Search PubMed⌕ Search

Biomedical subjects

Z Gregus

Publications and source records attributed to Z Gregus.

At least 55 records · Page 3Linked to original sources
PubMed1985

Role of glutathione and hepatic glutathione S-transferase in the biliary excretion of methyl mercury, cadmium and zinc: a study with enzyme inducers and glutathione depletors.

The effect of hepatic glutathione (GSH) depletion and enzyme induction on hepatic glutathione S-transferase (GST) activity, biliary excretion of GSH, methyl mercury, cadmium and zinc was studied in rats. The GSH depletors, methyl iodide and diethyl maleate, did not influence hepatic GST activity but, depending on the substrate used, benzo(a)pyrene, phenobarbital, pregnenolone-16 alpha-carbonitrile (PCN) and trans-stilbene oxide (TSO) increased it by 16-33, 44-89, 53-97 and 208-279%, respectively. GSH depletors decreased (-88%), benzo(a)pyrene and TSO did not affect, phenobarbital and PCN increased (+113 and +149%) the transport of GSH into bile. The biliary excretion of methyl mercury, cadmium and zinc was reduced by GSH depletors (-97, -74 and -93%), and enhanced by phenobarbital (+139, +280 and +220%) and PCN (+150, +121 and +160%). Treatment with benzo(a)pyrene and TSO did not affect the excretion of methyl mercury and zinc into bile, but decreased that of cadmium. These results do not provide evidence for the role of hepatic GST but strongly support the importance of biliary GSH excretion in the hepatobiliary transport of methyl mercury, cadmium and zinc. It is assumed that phenobarbital and PCN enhance the biliary excretion of these metals by increasing the transport of GSH, the carrier molecule, from liver to bile.

Animals↗
PubMed1983

Hepatic phase I and phase II biotransformations in quail and trout: comparison to other species commonly used in toxicity testing.

The ability of quail and trout to perform a number of representative phase I and phase II biotransformations was examined. To facilitate interspecies comparisons, metabolism of the same substrates was examined simultaneously under uniform conditions for rat, mouse, rabbit, guinea pig, cat, and dog. Both nonmammalian species can metabolize four representative substrates of phase I mixed-function oxidases and one substrate of epoxide hydrolase, though activity tended to be lower than that of the mammals. Important differences in the conjugative pathways were also noted. Among these differences were the quail's relative deficiency in glutathione conjugation and the trout's low ability to conjugate sulfate compounds. Trout liver UDP-glucuronosyltransferase activity was remarkably high toward testosterone and bilirubin, while quail liver formed glucuronides of naphthol, p-nitrophenol, and digitoxigenin-monodigitoxoside. Also noteworthy was the high N-acetyltransferase activity of both quail and trout toward isoniazid, beta-naphthylamine, and 2-aminofluorene. Differences in substrate specificity for a given enzymatic pathway may be an indication that multiple forms of drug metabolizing systems also occur in these nonmammalian species. Observation of several hundred- or even thousand-fold differences between species in their enzyme activities for certain substrates under uniform conditions re-emphasizes the need for caution in extrapolation of xenobiotic metabolism from one species to another.

Acetylation↗
PubMed1983

Depletion of hepatic uridine diphosphoglucuronic acid decreases the biliary excretion of drugs.

Hepatic levels of uridine diphosphoglucuronic acid (UDPGA) in rats decreased substantially (greater than 80%) 40 min after galactosamine (GAL) (600 mg/kg i.p.) or after 1 hr of diethyl ether (DE) narcosis. Biliary excretion of several cholephils requiring glucuronidation before excretion was reduced by GAL 76, 62, 92, 90 and 97% for bilirubin, diethylstilbestrol, iopanoic acid, phenolphthalein and valproic acid, respectively. GAL treatment caused delayed plasma clearances of the parent compounds and reductions in plasma concentrations and biliary excretions of glucuronide conjugates. The degree of this reduction was related to the maximal excretion rate of the individual compounds. For phenolphthalein glucuronide and phenol-3,6-dibromphthalein disulfonate, which do not undergo conjugation, GAL had no effect on their biliary excretion. DE-induced UDPGA depletion had no effect on phenolphthalein glucuronide excretion but reduced that of phenol-3,6-dibromphthalein disulfonate 25%. DE did not affect the plasma elimination or biliary secretion of phenolphthalein. Of the other cholephils requiring conjugation, DE reduced the excretion of bilirubin, diethylstilbestrol, iopanoic acid and valproic acid by 41, 29, 76 and 28%, respectively. DE decreased the plasma elimination of the parent compounds and the appearance of the conjugates in both plasma and bile. Reduction of glucuronide excretion into bile was less pronounced at higher doses of the cholephilic anions. Neither treatment reduced in vitro hepatic UDP-glucuronosyltransferase activity toward these substrates or substantially altered extrahepatic UDPGA concentrations. Thus, both GAL and DE decreased UDPGA to similar concentrations, but the biliary excretion of compounds requiring glucuronidation before secretion was depressed to a greater extent by GAL.

