Biomedical subjects

C Fleck

Publications and source records attributed to C Fleck.

At least 19 recordsLinked to original sources

PubMed1992

Liver function after bilateral nephrectomy.

Consequences of bilateral nephrectomy (NX) for liver functions and for hepatic excretion of various endogenous substances were characterized in rats 24 h after NX. Plasma concentrations of urea, creatinine, fibrinogen, and glutathione increased significantly after NX, whereas the concentrations of total protein, albumin, and lipids decreased. The hepatic excretion of urea, creatinine, phospholipids, cholesterol, and aldosterone significantly increased in uremia, and excretions of protein and glutathione diminished. Active biliary transport can be diminished after NX by the effects of uremic toxins on the liver cells or by the competition phenomena between endogenous substances, which are normally excreted in urine, at the hepatocellular level. Reduced glutathione content and increased lipid peroxidation in hepatocytes have been found. Changes in lipid and protein metabolism after NX can be proved.

Albumins↗

PubMed1992

Biliary amino acid excretion in rats before and after bilateral nephrectomy.

In previous studies it could be shown that after bilateral nephrectomy (NX) the excretory function of the liver is disturbed. To further clarify whether or not this "renohepatic syndrome" is caused by toxic effects of uremia or by competition phenomena between various uraemic toxins an additional aspect was investigated: the biliary excretion of endogenous amino acids. Furthermore, previously it could be shown that renal and hepatic excretory functions overlap. Therefore, the renal excretion of effectively biliary eliminated amino acids (glutamic acid, alanine, tyrosine, isoleucine) is very low and vice versa. That means, that the renal excretion of amino acids with low hepatic elimination (tryptophan, citrulline, lysine, taurine) dominates. The hepatic excretion of amino acids is hardly altered after NX. Remarkably, the removal of both kidneys is followed by a distinct reduction in amino acid plasma concentrations, especially if these concentrations are relatively high in the controls. Interestingly, there is no correlation between plasma concentrations and biliary excretion of amino acids. But the calculation of the bile to plasma concentration ratios of amino acids makes it possible to differentiate three groups of amino acids: Amino acids excreted actively into bile (ratio > or = 1), amino acids with ratios below 1, indicating effective retention, and amino acids with ratios of about 1, whose hepatic handling is passive. After NX these ratios tended to approach 1; low ratios increased and high ratios decreased. That means, active processes involved in excretion or retention are obviously disturbed. These changes could indicate uraemic liver damage as proved regarding influence of NX on hepatic excretion of other endogenous substances and xenobiotics.

Amino Acids↗

PubMed1992

[The occurrence of aluminum-containing lysosomes in the kidney of experimentally treated rats].

Aluminium was detected by electron spectroscopic imaging and electron energy loss spectra in the lysosomes of all cell types of the nephron in rats treated with aluminium chloride after 5/6 nephrectomy. The lysosomes of kidney cells of untreated rats did not demonstrate any detectable amounts of aluminium. Electron energy loss spectra showed the regular occurrence of iron (and also other elements) in the lysosomes of both groups of rats.

Aluminum↗

PubMed1991

Influence of vasoactive substances on uremic bleeding in rats.

Bleeding time is prolonged following resection of kidney tissue as well as after ureteral occlusion. Bilateral nephrectomy raises bleeding time from 17 to 67 min, and blood loss can be increased from 2 to 12 microliters/min. Plasmatic coagulation factors remain unchanged in uremic rats. There is no influence of various surgical interventions producing uremia on function of thrombocytes. In rats with intact kidney function and following bilateral nephrectomy a diminution of bleeding time is demonstrable after administration of histamine or captopril. Shortening of bleeding time by the antifibrinolytic substance p-aminomethylbenzoic acid seems to indicate an increased fibrinolytic activity in uremic rats.

