludge' in their gallbladders, decreased basal bile flow, decreased bile salt excretion and a diminished response to bile salt stimulated bile flow, as compared with controls. There was no abnormality in routine liver function tests or liver histology. It is concluded that TPN therapy in this animal model is associated with the appearance of gallbladder 'sludge', and cholestasis as demonstrated by direct bile flow studies. It is suggested that this bile flow abnormality is due to a decrease in bile salt dependent and bile salt independent fractions of canalicular bile flow. The model provides the opportunity to investigate TPN related hepatobiliary dysfunction in an animal that has similar liver function to man and comparable nutritional requirements.
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PMID:Model of TPN-associated hepatobiliary dysfunction in the young pig. 311 27

Biliary secretory pressure represents the force generated to deliver bile through the biliary system. Bile acid-induced toxicity may decrease canalicular bile formation and (or) induce back diffusion causing cholestasis. To determine if biliary secretory pressure is a sensitive indicator of bile toxicity, taurocholate was compared with a less cytotoxic bile acid, tauroursodeoxycholate. In fasted male Sprague-Dawley rats, the common bile duct was cannulated and the endogenous bile salt pool was removed by enteroclysis. Taurocholate (n = 35) or tauroursodeoxycholate (n = 35) in saline was infused for 1 h. Maximal biliary secretory pressure was then measured by attaching the biliary cannula to a column monometer and recording the maximum height to which bile rose. With taurocholate administration, bile flow and bile salt secretion linearly rose to a maximum infusion of 0.5 mumol/(min.g liver), above which hemolysis and death occurred. In contrast, tauroursodeoxycholate could be infused at higher rates with bile salt secretion plateauing at 1.25 mumol/(min.g liver] Both had similar choleretic potencies. Mean biliary secretory pressure at low (less than 0.15 mumol/(min.g liver] infusions was lower with taurocholate (22.5 cm bile) than tauroursodeoxycholate (25.2 cm). Further, increasing the taurocholate infusion decreased the biliary secretory pressure; yet for taurousodeoxycholate, pressure remained unchanged even at higher infusions. Thus, taurocholate but not tauroursodeoxycholate decreases biliary secretory pressure at high infusion rates, likely a reflection of its toxicity to the hepatobiliary epithelium.
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PMID:Determinants of biliary secretory pressure: the effects of two different bile acids. 324 Apr 13

Cyclosporin A is known to be eliminated mainly via the biliary++ pathway after biotransformation. Whether liver cells take up the drug by simple diffusion across the lipid barrier or by carrier-mediated transport, as shown for some other peptides, was unknown up to the present. Experiments with [3H]cyclosporin A on isolated rat hepatocytes indicate that the uptake of cyclosporin A is neither saturable nor is driven by metabolic energy. Cholestasis caused by cyclosporin A treatment is therefore not the result of mutual competition for a carrier protein. Nevertheless, cyclosporin A interacts with the bile acid transport system by non-competitive inhibition of bile salt uptake.
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PMID:Hepatocellular uptake of cyclosporin A by simple diffusion. 333 16


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