The conjugative metabolism of 4-methylumbelliferone and deconjugation to the parent drug examined by isolated perfused liver and in vitro liver homogenate of rats.

1989 ◽  
Vol 37 (2) ◽  
pp. 475-480 ◽  
Author(s):  
Seiji MIYAUCHI ◽  
Yuichi SUGIYAMA ◽  
Tatsuji IGA ◽  
Manabu HANANO
Keyword(s):  
Liver Homogenate ◽  
Parent Drug ◽  
Perfused Liver ◽  
Isolated Perfused Liver

scholarly journals Effect of thyroid state on cyclic AMP-mediated induction of hepatic phosphoenolpyruvate carboxykinase

1985 ◽  
Vol 226 (1) ◽  
pp. 67-73 ◽  
Author(s):  
W Höppner ◽  
W Süssmuth ◽  
H J Seitz
Keyword(s):  
Cyclic Amp ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Close Correlation ◽  
Perfused Liver ◽  
Thyroid State ◽  
Fed State ◽  
Isolated Perfused Liver ◽  
Translatable Mrna

Hepatic phosphoenolpyruvate carboxykinase (PEPCK) is significantly increased in the hyperthyroid starved rat, and moderately decreased in the hypothyroid starved rat. As tri-iodothyronine by itself has only a small and sustained effect on the induction of this enzyme, as was previously shown in the isolated perfused organ, the effect of hypo- and hyper-thyroidism on the increase in cytosolic PEPCK provoked by dibutyryl cyclic AMP (Bt2cAMP) was investigated in vivo and in the isolated perfused liver. Compared with euthyroid fed controls, in hypothyroid fed rats Bt2cAMP provoked in 2 h only a small increase in translatable mRNA coding for PEPCK. In contrast, in hyperthyroid animals PEPCK mRNA as measured by translation in vitro was already increased in the fed state, and further enhanced by Bt2cAMP injection to values as in euthyroid controls. Under all thyroid states a close correlation between PEPCK mRNA activity and PEPCK synthesis was observed. In the isolated perfused liver from the hyperthyroid fed rat, the increase in PEPCK provoked by Bt2cAMP or Bt2cAMP + isobutylmethylxanthine was considerably enhanced compared with those obtained in livers of hypothyroid rats. Also, adrenaline provoked a stimulated induction of PEPCK in hyperthyroid rats compared with hypothyroid rats. To summarize, our data indicate that the primary action of thyroid hormones on the synthesis of hepatic cytosolic PEPCK is to accelerate the cyclic AMP- or adrenaline-induction of the enzyme, acting primarily at a pretranslational level.

Brain Targeting of anti-HIV Nucleosides: Ether Prodrugs of 3′-Azido-2′,3′-Dideoxyuridine (AZdU) and 3′-Azido-3′-Deoxythymidine (AZT)

1993 ◽  
Vol 4 (5) ◽  
pp. 263-269 ◽  
Author(s):  
K. J. Doshi ◽  
Q. Islam ◽  
J. M. Gallo ◽  
F. D. Boudinot ◽  
L. Hsieh ◽  
...  
Keyword(s):  
Liver Homogenate ◽  
Parent Drug ◽  
Brain Targeting ◽  
Mouse Serum ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Time Curve ◽  
Drug Concentrations ◽  
Anti Hiv

