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Biomedical subjects

W Klinger

Publications and source records attributed to W Klinger.

At least 109 records · Page 6Linked to original sources
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

[Effect of rimazolium (Probon) on biotransformation reactions in the rat].

Rimazolium inhibits ethylmorphine-N-demethylation and ethoxycoumarin-O-deethylation by rat liver homogenate when added in vitro in dependence on reaction differently, but marked effects are observed with high concentrations only (10(-3) mol). Both reactions are inhibited after administration of a high sedative dose (180 mg/kg) by 30-40%, after a non-sedative dose no inhibition could be observed. After a 4 d treatment both reactions were not influenced when investigated 24 h after the last administration, the induction by phenobarbital is inhibited in case of ethylmorphine-N-demethylation by rimazolium, but increased in case of ethoxycoumarin-O-deethylation.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1982

Age course and inducibility of dimethylnitrosamine N-demethylation in rat liver.

Dimethylnitrosamine (DMN)-N-demethylation by 10,000 x g liver supernatant follows a typical Michaelis-Menten kinetics with one apparent Km (4.0 . 10(-4) M) and V max (0.460 nmole/mg . min) of 30-day-old male rats. The investigation of hepatic DMN-N-demethylation in dependence on age reveals maximum activities in 30- to 60-day-old male rats. The demethylating enzyme activity is inducible by phenobarbital (PB), not by 3-methylcholanthrene (3-MC). Pretreatment of animals with PB plus 3-MC resulted in reduced inducibility compared with PB-pretreatment alone. Probably this is not due to an inhibition of PB-induction by 3-MC, but effected by PB residues in the liver tissue and in the incubation mixture. The elimination rate of PB in young rats seems to be retarded if high doses of the inducers PB and 3-MC are administered simultaneously. Additionally changes in inducible cytochrome P-450 subspecies have to be considered.

Aging↗
PubMed1982

Influence of allyl isopropyl acetamide on d-aminolevulinic acid and aminoacetone synthesis during postnatal development in rats.

In contrast to other groups we found an allyl isopropyl acetamide (AIA)-mediated induction of aminoketones (AK) in newborn rats. To further clarify this phenomenon, the development of d-amino-levulinic acid synthesis (ALAS) and aminoacetone synthesis (AAS) and their inducibility by AIA were determined during the first days of life, daily until the 5th day of life, and then up to an age of 240 days. Both ALAS and AAS decrease during the first 24 h of life; the inducibility of both is detectable 6 h after birth, and develops during the first day of life to reach maximal inducibility. Minimum values are observed between day 30-45 of life; thereafter a tendency of increasing basic activity (AAS) and constant (ALAS) or decreasing (AAS) inducibility is detectable.

5-Aminolevulinate Synthetase↗
PubMed1981

[Alcohol and drug biotransformation].

Alcohol is partly degraded by the same enzyme system which also metabolizes drugs. The competition with impairment of the biotransformation and prolongation of the half-life period of elimination for drugs was not yet proved human-pharmacologically. Alcohol is an enzymes inductor in relative small doses: the activity of enzymes of biotransformation increases also in man. In alcohol-induced enlargement of the liver and only slight (reversible) fat deposition the capacity of biotransformation is increased, the elimination accelerated. With increasing degree of severity of the liver defect by alcohol an increasing impairment of drug biotransformation and a clinically significant prolongation of the half-life periods of elimination develop. If in the multifactorial genesis of chronic liver diseases alcohol is not in foreground, so there is no enzyme induction effecting against the liver defect and restriction of the biotransformation and elimination of drugs become measurably already in liver defects of lower degree.

Biotransformation↗
PubMed1981

Influence of puromycin and chloramphenicol on aminoketone synthesis ( delta-aminolevulinic acid synthesis) induction by allylisopropylacetamide in rat liver.

In vitro induction of aminoketone synthesis (AKS) by allylisopropylacetamide (AIA) in liver slices from 30 day-old male rats was reversibly inhibited by puromycin (50 micrograms/ml incubation mixture). Normal AKS was initially stimulated and thereafter blocked. Chloramphenicol (350 micrograms/ml) inhibited AIA mediated induction of AKS only partially and only when added 1 h before AIA to the incubation mixture. In vivo puromycin (3 i.p. injections of 15 mg/kg in 1 h intervals) did not influence AKS or AIA mediated AKS induction in newborn rats, whereas chloramphenicol (500 mg/kg s.c. 30 min prior to AIA) inhibited AIA mediated AKS induction in newborn rats. In 40 day-old rats pretreatment with chloramphenicol completely inhibited AKS induction by 200 mg/kg AIA.

5-Aminolevulinate Synthetase↗
PubMed1981

Liver damage in rats by allylisopropylacetamide (AIA), an inducer of delta-aminolevulinic acid synthetase (ALAS).

Twentyfour hours after the intraperitoneal injection of a single dose of allylisopropylacetamide (AIA) in amounts of 100 mg/kg or more to 30-day old male Wistar rats, the livers of most of the animals showed an irregular yellow coloration and a fragile consistency. No macroscopic changes were detected following AIA doses of 25 or 50 mg/kg. Bromsulphthalein retention was not significantly increased after the administration of 25 mg/kg AIA, but distinctly enhanced after 400 mg/kg. Succinate-dehydrogenase-activity in liver homogenate was not altered after 25 mg/kg, but significantly decreased after 400 mg/kg. Ethylmorphine-N-demethylation activity was enhanced after small doses without increase of cytochrome P-450 (cyt. P-450) concentration and decreased after higher doses, accompanied by a remarkable cyt. P-450 loss. GPT activity in serum and liver was not altered after both 25 and 400 mg/kg AIA. GOT activity was slightly but significantly enhanced both in serum and liver after the high dose of 400 mg/kg. Thus in addition to the well-known cyt. P-450 destruction other signs of hepatotoxicity could be demonstrated.

