scholarly journals Differences between the biliary excretion of tri[14C]methyl-1-(3-hydroxyphenyl)ammonium iodide in Wistar and Gunn rats

1970 ◽  
Vol 119 (4) ◽  
pp. 659-663 ◽  
Author(s):  
T. N. Calvey ◽  
S. M. Somani ◽  
Antoinette Wright
Keyword(s):  
Biliary Excretion ◽  
Wistar Rats ◽  
Ammonium Iodide ◽  
Unchanged Drug ◽  
Canalicular Membrane ◽  
Gunn Rat ◽  
Gunn Rats ◽  
Biochemical Lesion ◽  
Rat Bile

1. The biliary excretion of [14C]trimophonium iodide [tri[14C]methyl(3-hydroxyphenyl)ammonium iodide] was studied in normal Wistar animals and in jaundiced homozygous Gunn rats. 2. In normal Wistar rats small amounts of radioactivity (approx. 3% of the dose in 4h) were excreted in bile as two glucuronide conjugates, i.e. [14C]trimophonium glucuronide [tri[14C]methyl-(3-oxyphenyl)ammonium glucuronide] (85%) and 3-di[14C]methylaminophenyl glucuronide (10–15%). Only minor amounts of the unchanged drug were detected in bile. 3. In the homozygous jaundiced Gunn rat large amounts of radioactivity (26% of the dose in 4h) were eliminated in bile as [14C]trimophonium glucuronide alone. The quantitative excretion of this metabolite in Gunn rat bile was about ten times that in normal animals. 4. It is proposed that the biochemical lesion in the homozygous Gunn rat may indirectly affect the biliary transport of exogenous glucuronides across the canalicular membrane.

scholarly journals Urobilinogen-i is a major derivative of bilirubin in bile of homozygous Gunn rats

1990 ◽  
Vol 268 (1) ◽  
pp. 181-185 ◽  
Author(s):  
P Kotal ◽  
J Fevery
Keyword(s):  
Wistar Rats ◽  
Wistar Rat ◽  
Intestinal Lumen ◽  
Freezing And Thawing ◽  
Gunn Rat ◽  
Chromatography Analysis ◽  
Gunn Rats ◽  
Intestinal Origin ◽  
Labelled Compound ◽  
Rat Bile

Gunn rats lack bilirubin UDP-glycosyltransferases, but diazo-negative derivatives of bilirubin have been described in their bile. In order to investigate this alternative disposal of bilirubin, crude bile samples from Gunn and Wistar rats were directly analysed by h.p.l.c. Besides bilirubin (in Gunn rats) or its glycosides (in Wistar rats), two major compounds were detected. A yellow one corresponded to the previously documented vitamin B-2 and was equally prominent in Gunn rats or Wistar-rat bile. The other compound was colourless, but on standing in contact with air it was spontaneously oxidized to a pinkish-yellow pigment. It was far more prominent in Gunn-rat bile. Analysis of bile obtained after intravenous injection of [14C]bilirubin to Gunn rats demonstrated that this compound was highly labelled. Freezing and thawing of the bile resulted in the formation of a series of diazo-negative derivatives, demonstrating that the original compound was quite labile. Spectral (adsorption and fluorescent) and chromatographic (h.p.l.c., t.l.c. and paper chromatography) analysis of the oxidized form of the labelled compound allowed its identification as urobilin-i. The colourless compound secreted in bile was urobilinogen-i. Administration of neomycin and bacitracin to Gunn rats or gut resection suppressed the biliary excretion of urobilinogen and thus confirmed its intestinal origin. Urobilinogen seems thus to represent the major bilirubin derivative present in Gunn-rat bile. Its breakdown products might represent the so-far-unidentified diazo-negative polar bilirubin derivatives. Since only a small amount of bilirubin is present in Gunn-rat bile, the urobilinogen formed in the intestinal lumen seems to be derived from bilirubin reaching the gut via routes other than the biliary one.

Bilirubin Content and 4-Nitrophenol Glucuronosyltransferase Activity in Gunn Rat Liver

1984 ◽  
Vol 66 (4) ◽  
pp. 481-486 ◽  
Author(s):  
Chantal Celier ◽  
Armelle Foliot
Keyword(s):  
Wistar Rats ◽  
Microsomal Fraction ◽  
Microsomal Protein ◽  
Protein Ratio ◽  
Gunn Rat ◽  
Gunn Rats ◽  
Hepatic Monooxygenase ◽  
Liver Microsomal Fraction ◽  
Low Activity ◽  
Lipid Diet