In an effort to increase the brain delivery of anti-HIV nucleosides, 5-0-benzyl and glucose derivatives of 3′-azido-2′,3′-dideoxyuridine (AZdU or CS-87) and 3′-azido-3′-deoxythymidine (AZT) were synthesized. In vitro stability and pharmacokinetic studies in mice were conducted with benzyl AZdU (BzlAZdU), benzyl AZT (BzlAZT), and glucose AZdU (GAZdU) prodrugs. In vitro studies indicated that the prodrugs were stable in phosphate buffer (pH 7.4), human serum and mouse serum. In mouse brain homogenate, the degradation half-lives for BzlAZdU, BzlAZT, and GAZdU were 1.66, 2.06, and 0.98 h, respectively, and in liver homogenate the degradation half-lives were 0.49, 0.29, and 1.97h, respectively. Following intravenous administration of BzlAZdU, BzlAZT, or GAZdU to mice, prodrug and parent drug concentrations were measured in serum and brain by HPLC, and pharmacokinetic parameters determined. The brain:serum area under the concentration time-curve (AUC) ratio, a parameter indicative of prodrug uptake into brain, was 0.55 for BzlAZdU and 0.56 for BzlAZT, compared to 0.05–0.08 when the parent drugs AZdU and AZT were administered intravenously. GAZdU had poor brain penetration, achieving brain concentrations of only 5% of the serum concentrations. Parent drug concentrations in brain were, for the most part, not detected after administration of any of the prodrugs. Consistent with in vitro data, it is apparent that the prodrugs were converted to metabolites other than the parent drug species.

Influence of hepatic taurine concentration on bile acid conjugation with taurine.

1977 ◽  
Vol 232 (1) ◽  
pp. E75 ◽  
Author(s):  
W G Hardison ◽  
J H Proffitt
Keyword(s):  
Bile Acid ◽  
Cholic Acid ◽  
Sodium Cholate ◽  
Total Bile Acid ◽  
Perfused Liver ◽  
Taurine Concentration ◽  
Isolated Perfused Liver ◽  
Liver Homogenates

In vitro, addition of taurine to liver homogenates increases the proportion of cholic acid conjugated with taurine. In the present study, the relation between hepatic taurine concentration and the proportion of infused sodium cholate conjugated with taurine was studied in the whole organ. The isolated perfused liver was studied to eliminate possible transfer of taurine to or from the large extrahepatic poosl present in vivo. During cholate infusion, the proportion of taurocholate excreted in bile decreased, and the proportion of glycocholate increased in a complementary fashion. Infusion of taurine with cholate prevented these changes. Hepatic taurine concentration, calculated from measured hepatic taurine concentrations before and at the end of cholate infusion, fell. Fall in proportion of total bile acid excreted as taurocholate was most rapid at low hepatic taurine concentrations between about 1.4 and 0.65 mumol/g liver. Hepatic taurine concentrations is a major determinant of the proportion of bile acid conjugated with taurine.

scholarly journals Metabolic fates of diethylstilboestrol sulphates in the rat

1977 ◽  
Vol 164 (2) ◽  
pp. 423-430 ◽  
Author(s):  
P A Barford ◽  
A H Olavesen ◽  
C G Curtis ◽  
G M Powell
Keyword(s):  
Rat Liver ◽  
Whole Body ◽  
Perfused Liver ◽  
Isolated Perfused Liver

The metabolic fates and modes of excretion of diethylstilboestrol mono[35S]sulphate and diethylstilboestrol di[35S]sulphate were studied in the rat. Both of the esters were desulphated to some extent in vivo. In addition, significant amounts of radioactivity appeared in the bile as diethylstilboestrol mono[35S]sulphate monoglucuronide. The percentage of the dose appearing in bile as the diconjugate was substantially greater in experiments with diethylstilboestrol mono[35S]sulphate than with diethylstilboestrol di[35S]sulphate. Whole-body radioautography and studies with isolated perfused liver confirmed the liver as the major metabolic organ for both esters. When the metabolite diethylstilboestrol mono[35S]sulphate monoglucuronide isolated from the bile was reinjected, it was excreted in the bile unchanged. Studies in vitro demonstrated that both esters were substrates for arylsulphatase C with Km values in the range 52-76 micrometer. The metabolic fates and modes of excretion of the esters are discussed in relation to the enzyme complement of rat liver.