Animals↗
PubMed1982

The influence of cadmium on the biliary excretion of eosine and bromsulphthalein and on microsomal monooxygenase activities in the rat.

Cadmium sulfate x 8/3 H2O (0.3, 0.6, 1.5 and 2.0 mg/kg) administered simultaneously with eosine and bromsulphthalein (120 mumol/kg i.v.) did not significantly change the biliary excretion of the dyes. After a 3 days pretreatment with 2.0 mg/kg CdSO4 i.p. a body weight loss and an increase in the relative liver weight when calculated on body weight were observed together with an enhanced bile flow, but the excretion of the dyes was not markedly influenced. Ethylmorphine N-demethylation and ethoxycoumarin O-deethylation activities as well as microsomal cytochrome P-450 concentration were diminished by about 50%. It can be concluded that in male rats the hepatic microsomal monooxygenase system is more sensitive towards cadmium than the hepatic transport system for organic anions.

Animals↗
PubMed1982

Role of ligandin as a binding protein and as an enzyme in the biliary excretion of sulfobromophthalein.

The effect of butylated hydroxyanisole (BHA; 600 mg/kg i.p. daily, for 10 days) and trans-stilbene oxide (TSO; 400 mg/kg i.p. daily, for 4 days) on the in vitro hepatic activity of glutathione transferases, the hepatic content of organic anion binding proteins and the plasma disappearance and biliary excretion of sulfobromophthalein (BSP), phenol-3,6-dibromsulphthalein disulfonate and [3H]ouabain was investigated in mice (BHA) and rats (TSO). Both BHA and TSO increased glutathione transferase activity toward BSP (360 and 200%), hepatic ligandin content (160 and 120%) and the biliary excretion of BSP (370 and 85%). BSP-glutathione excretion was enhanced, indicating that BSP conjugation was also stimulated in vivo. In contrast to BSP, biliary excretion of phenol-3,6-dibromsulphthalein disulfonate and organic anion which is not biotransformed but binds to ligandin, was unaltered or slightly increased (29%) after BHA or TSO treatment, respectively. TSO administration also did not affect the excretion of ouabain, a compound that neither binds to ligandin nor is biotransformed before excretion. Induction of ligandin failed to influence the initial disappearance of BSP, phenol-3,6-dibromsulphthalein disulfonate or ouabain from plasma, suggesting that induction had no marked effect on the hepatic uptake of these compounds. These studies suggest that ligandin plays a more important role in the biliary excretion of BSP due to its enzymatic rather than its binding properties.

Animals↗
PubMed1982

Effect of bile acids on the biliary excretion of amaranth and the respiration of liver mitochondria.

The effects of lithocholic acid (LCA), chenodeoxycholic acid (CDCA), deoxycholic acid (DOCA), cholic acid (CA) and dehydrocholic acid (DHCA) on the biliary excretion of amaranth (AM) in rats and on the respiration of isolated liver mitochondria were investigated. Bile acids diminished the biliary excretion of AM, and in vitro they enhanced the state 4 mitochondrial respiration and inhibited DNP- and ADP-stimulated oxygen consumption. The ID50 values (mumol/kg i.v.) and I50 concentrations (X 10(-5) M) of the bile acids for inhibiting AM excretion and ADP-stimulated mitochondrial respiration, respectively, were as follows: for LCA 16 and 3.3, for CDCA 160 and 24, for DOCA 230 and 31, for CA 680 and 105, and for DHCA 700 and 260. LCA, CDCA and DOCA inhibited the biliary excretion of AM uncompetitively. It is concluded that the toxic effect of LCA, CDCA and DOCA on mitochondria might play a role in their inhibitory action on the biliary transport of AM.

Amaranth Dye↗
PubMed1981

The influence of bile acids on biliary excretion of indocyanine green in rats of different ages.

In rats of different ages bile flow and biliary excretion of indocyanine green (ICG) were estimated in dependence on bile acid excretion. In 20, 30, 60 and 180 day old rats bile acid excretion was diminished to a quarter of the control by pretreatment with cholestyramine (1.5 g/kg b.wt.). To enhance bile acid excretion, taurocholate sodium (TC, 50 mg/kg b.wt.) was given together with the dye. Bile acid depletion diminished the bile flow to a greater extent in young rats, which were found to have a higher bile acid dependent fraction of canalicular bile flow (60%) compared to 60 (35%) and 180 day old rats (20%). After bile acid depletion the decrease in ICG excretion was more pronounced in 30 and 60 day old rats which exhibit highest dye excretion rates. TC was able to enhance the bile flow in all age groups investigated, however, the ICG excretion was enhanced only in adult animals. Our results indicate that the bile acid dependence of the hepatobiliary transport of ICG is influenced by age.