1. The purpose of this study was to determine whether the hepatic content of bilirubin could influence liver 4-nitrophenolglucuronosyltransferase (4-NP-GT) in the Gunn rat. 2. In animals fed on a 45% lipid diet, compared with rats fed on a normal lipid diet (3%), the bilirubin content of the hepatic microsomal fraction decreased and the bilirubin/protein ratio was reduced. 4-NP-GT activities were comparable in both groups. 3. Administration of clofibrate to Gunn rats greatly enhanced the bilirubin content of liver microsomal fraction. Since this treatment raised the microsomal protein content, the bilirubin/protein ratio was not modified. No significant change in 4-NP-GT was noted. 4. After bilirubin perfusion in Gunn and Wistar rats, no change was observed in hepatic monooxygenase activities or in 4-NP-GT, although the bilirubin/protein ratio was dramatically increased in the microsomal fraction. 5. From these results the low activity of liver 4-NP-GT in Gunn rats does not seem directly related to the hepatic content of bilirubin.

Hepatocyte cotransport of taurocholate and bilirubin glucuronides: role of microtubules

1988 ◽  
Vol 255 (1) ◽  
pp. G121-G131 ◽  
Author(s):  
J. M. Crawford ◽  
J. L. Gollan
Keyword(s):  
Biliary Excretion ◽  
Bile Salts ◽  
Intracellular Transport ◽  
Liver Microsomes ◽  
Bile Pigment ◽  
Significant Shift ◽  
Physical Interaction ◽  
Rat Liver Microsomes ◽  
Canalicular Membrane ◽  
Gunn Rats

Modulation of bile pigment excretion by bile salts has been attributed to modification of canalicular membrane transport or a physical interaction in bile. Based on the observation that a microtubule-dependent pathway is involved in the hepatocellular transport of bile salts, we investigated the possibility that bilirubin glucuronides are associated with bile salts during intracellular transport. Experiments were conducted in intact rats (basal) or after overnight biliary diversion and intravenous reinfusion of taurocholate (depleted/reinfused). All rats were pretreated with intravenous low-dose colchicine or its inactive isomer lumicolchicine. Biliary excretion of radiolabeled bilirubin glucuronides derived from tracer [14C]bilirubin-[3H]bilirubin monoglucuronide (co-injected iv) was unchanged in basal rats but was consistently delayed in depleted/reinfused rats. This was accompanied by a significant shift toward bilirubin diglucuronide formation from both substrates. In basal Gunn rats, with deficient bilirubin glucuronidation, biliary excretion of intravenous [14C]bilirubin monoglucuronide-[3H] bilirubin diglucuronide was unaffected by colchicine but was retarded in depleted/reinfused Gunn rats. Colchicine had no effect on the rate of bilirubin glucuronidation in vitro in rat liver microsomes. We conclude that a portion of the bilirubin glucuronides generated endogenously in hepatocytes or taken up directly from plasma may be cotransported with bile salts to the bile canalicular membrane via a microtubule-dependent (vesicular?) mechanism.

scholarly journals Comparison of the biliary excretion of the four isomers of bilirubin-IX in Wistar and homozygous Gunn rats

1977 ◽  
Vol 164 (1) ◽  
pp. 229-236 ◽  
Author(s):  
N Blanckaert ◽  
K P M Heirwegh ◽  
Z Zaman
Keyword(s):  
Intravenous Administration ◽  
Biliary Excretion ◽  
Wistar Rats ◽  
Pyrrole Ring ◽  
Carboxyl Groups ◽  
Carboxyl Group ◽  
Bile Pigments ◽  
Gunn Rats

The biliary excretion of the four isomers of bilirubin-IX was studied in Wistar rats (JJ) and homozygous Gunn rats (jj). Synthetic preparations of 14C-labelled pigments were used. 1. After intravenous administration, the alpha-isomer was rapidly excreted in conjugated form in bile of Wistar rats. In Gunn rats excretion was insignificant. In contrast, both rat species promptly excreted the non-alpha-isomers at rates that were comparable with that found for bilirubin-IXalpha in Wistar rats. 2. In normal rats about 16% of the beta- and delta-isomers and at least 50% of the gamma-isomer were excreted as ester conjugates of the injected parent bile pigments. Conjugation of the beta- and delta-isomers had occurred exclusively at the carboxyl groups of pyrrole ring D and C respectively. For bilirubin-IXgamma no preference for any carboxyl group could be established. 3. In homozygous Gunn rats the non-alpha-isomers were apparently excreted chemically unaltered. This suggests that, as for bilirubin-IXalpha, conjugation of the non-alpha-isomers is also deficient in Gunn rats.