In Vitro Diabetogenic Effect of Cadmium on Liver

2017 ◽  
Vol 8 (01) ◽  
Author(s):  
Agung Biworo ◽  
Dwi Rezki Amalia ◽  
Gratianus Billy Himawan ◽  
Lisda Rizky Amalia ◽  
Valentina Halim ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Liver Homogenate ◽  
Liver Cells ◽  
Male Rats ◽  
Glycogen Level ◽  
Liver Sample ◽  
Km Value ◽  
Cd Exposure ◽  
Menten Constant

The objectives of this study were to determine the effect of cadmium (Cd) on glucose metabolism disruption in liver cells homogenate in vitro. The glucose metabolism disruption was analyzed by measuring the level of liver glucose, glycogen and methylglyoxal (MG), and the activity of glucokinase activity. In this experiment, a liver sample was taken from male rats (Rattus novergicus). Samples then homogenized and divided into four groups with; C served as control which contains liver homogenate only; T1 which contains liver homogenate + 0.03 mg/l of cadmium sulphate (CdSO4); T2 which contains liver homogenate + 0.3 mg/l of CdSO4; and T3 which contains liver homogenate + 3 mg/l of CdSO4. After treatment, liver glucose, glycogen, and MG levels, and glucokinase activity were estimated. The activity of liver glucokinase was estimated by measuring the Michaelis-Menten constant (Km) value. The results revealed that Cd exposure could significantly increase glucose and MG levels, the Km value of glucokinase, and decreased the glycogen level in liver cells (P>0.05). These results indicated that Cd exposure induced the disruption of glucose metabolism in the liver.

scholarly journals Hepatoprotective studies on methanolic extract fractions of Lindernia ciliata and development of qualitative analytical profile for the bioactive extract

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Praneetha Pallerla ◽  
Narsimha Reddy Yellu ◽  
Ravi Kumar Bobbala
Keyword(s):  
Methanolic Extract ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Liver Homogenate ◽  
Reducing Power ◽  
Hepatoprotective Activity ◽  
Total Phenolic ◽  
Effective Fraction

Abstract Background The objective of the study is to evaluate the hepatoprotective activity of methanolic extract fractions of Lindernia ciliata (LC) and development of qualitative analytical profile of the bioactive fraction using HPLC fingerprinting analysis. All the fractions of methanolic extract of Lindernia ciliata (LCME) are assessed for their total phenolic, flavonoid contents and in vitro antioxidant properties by using DPPH, superoxide, nitric oxide, hydroxyl radical scavenging activities and reducing power assay. Acute toxicity study was conducted for all the fractions and the two test doses 50 and 100 mg/kg were selected for the hepatoprotective study. Liver damage was induced in different groups of rats by administering 3 g/kg.b.w.p.o. paracetamol and the effect of fractions were tested for hepatoprotective potential by evaluating serum biochemical parameters and histology of liver of rats. The effective fraction was evaluated for its antihepatotoxic activity against D-Galactosamine (400 mg/kg b.w. i.p.) and in vivo antioxidant parameters viz., Glutathione (GSH), Melondialdehyde (MDA) and Catalase (CAT) levels are estimated using liver homogenate. Results Among all the fractions, butanone fraction of LCME, (BNF-LCME) has shown better hepatoprotective activity and hence it is selected to evaluate the antihepatotoxicity against D-GaIN. The activity of BNF-LCME is well supported in in vitro and in vivo antioxidant studies and may be attributed to flavonoidal, phenolic compounds present in the fraction. Hence, BNF-LCME was subjected to the development of qualitative analytical profile using HPLC finger printing analysis. Conclusions All the fractions of LCME exhibited significant hepatoprotective activity and BNF-LCME (50 mg/kg) was identified as the most effective fraction.

Loperamide inhibits the biliary excretion of irinotecan (CPT-11) in the rat isolated perfused liver

2005 ◽  
Vol 57 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Peter J. Tobin ◽  
Ying Hong ◽  
J. Paul Seale ◽  
Laurent P. Rivory ◽  
Andrew J. McLachlan
Keyword(s):  
Biliary Excretion ◽  
Perfused Liver ◽  
Isolated Perfused Liver

scholarly journals Thyroid hormone differentially augments biliary sterol secretion in the rat. I. The isolated-perfused liver model.

1992 ◽  
Vol 33 (10) ◽  
pp. 1459-1466
Author(s):  
RL Gebhard ◽  
BG Stone ◽  
JP Andreini ◽  
WC Duane ◽  
CD Evans ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Perfused Liver ◽  
Isolated Perfused Liver ◽  
Liver Model
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