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Biomedical subjects

C Fleck

Publications and source records attributed to C Fleck.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1988

Relation between renal and hepatic excretion in drugs. VIII. Influence of triiodothyronine on maturation of phenol red excretion in rats.

Experiments were performed on 10-, 20-, and 55-day-old female rats. Administration of triiodothyronine (T3; 10 or 20 micrograms/100 g b.wt. for 3 days, once daily) was followed by a significant increase in renal phenol red excretion in 20-day-old and older rats. In 10-day-old rats there was no stimulatory effect of T3 on renal excretion of the dye. On the other hand, biliary excretion of phenol red was significantly diminished in all age groups. Surprisingly, in nephrectomized rats there was a significant increase in hepatic dye excretion in 20- and 55-day-old rats after T3. This increase in transport capacity via liver was connected with a distinct rise of bile flow. In experiments on tissue slices phenol red accumulation was investigated at different medium concentrations. In renal cortical slices there was no significant influence of T3 on specific accumulation of phenol red per 1 g organ wet weight, whereas aerobic accumulation of the dye seems to be diminished in liver tissue after T3 treatment. But in all age groups kidney weight increased significantly. Calculation of total accumulation (= specific accumulation x organ wet weight) resulted in a significantly enhanced renal transport capacity for phenol red in all age groups. In contrast, total hepatic accumulation was reduced independently of age.

Aging↗
PubMed1988

Relation between renal and hepatic excretion of drugs: VII. Hepatic and renal excretion of phenol red in thioacetamide-induced acute and chronic liver damage.

Acute and chronic liver damage was induced in rats by thioacetamide (TAA). Centrilobular liver cell damage associated with an accumulation of lipid droplets was produced by a single high dose (10 mg TAA/100 g b.m.). Liver fibrosis, micronodular and macronodular liver cirrhosis were induced by chronic TAA treatment (300 ml/l drinking water for 1.5, 3 or 6 months). Acute administration of TAA caused a significant decrease of hepatic phenol red excretion but no compensatory increase of its urinary excretion. In contrast, 24 h after bile duct ligation renal excretion of the dye increased by about 50%. After chronic exposure to TAA for three months hepatic phenol red excretion remained reduced and renal excretion raised significantly. This compensatory increase of urinary excreted phenol red amounts did not occur after 6 months of TAA treatment, probably as a result of additional nephrotoxicity of TAA. Two weeks after cessation of TAA exposure for 3 months, hepatic and renal phenol red excretion returned to normal. Bile flow per animal increased significantly after 3 months of TAA exposure. Apparently this is due to a reduced intrahepatic reabsorption of canalicular bile in TAA-damaged liver.

Animals↗
PubMed1988

Relation between renal and hepatic excretion of drugs: IX. Acceleration of phenol red excretion via kidney and liver in rats of different ages by dexamethasone treatment.

Experiments were performed on 10-, 20-, and 55-day-old female rats. After treatment with dexamethasone (60 or 80 micrograms/100 g b.wt. for 3 days, once daily) there is a significant increase in renal phenol red excretion only in 10-day-old rats. In contrast, the stimulatory effect of dexamethasone treatment on the hepatic excretion of this dye occurs exclusively in mature, 55-day-old rats. After repeated administration of this hormone in nephrectomized rats there is an increase of hepatic phenol red excretion, and maximal transport capacity increases from 6-8 to 12 mg/100g b.wt. X hour. In renal cortical slices there is no significant influence of dexamethasone on phenol red accumulation in vitro, whereas accumulation of the dye in liver tissue seems to be diminished. In rats of all groups kidney and liver weights increased significantly after dexamethasone treatment. Calculation of total accumulation capacity (= accumulation per 1 g X organ wet weight) also results in unchanged accumulation capacity in the kidney, but transported phenol red amounts in the liver are distinctly diminished. This is in contrast to the in vivo findings. Possible reasons are discussed.

Aging↗
PubMed1988

Relation between renal and hepatic excretion of drugs. XI. Excretion of sulfonamides with various physico-chemical properties of different ages--influence of nephrectomy or bile duct ligation.