Low Serum Levels of Fibroblast Growth Factor 2 in Gunn Rats: A Hyperbilirubinemia Animal Model of Schizophrenic Symptoms

2020 ◽  
Vol 19 (7) ◽  
pp. 503-508
Author(s):  
Maiko Hayashida ◽  
Sadayuki Hashioka ◽  
Kenji Hayashida ◽  
Shoko Miura ◽  
Keiko Tsuchie ◽  
...  
Keyword(s):  
Animal Model ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Wistar Rats ◽  
Serum Levels ◽  
Significant Negative Correlation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Normal Strain ◽  
Fibroblast Growth ◽  
Gunn Rats

Background: Fibroblast growth factor (FGF) 2 (also referred to as basic FGF) is a multifunctional growth factor that plays a pivotal role in the pro-survival, pro-migration and pro-differentiation of neurons. Method: Because alterations in FGF2 levels are suggested to contribute to the pathogenesis schizophrenia, we investigated serum levels of FGF2 in the Gunn rat, a hyperbilirubinemia animal model of schizophrenic symptoms. Results: The enzyme-linked immunosorbent assay showed that the serum levels of FGF2 in Gunn rats were 5.09 ± 0.236 pg/mL, while those in the normal strain Wistar rats were 11.90 ± 2.142 pg/mL. The serum FGF2 levels in Gunn rats were significantly lower than those in Wistar rats. We also measured serum levels of unconjugated bilirubin (UCB) and found a significant negative correlation between UCB and FGF2 at serum levels in all the rats studied. Conclusion: Since it is known that FGF2 regulates dopaminergic neurons and have anti-neuroinflammatory effects, our finding suggests that low FGF2 levels may contribute to the pathogenesis of schizophrenia, in which disbalanced dopamin-ergic signaling and neuroinflammation are supposed to play certain roles.

Biliary excretion of digitoxin and its metabolites in young and old male wistar rats

1982 ◽  
Vol 17 (6) ◽  
pp. 407-416 ◽  
Author(s):  
K KITANI ◽  
S KANAI ◽  
Y SATO ◽  
M NOKUBO
Keyword(s):  
Biliary Excretion ◽  
Wistar Rats ◽  
Male Wistar Rats

Biliary excretion of synthetic sex steroids in heterozygous and homozygous gunn rats

Life Sciences ◽  
1978 ◽  
Vol 23 (10) ◽  
pp. 1053-1056 ◽  
Author(s):  
D.J. Back ◽  
A.M. Breckenridge ◽  
Francesca E. Crawford ◽  
Karen J. Cross ◽  
M.L'E. Orme ◽  
...  
Keyword(s):  
Sex Steroids ◽  
Biliary Excretion ◽  
Gunn Rats

Glucagon induces biliary protein excretion in guinea pigs

1993 ◽  
Vol 264 (5) ◽  
pp. G961-G966
Author(s):  
R. Lenzen ◽  
N. Tavoloni
Keyword(s):  
Biliary Excretion ◽  
Guinea Pigs ◽  
Lysosomal Enzymes ◽  
Fluid Transport ◽  
Dependent Manner ◽  
Canalicular Membrane ◽  
Protein Excretion ◽  
Endogenous Protein ◽  
Camp System ◽  
Protein Output

This study was done to determine glucagon's effect on protein biliary excretion in anesthetized, bile duct-cannulated guinea pigs. Glucagon (1.4 nmol.min-1.kg-1) induced choleresis and increased protein biliary concentration from 0.12 +/- 0.04 to 0.20 +/- 0.6 mg/ml and protein output from 22.8 +/- 3.8 to 54.5 +/- 16.1 micrograms.kg-1.min-1. Protein biliary excretion increased during the first 10 min of glucagon infusion and progressively declined thereafter. Biochemical analysis of biliary protein revealed that the increase could be accounted for primarily by an increase in the lysosomal enzymes acid phosphatase and beta-glucuronidase. Biliary excretion of the canalicular membrane enzymes 5'-nucleotidase and alkaline phosphatase only modestly increased, whereas that of [14C]sucrose, a marker of paracellular fluid transport, was unaffected. On the other hand, glucagon enhanced biliary entry of horseradish peroxidase in a fashion similar to that observed with total endogenous protein. These effects were mediated by the adenosine 3',5'-cyclic monophosphate (cAMP) system, since infusion of dibutyryl-cAMP at 0.5 mumol.kg-1.min-1 increased bile flow and biliary protein excretion in a time-dependent manner, as observed with glucagon. Glucagon's failure to sustain enhanced protein biliary output was not due to declining hepatic concentrations of cAMP or to depletion of hepatocellular lysosomal enzymes. These studies provide evidence that glucagon stimulates biliary excretion of protein in guinea pigs that can be accounted for by biliary discharge of enzyme originating from the canalicular membrane and, primarily, from the lysosomal compartment. Although the precise mechanism(s) underlying these effects remains to be elucidated, it is suggested that the increase in canalicular membrane enzyme excretion is due to glucagon's effect on exocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

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