4-Aminobenzoic Acid↗

PubMed1991

Relation between renal and hepatic excretion of drugs. XIV. Elimination of ioglycamic acid after nephrectomy, bile duct ligation, and after treatment with hormones or xenobiotics in young and adult rats.

Ioglycamic acid (IGA) is effectively eliminated in young and adult rats via urine and bile. After administration of low doses hepatic excretion dominates whereas following high supply renal elimination surpasses biliary excretion. Hepatic transport of IGA is active, indicated by the occurrence of a transport maximum in vivo and by a distinct accumulation of this drug within liver slices in vitro. Renal removal of IGA is preferentially caused by glomerular filtration. A tubular reabsorption obviously does not occur because forced diuresis (mannitol, furosemide) does not increase renal excretion of this substance. As calculated from our clearance data and as a result of accumulation experiments in vitro on renal cortical slices the active tubular secretion of this organic anion can be excluded. In principle there are no qualitative changes in IGA elimination between the 20th and 55th day of life, but active hepatic transport of the drug is significantly lower in young, immature rats. After bile duct ligation, renal excretion of IGA increases distinctly in both age groups, whereas in adult rats bilateral nephrectomy (NX) is followed by a significant decrease in its hepatic excretion in dependence on time after kidney removal. In young rats NX is without consequences on hepatic excretion of IGA. It is possible to stimulate renal and/or hepatic excretion of IGA by repeated administration of T3, dexamethasone, or phenobarbital. The effect of stimulation is different in kidney and liver and depends on age, too.

Animals↗

PubMed1991

Ontogenetic changes in hepatic glutathione system (synthesis, catabolism, export) of male Uje:WIST rats.

The age-courses of concentrations of reduced (GSH) and oxidized (GSSG) glutathione, of GSH synthesizing enzyme activities, of glutathione S-transferase (GST), of GSSG-reductase (GR) and of biliary GSH and GSSG export were measured in livers from male Uje:WIST rats. Additionally, the age-courses of plasma GSH and GSSG concentrations were investigated. The hepatic level of GSH showed a biphasic pattern with a first maximum immediately after birth and a small second peak at the 50th day of life. The GSSG level increased continuously up to day 60 of life. The cytosolic GSH synthesizing enzyme activities showed diverse developmental patterns indicating different regulation principles. The hepatic activity of GR was relatively constant in the different age groups after birth. The GST activity (with o-dinitrobenzene as substrate) was relatively low at birth (about 30% of the maximum measured at day 60 of life). The maximum of GSH plasma level was found at birth. With increasing age a significant decrease in this level was observed. The excretion rate of total GSH (GSH + 2 GSSG) in bile was found to increase about 9-fold between 15 and 105 days of age. The results indicate that changes of hepatic GSH concentration with age are dependent on numerous factors. The balance between synthesis, catabolism and export is important for the maintenance of this level.

Aging↗

PubMed1991

Relation between renal and hepatic excretion of drugs: XV. Organ distribution and transport of the new antiarrhythmic drug Bonnecor in kidney and liver of rats.

Following administration of various doses of 14C-labeled Bonnecor (0.15 to 0.6 mg/100 g b.wt. i.v.) renal excretion of 14C-radioactivity dominates and the total rate of excretion both via kidney and liver reaches 60% during 6 h clearance experiment, independent of the administered dose. Otherwise nearly the same concentration of 14C-radioactivity can be measured in kidney and liver tissue. An alpha- und beta-slope of disappearance from the tissue seems to exist. At different times after administration of Bonnecor (0 to 15 h) the concentrations in kidney and liver tissue are distinctly higher compared with plasma concentrations. In vitro experiments on tissue slices confirm a nearly identical degree of accumulation of 14C-radioactivity in liver and kidney. In renal cortical slices the high degree of accumulation depends on active tubular transport processes. Comparing accumulation in liver slices under aerobic and anaerobic conditions a preferential passive uptake of Bonnecor can be demonstrated. Efflux kinetics in slices from liver and kidney cortex is in accordance with this interpretation.