The pharmacokinetics of a series of 6-sulfonamides, with gradually increasing molecular weights, were studied in anaesthetized rats after intravenous bolus injection. Immature (20-day-old) and adult (55-day-old) rats were compared. In both age groups renal excretion of all sulfonamides tested here dominates (about 5- to 10-fold). In 20-day-old rats renal and hepatic excretions are immature and reach about 50% (liver) or 30% (kidney) of adult values. Relation between renal and hepatic excretion of sulfonamides is strongly correlated to the lipophilicity of these substances. Hepatic excretion of sulfonamides seems to be correlated to their pKa-values. Concerning their excretion via urine it is necessary to correlate different steps of renal transport to physico-chemical properties in detail. A general correlation between renal excretion of sulfonamides and their chemical structure obviously does not exist. After bile duct ligation 24 h before clearance experiments no compensatory increase of renal sulfonamide excretion occurs. 24 h following bilateral nephrectomy hepatic excretion of sulfonamides is significantly enhanced; however, this phenomenon is related to physico-chemical properties of the sulfonamides. Age differences in compensation of one elimination pathway do not exist.

Aging↗
PubMed1988

Inhibition of kidney function after blockade of thromboxane synthetase by imidazole in anaesthetized rats.

Experiments on anaesthetized female Wistar rats have shown that imidazole reduces renal excretion of p-aminohippurate (PAH). This effect occurs only after administration of imidazole simultaneously with a volume load (2 ml/100 g b.wt.). Injection of imidazole immediately before a PAH bolus (100 mg/100 g b.wt. in 2 ml) is followed by reduced PAH excretion via urine for at least 1 hour. In contrast, if a PAH bolus is given 20 min or later after imidazole no effect of this drug on renal PAH transport is demonstrable. These findings indicate that imidazole can interfere effectively with thromboxane synthesis only if thromboxane production is activated by volume expansion. Interestingly, despite 40% reduction of renal PAH excretion in volumen loaded rats, PAH serum disappearance is identical in controls and imidazole treated rats. Thus differences in the volume of distribution for PAH after imidazole must be expected. Under our experimental conditions imidazole was without effect on renal electrolyte excretion.

Animals↗
PubMed1987

Aluminium induced damage of the lysosomes in the liver, spleen and kidneys of rats.

The influence of repeated aluminium (Al) administration (0.05 or 0.5 mg 100 g-1 b.w.t. i.p. 5 times weekly for 12 weeks) on the lysosomal enzymes N-acetyl-beta-D-glucosaminidase (beta-NAG) and beta-glucuronidase (beta-Gluc) in serum, liver, spleen and kidneys of adult female rats with intact kidneys, (NR), or following partial nephrectomy (5/6 NX) was investigated. After A1 loading, at the high dose only, the beta-NAG in serum and the free beta-NAG in liver, spleen and kidneys increased. Latent beta-NAG levels decreased in all three organs the effect being dose related. Following A1 loading no elevation in total enzyme activity was observed, with one exception. Depending on A1 doses the spleen of the non-operated animals, the liver of both groups of animals and the serum showed a decrease in beta-Gluc activity. No effect on beta-Gluc activity was observed in the spleen of 5/6 NX animals or in the kidneys of either group of animals. The results confirm that high doses of Al induce toxic effects and damage the lysosomes in the liver, the spleen and the kidneys. The results indicate that the extent of lysosomal damage correlates with dose and duration of Al loading. Repeated administration of Al also interferes selectively with enzyme synthesis.

Acetylglucosamine↗
PubMed1987

Relation between renal and hepatic excretion of drugs: III. Comparison of various methods reducing the renal or hepatic excretory capacity of rats.

In previous investigations bilateral nephrectomy (NX) and bile duct ligation (DL) were used to interrupt the renal or biliary excretion route, respectively. But competent doubt arose concerning the comparability of both interferences. In the case of DL the liver could influence the possible compensatory increase of renal excretion capacity; after removal of both kidneys such feedback on the liver is impossible. Therefore the corresponding operations were tested: bilateral ureter obstruction (UO) and so-called functional hepatectomy (fHX) caused by ligation of the porta hepatis. The time courses of a compensatory intensification of the excretory function of liver or kidney have been demonstrated. The following general conclusions can be drawn: fHX is characterized by some drawbacks because of its severe negative systemic effects. Thus DL should be preferred because the compensatory renal excretion capacity can be investigated without a significant reduction of the animal's vital forces. In contrast, NX seems to be the method of choice interrupting renal excretion. It is possible to remove both kidneys without a disturbance of other organ functions and the unpredictable effects of the hydronephrotic kidneys after UO on the whole organism are excluded. At least it is optimal to perform clearance studies approximately 24 h after both NX/UO or DL, because already at this time the phenomena of compensation have become maximal.

