[Activity of alanine aminotransferase and sorbitol dehydrogenase in rat serum following loading with indocyanine green].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A Barth.
Explore the source record for details and available documents.
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.
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.
Quantitative structure activity analysis of the substrate types Ala-Ala-AR and Ala-Pro-AR containing different substituents in the aryl ring showed that the rate-limiting step in the hydrolysis of the alanine substrates by dipeptidyl peptidase IV occurs in th acylation reaction (kcat approximately k2). Probably, the tetrahedral intermediate of the acylation process has a real life time. The positive q-value of the Hammett-equation in k'cat suggests that the N-atom of the arylamide is charged more negatively in the transition state TI not equal to than in the original state TI. The analysis of the quantitative conformation activity relationship (QCAR) gives information on the steric situation in the tetrahedral intermediate of the acylation step near the transition state. The rate limiting step in the hydrolysis of the substrates of the proline type occurs in the deacylation reaction.
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.
Bile flow and biliary excretion of dihydroxy- and trihydroxy-bile acids have been determined in control, cholestyramine (250--2000 mg/kg p.os)- and aluminium hydroxide (250--2000 mg/kg p.os)-pretreated rats. Cholestyramine proved to be a more potent bile acid depleting agent than aluminium hydroxide. The depressing effect of cholestyramine on bile flow was also more significant than that of aluminium hydroxide. Cholestyramine-pretreatment seemed to be a suitable experimental model for the depletion of bile acids in rat bile.
Explore the source record for details and available documents.
It has been demonstrated that ordinary regression coefficients of a quantitative structure-activity equation depend strongly on the scaling both of the biological parameter and the explanatory variables (regressors). Even in the case of only two regressors this fact may lead to challengable interpretations regarding the relative performances of the explanatory variables, say physicochemical parameters. The use of standardized variables and, consequently, of standardized regression coefficients is proposed in order to get a better insight into the mechanistic features of the mode of action of the congeneric series under investigation. The procedure has been illustrated with examples adapted from the literature.
The influence of metyrapone on bile flow and excretion of mono-(MBA), di-(DBA) and trihydroxy-(TBA)-bile acids was investigated in adult male Wistar rats after single and repeated pretreatment. MBA were not found in the rat bile. Metyrapone administration (200 mg/kg b.w. i.p.) 1 h before onset of a 3-hour bile collection period diminished bile flow and excretion of DBA and TBA. The relation TBA/DBA was changed towards DBA. Similar results were found after repeated administration 12 h after the last metyrapone injection (4 x 50 mg/kg b.w. i.p. per day for 4 consecutive days). But 60 h after the last metyrapone administration bile flow and the excretion of TBA were enhanced and the TBA/DBA ratio was changed towards TBA. The possible influence of metyrapone on bile acid hydroxylation is discussed and compared with metyrapone action on hydroxylation of foreign compounds.
The relatively alanine-specific amino peptidase from Brassica napus hydrolyzes dipeptidyl-4-(phenylazo)-phenylamide according to a consecutive mechanism. Enzyme-kinetic studies of dipeptidyl-4-(phenylazo)-phenylamides carried out by means of spectrometrical procedures of measurement are only possible when the increase in the concentration of the fission product p-aminoazobenzene is recorded. For assessing the kinetic parameters of the intermediary steps of the hydrolysis of dipeptidyl-4-(phenylazo)-phenylamides a function is derived describing the dependence of the concentration of fission products of p-aminoazobenzene on reaction time. The satisfactory correspondence of the kinetic parameters calculated for the intermediary-originating substrate L-ala-4-(phenylazo)-phenylamide as substrate demonstrates the applicability of the procedure described in the present paper.
