Bile In High Concentrations Research Articles

High concentration bile combined with infection induces pro-inflammatory reaction through activation of the inflammasome in monocytes

Objective To investigate the signal pathway of high concentration bile triggering monocyte proinflammatory response.Methods The peripheral blood monouclear cells (PBMCs) of rats were isolated and cultured in vitro.The concentration of 5％ bile in rats was prepared.The PBMCs were cocultured with 5％ bile,endotoxin (LPS),adenosine-triphosphate (ATP),or high K+ culture fluid.The cytotoxicity was detected by lactate dehydrogenase (LDH) after 1,6,12,and 24 h.The contents of interleukin (IL)-1β were determined by using enzyme linked immunosorbent assay (ELIAS),and the expression of Caspase-1 and NALP3 was detected by using Western blotting and analyzed quantitatively.Results 5％ bile only was failed to induce expression of interleukin (IL)-1β,Caspase-1 or NALP3.But the levels of IL-1β were increased to (769.8 ± 29.4) and (788.6 ± 32.4) ng/L after pretreatment with LPS or ATP,which were significantly higher than single LPS group [(88.1 ±6.7) ng/L,P ＜0.01].The levels of IL-1β reached the peak [(871.1 ± 69.7) ng/L] at 6th h after pretreatment with LPS.There was no correlation between LDH and IL-1β.Western blotting analysis demonstrated that the Caspase-1 protein generated a band about 1.0 × 104 and a broad band about 1.2 × 105 of NALP3 in LPS + bile group.The quantitative analysis showed that the expression of Caspase-1 and NALP3 was higher obviously in LPS + bile group than that in single LPS group.Concentration of IL-1β was decreased in LPS + bile group after culture with high K+ substratum for 6 h.Conclusion The high concentration of bile in the blood circulation combined with bacterial infection induces proinflammatory responses via activation of the NLRP3 inflammasome.The potassium efflux is required for the procedure. Key words: Bile; Inflammatory; Interleukin-1β; Inflammasome

High concentration bile changes the chloride channel protein-2 and permeability of intestinal epithelium cell line

Objective To investigate the effects of bile on chloride channel protein-2 (CLC-2)and permeability of intestinal epithelium cell.Methods Rat intestinal epithelium cell line IEC-6 was cultured.They were exposed to 5.0％,1.0％,0.1％ rat bile and chloride channel agonist Lubiprostone.After 20 h cultured,transepithelial electrical resistance (TER) of the monostratal cells was measured.The change of CLC-2 and zonula occludens-1 (ZO-1) were examined by Western blotting,and the images were analysed quantitatively.Results The TEER of 5％ group was most lower.The average relative gradations of Western blotting images in 5.0％ group and 1.0％ were lower obviously than those in control group (0.30 ± 0.05,0.37 ± 0.08 vs.0.56 ± 0.08) ( all P ＜ 0.05 ).The relative gradations of ZO-1 were decreaseded only in 5.0％ group.After Lubiprostone added,the TER in 5.0％ group was upgraded (451.3 ± 60.5 )Ω·cm2,and the average relative gradations of ZO-1 (0.32 ± 0.04).Conclusion High concentration of bile destroied enterocyte chloride channel and tight junction protein,increase epithelium permeabihty. Key words: Bile; Enterocyte; Chloride channel protein-2 ; Permeabihty

Urinary, biliary and faecal excretion of rocuronium in humans

The excretion of rocuronium and its potential metabolites was studied in 38 anaesthetized patients, ASA I-III and 21-69 yr old. Rocuronium bromide was administered as an i.v. bolus dose of 0.3 or 0.9 mg kg-1. In Part A of the study, the excretion into urine and bile, and the liver content were studied. Plasma kinetics (n = 19) were similar to those reported previously. Urinary recovery within 48 h after administration was 26 (8)% (mean (SD)) (n = 8) of the dose. In bile obtained from T-drains, the recovery within 48 h was 7 (6)% (n = 11). The rocuronium concentration in bile declined bi-exponentially, with half-lives of 2.3 (0.7) and 16 (11) h respectively (n = 6). In three patients from whom stoma fluid was collected, the amount of rocuronium recovered ranged from 0.04 to 12.0% of the dose. In liver tissue obtained from four patients undergoing hemihepatectomy, the estimated amount of rocuronium at 2-5 h after administration ranged between 6.3 and 13.2% (n = 4). In the second part of the study (Part B), urine and faeces were collected over 4-8 days and the recovery was 27 (13)% and 31 (23)% of the dose respectively (n = 10). In most samples, irrespective of the type of biological material, only small amounts of the metabolite 17-desacetyl-rocuronium was found. The results demonstrate that rocuronium is taken up by the liver and excreted into bile in high concentrations. The faecal and urinary excretion of unchanged rocuronium are the major routes of rocuronium elimination.

Studies on the biliary excretion mechanisms of drugs. 3. Active transport of glucuronides into bile in rats.

Thiamphenicol glucuronide (TPG), chloramphenicol glucuronide (CPG) and phenolphthalein glucuronide (PPG), administered intravenously to rats with ligated renal pedicles, rapidly appear in the bile in high concentrations as the unchanged compounds. Between 4 and 30 min after administration, the bile-to-blood concentration ratios of the glucuronides are 33-122 for TPG, 35-142 for CPG and 6-101 for PPG. Furthermore, the transport process of the glucuronides is saturable and the excretion is depressed by probenecid. The results indicate that TPG, CPG and PPG are excreted into the rat bile by an active transport process.

Active transport of quaternary ammonium compounds into bile.

The quaternary ammonium ion, procaine amide ethobromide (PAEB), administered intravenously (5 mg/kg) to rats with ligated renal pedicles, rapidly appears in the bile in high concentrations, both as free PAEB and as conjugated PAEB. During 1 hr after administration of the compound, the biliary concentrations of free as well as conjugated compound are about 80 times greater than the plasma concentrations. Raising the dose of PAEB does not result in an increased excretion of the compound, indicating that the excretion process is saturable. A number of quaternary amine compounds markedly depress the excretion of PAEB while others do not, suggesting a competition for transport and a certain degree of specificity for the transport process. The results indicate that the liver has an active secretory process for the transport of certain quaternary ammonium ions from blood to bile. The process appears to be different from that which actively secretes organic anions such as Bromsulphalein, bile acids, and fluorescein, since high doses of Bromsulphalein and sodium glycocholate do not inhibit the transport of PAEB.