Animals↗

PubMed1991

[Electron microscopic evidence of aluminum in lysosomes of kidney cells by electron energy loss spectroscopy].

Aluminium effects have increasing attention in long term dialysis of kidney patients and in a number of cerebral diseases. At present, however, there are still many open points concerning its localization and actions in the cell. If using electron spectroscopic imaging (ESI), aluminium could be directly demonstrated in the lysosomes of the kidney cells of uraemic rats experimentally loaded with aluminium. These findings were corroborated by means of electron energy loss spectroscopy (EELS).

Aluminum↗

PubMed1990

[Possibilities for increasing the elimination rate of Bonnecor].

Bonnecor is excreted in rats both via urine (3/4) and bile (1/4). It was the aim of this study to find out suitable methods for detoxication of a poisoning with this antiarrhytmic drug. In vivo methods intended to enhance the renal excretion of Bonnecor (forced diuresis, changes in urinary pH-values, peritoneal dialysis) are not qualified for therapeutically relevant increase of Bonnecor elimination. Relating to this Bonnecor is quite comparable with other antiarrhythmic drugs or dibenzazepine derivatives. The hemoperfusion can be recommended for the therapy of a Bonnecor overdosage as a propping up of symptomatic methods of intensive care, which are precendentally indicated. Therefore the therapy of a Bonnecor poisoning seems to be more promising compared to intoxications with other antiarrhythmics. Among the adsorbents tested, the resin Wofatit UH91 is most suitable to remove Bonnecor from the organism. If hemoperfusion equipments are not available, hemodialysis can also be used for acceleration of Bonnecor elimination, although its effectivity is only one third of that of hemoperfusion.

Animals↗

PubMed1990

Influence of xenobiotics on bile flow and bile composition in rats--methodological approach.

Optimal procedures for the investigation of bile flow and excretion of bile constituents are described, and data are given regarding sex and age dependency, use of narcotic drugs and replacement of water loss in Wistar rats. A combination of ketamine and xylazine can be recommended for anaesthesia. In long time studies saline infusion keeps bile and urine production constant over a period of 6 h. Bile flow and biliary excretion of bile acids and electrolytes are immature at birth and reach a maximum between the 20th and 60th day of life. The biliary excretion of cholesterol decreases with age. The concentrations of bile constituents such as lipids, glutathione, protein, uric acid, urea, osmotically active substances, and steroid hormones are given for adult rats. Bilateral nephrectomy decreases bile flow in mature rats only.

Aging↗

PubMed1990

Age dependent differences in stimulation and compensation of renal and biliary transport processes. Correlation to the physicochemical properties of the exerted substances.

The relation between renal and biliary excretion of drugs was investigated in dependence on physicochemical factors, on age, and on repeated administration of hormones and xenobiotics for stimulation. Furthermore, the relation between molecular parameters of drugs and the degree of compensation of drug elimination after blockade of one excretion pathway (nephrectomy--NX, bile duct ligation--DL) was characterized. Experiments were performed on female 20-day and 55-day-old rats to demonstrate changes in the relationship between kidney and liver for drug elimination during ontogenesis. Finally it was tried to correlate the effect of a stimulation of elimination capacity of kidney and liver after repeated administration of hormones or xenobiotics and the physicochemical features of clearance substances tested. For estimation of physicochemical differences of the model substances a so called "rank coefficient" R (0-100) was used. It was calculated from molecular weight, lipophilicity, degree of ionization at pH 7.4, and protein binding rate. Compounds with low ranks (low values of molecular weight, lipophilicity, and protein binding, nearly completely ionic at pH 7.4) are eliminated first of all via urine. High ranks are typical of drugs preferentially eliminated into bile. Intermediate ranks (40-60) have been obtained for substances eliminated effectively both via kidney and liver. For these compounds only, a distinct compensation via the intact elimination route can be expected after blocking operations. Qualitative age differences could not be found. But there were differences concerning relation between acceleration of transport capacity of kidney and liver during postnatal maturation and physicochemical properties of the respective test substance.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1990

Factors determining the relationship between renal and hepatic excretion of xenobiotics.