5-Aminolevulinate Synthetase↗
PubMed1981

Influence of drugs on the bilirubin UDP-glucuronyltransferase activity and the concentration of Y and Z acceptor proteins in rat liver.

The aim of this paper is to report on the influence of phenobarbital, the combination of phenobarbital/nikethamide, the racemate and (+) isomer of methylphenobarbital on the activity of bilirubin UDP-glucuronyltransferase and the concentration of intrahepatic Y and Z protein in rats. The activity of bilirubin DP-glucuronyltransferase increased after the treatment in all groups. Pretreatment with phenobarbital/nikethamide resulted in the highest enzyme activity, using wet weight as reference. (+) Methylphenobarbital isomer as well as the racemate showed effects similar to those of phenobarbital. The concentration of hepatic Y acceptor protein increased in all pretreated groups by about 30%. The drugs did not increase the concentration of Z protein. The (+) isomer of methylphenobarbital seems better suited as an inductive drug in the prophylaxis of hyperbilirubinemia and in the treatment of nonconjugated hyperbilirubinemia than phenobarbital or phenobarbital/nikethamide since it has no sedative effect.

Animals↗
PubMed1981

The influence of 6-hydroxydopamine on the development and inducibility of drug metabolism in rat liver.

6-Hydroxydopamine (6-OHDA) pretreatment of rats in the first 4 days of life considerably enhances the low hepatic ethylmorphine N-demethylation rate in 9 and 16 day old rats, whereas the higher rates in adult rats are not influenced. After 6-OHDA treatment the age differences in ethylmorphine N-demethylation rate disappear. The induction of ethylmorphine N-demethylation by phenobarbital is markedly enhanced by neonatal 6-OHDA pretreatment in 16 to 60 day old rats, whereas in 9 day old rats this synergistic action is not detectable. Unlike ethylmorphine N-demethylation, hepatic 7-ethoxy-coumarin 0-deethylation rate is only slightly or not at all influenced by 6-OHDA pretreatment. The basic activities in 9 day and rats are enhanced, the induction by phenobarbital in the same age-group is decreased. In other age-groups neither basic activities nor inducibility are influenced by 6-OHDA pretreatment. Hepatic cytochrome P-450 concentrations in 33- and 60 day old control rats do not differ from those in 6-OHDA-pretreated animals. Phenobarbital treatment increases the P-450 content; this induction effect is enhanced after 6-OHDA pretreatment, but not as markedly as with ethylmorphine N-demethylation.

Age Factors↗
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

Hepatic nuclear free and engaged RNA-polymerases in young rats pretreated with 3-methylcholanthrene.

In 3-methylcholanthrene (3-MC)-pretreated young rats the free and engaged RNA polymerases were investigated in detail both in the nucleolar and nucleoplasmic fractions. Both functional forms of the nucleolar RNA polymerase (A) show a great stimulation. The maximum increase of the free form up to 235% compared with controls is obtained 24 h after 3-MC administration. The engaged fraction reaches its maximum later. The extranucleolar RNA polymerase (B) in its engaged form shows the maximum effect (160%) after 24 h, whereas the free form is at first diminished and later on increases steadily. The activation of RNA polymerase A and the interconversion process between the free and engaged form of RNA polymerase B seem to play a significant role in the 3-MC-mediated induction.

Amanitins↗
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

Influence of phenobarbital, chlorpromazine, progesterone and phenylbutazone on the biliary cholesterol excretion in rats.

Bile flow and biliary excretion of free cholesterol were estimated after single and/or repeated i.p. administration of phenobarbital (60 mg/kg b. w.), chlorpromazine (40 mg/kg b.w.), progesterone (50 mg/kg b.w.), and phenylbutazone (100 mg/kg b.w.) in male Wistar rats. The drugs enhanced the biliary cholesterol excretion after both single and repeated administration, whereas only phenobarbital and phenylbutazone pretreatment increased the bile flow. Bile acid excretion was concomitantly enhanced only after phenylbutazone pretreatment. These results suggest that cholesterol output in rats may be widely bile acid independent and can be influenced by different drugs.

Animals↗
PubMed1980

The influence of allyl isopropyl acetamide on d-aminolevulinic acid synthetase and cytochrome P-450.

Allyl isopropyl acetamide (AIA) is believed to destroy P-450 and to enhance the d-aminolevulinic acid synthetase (ALAS) activity by lowering the heme pool of the liver parenchymal cell, in this way weakening the negative feed back mechanism, which regulates ALAS synthesis at the translational level. Dose and time dependence of the AIA influence on cytochrome P-450 concentration and P-450 activity argues against this theory, supporting the hypothesis that AIA destroys P-450 only after administration of higher doses (> 300 mg/kg i. p.), but does not influence or even enhances P-450 concentration when given in lower doses which exert an increase in ALAS activity. 25--100 mg/kg AIA i. p. have no significant effect on ALAS activity, 200 mg/kg and higher doses up to 400 mg/kg cause dose-dependent increases in ALAS activity.

5-Aminolevulinate Synthetase↗