The hydroxylation of bile acids in rat liver microsomes in cyt P-450 dependent (Björkhem et al., 1975). To find out possible interactions between drugs and bile acid hydroxylation and/or active transport mechanisms we investigated the influence of the microsomal inhibitor metyrapon, the microsomal inducer phenobarbital and the intrahepatic cholestasis producing agents chlorpromazine, phenylbutazone and progesteron on bile flow and bile acid excretion. The excretion in monohydroxy (MBA), dihydroxy (DBA) and trihydroxy (TBA) bile acids were estimated in bile-fistula rats in three one hour periods. MBA, DBA and TBA were separated with thinlayer-chromatography and estimated fluorimetrically. Bile flow, bile acid excretion and relation TBA/DBA were influenced by acute and subchronic administration of the above mentioned drugs in different ways.
Bile flow and excretion of monohydroxy-, dihydroxy- and trihydroxy-bile acids (MBA, DBA and TBA) were estimated after acute and subacute phenobarbital and chlorpromazine pretreatment in 60-day-old male Wistar rats. Bile was collected in bile-fistula rats in three 1-hour periods. MBA were not detected. Neither single nor repeated ip. administration of different amounts of saline before bile sampling nor oral water supply within the bile collection period influenced the bile flow and excretion of DBA and TBA. Phenobarbital administration (60 mg/kg b.w. ip.) 2 hrs before bile sampling did not influence bile flow and bile acid (BA) excretion. After 3 days pretreatment with phenobarbital (3 X 60 mg/kg b.w. ip.) the bile flow was somewhat increased, BA-excretion was unchanged and the relation TBA/DBA diminished. Chlorpromazine administration (40 mg/kg b.w. ip.) 1,5 hrs before bile sampling decreased bile flow and BA excretion within the first collection period, whereas bile flow and BA excretion increased in the thrid collection period. No signs of cholestasis were observed after chlorpromazine pretreatment once a day for 3 days. Bile flow and BA excretion were increased and the relation TBA/DBA was unchanged.
Explore the source record for details and available documents.
Dipeptidyl-peptidase IV isolated from pig kidney microsomes catalyses hydrolysis in a number of dipeptidylaryl-amides of types L-AS-L-Ala-R and L-AS-L-Pro-R. Kinetic studies involving two competing substrates suggest the probable existence of a catalytic centre for both groups of substrates. The speed-determining steps in enzymatic hydrolysis differ in the order L-AS-L-Pro-R and L-AS-L-Ala-R. The secondary enzymatic deuterium-isotopic effects in the hydrolysis of L-Ala-L-Ala-2-d1-pNA are fixed at KHM/KDM = 1.24 and VHmax/VDmax = 1.27. The existence of an acyl-enzyme mechanism is considered likely.
Bile flow and excretion of monohydroxy-, dihydroxy- and trihydroxy bile acids (MBA, DBA and TBA) were estimated after acute and subacute progesterone and phenylbutazone pretreatment in adult male Wistar rats in three one-hour periods. Different pretreatment with sunflower oil did not influence bile flow and excretion of DBA and TBA. MBA were not detected. Different administration of progesterone and phenylbutazone did not significantly change the TBA/DBA ratio. Progesterone administration (50 mg/kg b. w. i. p.) 2 hours before bile sampling increased bile flow and bile acid excretion in the third one-hour period. After 3 days of pretreatment with progesterone (3 X 50 mg/kg b. w. i. p.) bile flow and TBA-excretion were diminished. Phenylbutazone (100 mg/kg b. w. i. p.) increased bile flow and TBA-excretion both after acute and subacute administration.
SDH activity in liver homogenates increases threetimes from one day before to one day after birth. The plateau till the 13th day of life is followed by a minimum on the 15th day of life, thereafter the increase leads to a maximum on the 120th day. The influence of phenylbutazone and barbital on body and liver weight as well as on hepatic SDH activity was investigated in different age groups. Both drugs were administered in three single daily doses, phenylbutazone additionally 31 days long. Hepatic SDH activity based on liver wet weight or liver protein did not change in any of the experimental groups. But as a consequence of increased liver body weight ratio (mostly non-significant), hepatic activity per gram body weight exhibited a tendency to higher values.
Explore the source record for details and available documents.