Age Factors↗
PubMed1980

Effects of barbiturates on the hepatic cytochrome P-450 dependent enzyme system and biliary excretion of exogenous organic anions in rats.

Effect of pretreatment (150 mumol/kg i.p. twice daily for 5 days) wtih six barbiturates (barbital, butobarbital, pentobarbital, amobarbital, phenobarbital and thiopental) on the hepatic microsomal drug methabolizing enzyme system and biliary excretion of bromcresol green and bromsulphthalein-glutathione conjugate has been investigated in rats. All six barburates produced microsomal induction. Phenobarbital, thiopental, barbital and butobarbital increased liver weight, biliary flow and biliary excretion of bromcresol green and bromsulphthalein-glutathione conjugate, however, pentobarbital and amobarbital were ineffective in these parameters. Our results seem to indicate that the enhanced biliary excretion of exogenous anions produced by barbiturates is independent of microsomal enzyme induction.

Animals↗
PubMed1980

Choleric potencies of some bile acids and their effect on biliary excretion of eosin in the rat.

The effect of bile acids on bile flow and biliary excretion of eosine (80 mg/kg i.v.) has been investigated in anaesthetized (urethane 1.2 g/kg i.p.), bile duct-cannulated female Sprague-Dawley rats weighing 180--220 g. The biliary flow was significantly enhanced by cholic acid, glycocholic acid, taurocholic acid, deoxycholic acid, chenodeoxycholic acid and dehydrocholic acid (each in a dose of 100 mg/kg i.v.). However, it was definitely decreased by lithocholic acid (10o mg/kg i.v.). The biliary excretion of eosine was increased by cholic acid and dehydrocholic acid, whereas it was decreased by chenodeoxycholic acid and lithocholic acid. Deoxycholic acid, glycocholic acid and taurocholic acid had no effect on the biliary excretion rate of eosine. These results suggest that no parallelism exists between the choleretic effect of bile acids and their influence on the biliary excretion of eosin.

Animals↗
PubMed1980

Qualitative differences in the hepatobiliary transport of sulfobromophthalein (BSP) and its glutathione conjugate (BSP-GSH).

The effect of phenobarbital pretreatment (PB; 75 mg/kg i.p. once daily for 5 days) and the simultaneous administration of taurocholate (TC; 200 mumol/kg i.v.), eosin(EO; 40-160 mumol/kg i.v.) and iodoxamic acid (IA; 125--500 mumol/kg i.v.) on the hepatic uptake and biliary excretion of BSP (30--120 mumol/kg i.v.) and BSP--GSH (40--160 mumol/kg i.v.) was investigated on diethyl maleate (DEM)-pretreated rats. The biliary excretion of BSP was not influenced by PB and EO, while it was increased by TC and decreased by IA. In contrast, the excretion of BSP--GSH was not influenced by TC or IA, it was stimulated by PB and inhibited by EO. In the different experimental conditions the hepatic uptake of BSP and BSP--GSH changed similarly: PB did not influence, TC, EO and IA decreased the accumulation of BSP and BSP--GSH in the liver. These results indicate that qualitative differences exist in the hepatobiliary transport of BSP and BSP--GSH, which manifest themselves following their hepatic uptake.

Animals↗
PubMed1980

Effect of cholestyramine-induced bile acid depletion on the hepatobiliary transport of cholephilic organic anions in rats.

Four hours after oral administration of cholestyramine (1.0 g/kg) the biliary output of bile acids decreased to 21 per cent of the control value. The biliary excretion of indocyanine green (ICG; 15--60 mumol/kg i.v.), rose bengal (RB; 15--60 mumol/kg i.v.), bromsulphthalein (BSP; 15--60 mumol/kg i.v.), bromcresol green (BCG;15--60 mumol/kg i.v.) and eosine (EO; 30--120 mumol/kg i.v.) was considerably depressed by cholestyramine pretreatment. The extent and duration of the reduction in the biliary excretion of organic anions in response to bile acid depletion were found to increase with their doses. In contrast, the biliary excretion rates of bromsulphthalein-glutathione conjugate (BSP-GSH; 60--240 mumol/kg i.v.) and amaranth (AM; 60--240 mumol/kg i.v.) remained unchanged following bile acid depletion. The hepatic uptake of the cholephilic agents investigated was not affected by bile acid depletion. It is concluded that the biliary excretion rates of ICG, RB, BSP, BCG and EO are dependent on the excretion rates of endogenous bile acids. The hepatic transport rates of BSP-GSH and AM, however, seem to be relatively insensitive to the biliary output of endogenous bile salts.

Animals↗