Relation between kidney and liver in the excretion of drugs depends on the physicochemical properties of each substance tested. The calculations of this relationship are based on a so-called rank coefficient (0-100) calculated from molecular weight, lipophilicity, degree of dissociation under physiological conditions, and protein binding rate. The results of the correlation between one of these physicochemical values and drug elimination were stochastically. Experiments were performed with 9 test substances which were distinctly different concerning their physicochemical features. Substances with a rank coefficient less than 20 (low molecular weight, low lipophilicity, preferentially ionic at pH 7.4) are eliminated effectively via the kidney. Compounds having an intermediate rank coefficient (40-60) were quantitatively excreted into urine as well. For drugs with high ranks greater than 60 (high values of molecular weight, protein binding, and lipophilicity, almost exclusively nonionic), renal excretion can be neglected. Quite inverse relations between ranks and hepatic excretion have been found: low ranks indicate an ineffective secretion of the respective drug into bile. With increasing ranks (40-60), biliary excretion increases and reaches a maximum (approximately 40% of supply). This maximum is caused by limited hepatic blood flow and by the capacity of hepatic uptake carriers. Blockade of one elimination pathway (bilateral nephrectomy or bile duct ligation) is followed by a sufficient compensation of drug excretion via the alternative elimination route only, if the test substance belongs to the intermediate group (ranks between 40 and 60). For substances with high or low ranks a compensation of drug excretion can be excluded.

Animals↗

PubMed1990

[The effect of propranolol (Obsidan) as well as propranolol and fenoterol (Partusisten) on the motility of the smooth uterus musculature in vitro].

Propranolol (1; Obsidan) relaxes in vitro stripes of smooth muscles of non-pregnant rat's uterus in a concentration dependent manner. In contrast, on uterine muscle stripes of pregnant rats 1 causes small contractions. In an combination of 1 and fenoterol (2; Partusisten) (20:1) 1 prevents the relaxing effect of 2, reported to be an inhibitor of uterine muscle activity. This antagonism is most distinct on stripes of pregnant rat's uterus.

Animals↗

PubMed1989

Relation between renal and hepatic excretion of drugs: XIII. Pharmacokinetics of new antiarrhythmic drug Bonnecor in rats with normal and impaired excretory functions.

The clearance of 14C-Bonnecor, a weak organic cation, was measured in anaesthetized rats during 6 h after administration. The drug and its labelled metabolites are excreted both via kidney and liver. The renal excretion dominates especially following high doses. After bile duct ligation the renal excretion of Bonnecor increases significantly whereas in nephrectomized rats the biliary excretion of this substance is distinctly reduced. Plasma protein binding ratios amount to 60-70%. Renal removal of Bonnecor and the formed metabolites is in part a result of glomerular filtration. Increased urinary excretion of 14C-Bonnecor-activity under conditions of forced diuresis indicates the involvement of tubular reabsorption in renal handling of the drug and its metabolites. These in vivo results could be confirmed in experiments on renal cortical slices indicating a distinct tubular transport of the drug and its metabolites. In the kidney the aerobic accumulation of Bonnecor is very effective. Surprisingly, under anaerobic incubation conditions, uptake of Bonnecor into renal tissue remains relatively high indicating a distinct binding of Bonnecor within the tubular cells. In the liver the accumulation of Bonnecor is lower compared to the kidney. Furthermore, enterohepatic circulation of Bonnecor and its metabolites was checked. In animals with intact biliary tract, renal removal of 14C-Bonnecor-activity from the organism is significantly higher than in rats with bile duct cannulation. Reinfusion of bile increased renal excretion of 14C-Bonnecor-activity additionally. Both results indicate an effective intestinal reabsorption and enterohepatic circulation of this drug.

Animals↗

PubMed1989

[Determination of the biliary excretion of reduced and oxidized glutathione].

An enzymatic method is presented for the detection of biliary excretion of reduced (GSH) and oxidized (GSSG) glutathione. The biliary excretion of GSH is 65.63 +/- 7.23 nmoles/kg b.w. x min and of GSSG 5.90 +/- 0.64 nmoles/kg b.w. x min in 55 day-old female rats, respectively. The recovery is 97.39 +/- 0.40% for GSH and 91.05 +/- 2.30% for GSSG. Cysteine which can be detected in bile, does not influence the accuracy of the results.

Animals↗

PubMed1989

Relation between renal and hepatic excretion of drugs. XII. Influence of dexamethasone, triiodothyronine, or phenobarbital on the elimination of sulfonamides in rats of different ages.

Relation between renal and hepatic excretion of sulfonamides depends on their physicochemical properties. So does the effect of treatment with triiodothyronine (T3), dexamethasone, or phenobarbital (PB) on elimination of sulfonamides. After repeated administration of T3, dexamethasone, or PB an intensification of biliary sulfaclomide excretion occurs whereas hepatic transport of sulfisomidine or sulfameracine is not affected. After T3 treatment, bile flow of adult rats with intact kidneys increases by 60%. This increase is connected with enhanced sodium excretion into bile. Renal excretion of the three sulfonamides investigated here seems not to be influenced by different kinds of treatment. However, if the tubular reabsorption within the kidney is diminished by forced diuresis renal sulfaclomide excretion is enhanced after treatment with T3, dexamethasone, or PB. Surprisingly, under these conditions (mannitol diuresis), sulfaclomide excretion via bile reaches only control values and stimulatory effects of all kinds of treatment are suppressed both in young and adult animals with the exception of dexamethasone in adult rats. In young rats treated with T3 or PB there is no additional compensatory increase in sulfaclomide excretion after nephrectomy whereas in adult rats sulfaclomide elimination via bile is significant diminished.

Animals↗

PubMed1989

[The effect of chronic aluminum loading on lysosomal enzymes in serum and organ homogenates. Methodologic aspects].

The influence of aluminium administration both on the lysosomes and on the activity of DNA-dependent enzymes in rats with intact kidney function or following partial nephrectomy was investigated. The elevation in free N-acetyl-beta-D-glucosaminidase in connection with a decrease of latent beta-NAG-level in liver, spleen and kidneys may be supposed a dose dependent aluminium damage of the lysosomes. Moreover, the decrease of free and total beta-glucuronidase in the liver and spleen could be caused by a selective inhibition of synthesis of this enzyme.

Acetylglucosamine↗

PubMed1988

Relation between renal and hepatic excretion of drugs: X. Excretion of nalorphine in young and adult rats pretreated with hormones or xenobiotics.

Different processes are involved in renal and hepatic excretion of organic anions and cations. In contrast to our knowledge of anion excretion, information about cation transport in kidney and liver is relatively scarce. In this study, the elimination of nalorphine was investigated to characterize the relation between renal and hepatic excretion of organic cations. Nalorphine is excreted effectively both via kidney and liver. However, its hepatic excretion dominates in adult rats. In young, 20-day-old animals biliary nalorphine elimination is immature and the excreted amounts are significantly lower. Renal excretion of nalorphine is quite similar in rats of both ages. After bile duct ligation renal excretion of nalorphine increases significantly in adult rats whereas it remains unchanged in young ones. Remarkably, after bilateral nephrectomy hepatic elimination of nalorphine is even diminished in both age groups. In further experiments renal excretion of nalorphine could be stimulated in adult rats after repeated administration of trometamol, triiodothyronine, or dexamethasone; these treatments had no consequences on biliary secretion of nalorphine.

Aging↗