Animals↗
PubMed1987

Compensation of renal drug excretion after unilateral nephrectomy.

Twenty hours after unilateral nephrectomy (uNX) the PAH excretion of uninephrectomized rats reaches about 80% of the controls. Immediately after removal of one kidney the parenchyma loss can be compensated by an intensification of glomerular filtration. Thereafter the active tubular secretion capacity raises. 24 h after uNX, a significant increase of renal mass could be measured. The specific PAH accumulation capacity per 1 g renal cortical tissue increases significantly 96 h after uNX if the animals had been pretreated with cyclopenthiazide before the operation. Administration of azauracil or fluoruracil or neomycin causes a dose-dependent reduction of PAH elimination in sham operated as well as in uNX-rats. The effect of stimulation by cyclopenthiazide, also occurring after uNX could be reduced significantly by the inhibitors. The relative extent of compensation (80 +/- 10%) was not influenced by the inhibitors of protein synthesis. The compensation after uNX and the stimulation of renal tubular function are mediated by different mechanisms.

Adaptation, Physiological↗
PubMed1987

Relation between renal and hepatic excretion of drugs. IV. Influence of nephrectomy or bile duct ligation on the accumulation of phenol red in kidney and liver tissue of rats of different ages.

Based on in-vivo experiments investigating the relation between renal and hepatic excretion of phenol red in rats of different ages it was the aim of the present study to characterize the in-vitro accumulation of this dye in 10- and 55-day-old rats. Furthermore the influence of unilateral (uNX) or bilateral nephrectomy (NX) or bile duct ligation (DL) on renal and/or hepatic accumulation was characterized. The aerobic accumulation of phenol red is nearly twofold in kidney slices compared to that of liver tissue. In both organs and both age groups a self depression limit of phenol red accumulation can be measured. Under anaerobic incubation conditions in the liver nearly no accumulation of the dye occurs. However, in kidney slices the uptake under nitrogen atmosphere surpasses the aerobic accumulation. For this reason the accumulation in kidney slices is mainly a passive one caused by intracellular binding of the dye. There exist an influx carrier system as well as an efflux carrier in the kidney. The hepatic accumulation is first of all an active process. The accumulation capacity develops with increasing age. However, only quantitative differences occur and accumulation of young and adult animals does not differ qualitatively. 24 h after NX or DL and uNX phenol red accumulation is diminished in the liver or in kidney and liver, respectively. Transport capacity of liver tissue is more inhibited after these operations in adult animals than in 10-day-old-rats.

Animals↗
PubMed1987

Relation between renal and hepatic excretion of drugs. VI. Influence of pretreatment with phenol red on renal excretion and accumulation capacity of kidney or liver slices of immature and adult rats.

Pretreatment with phenol red causes a significant increase in renal excretion of p-amino-hippurate (PAH) in adult rats. In vitro experiments have shown that phenol red pretreatment significantly enhances the accumulation of PAH in renal tubular cells of adult rats. Thus the stimulation of active renal tubular PAH transport is at least in part responsible for its accelerated excretion via urine. A similar phenol red administration does not enhance the renal excretion of this dye, neither in adult nor in immature rats. In accordance with these in vivo findings the renal accumulation of phenol red is not increased after pretreatment with this dye. Remarkably the repeated administration of phenol red causes a distinct reduction of phenol red accumulation capacity in liver tissue. The rate of accumulation of both PAH and phenol red in renal cortical slices increases significantly during maturation; in liver tissue slices such an intensification does not occur. Under anaerobic conditions an active energy requiring uptake of phenol red does not take place and an accumulation by active transport of the dye can also be excluded. Therefore a passive uptake of phenol red and a binding of the dye in renal tubular cells could explain the distinct accumulation of phenol red in tissue slices from the kidney under nitrogen atmosphere. In 55-day-old rats the anaerobic phenol red accumulation in the liver is diminished after pretreatment with this dye.

Aging↗
PubMed1987

Relation between renal and hepatic excretion of drugs. V. Factors influencing accumulation of phenol red in kidney and liver tissues from rats of different ages.

Following bile duct ligation (DL) or bilateral nephrectomy (NX), phenol red accumulation in kidney or liver tissue, respectively, is reduced in rats of different ages. This is in contrast to in vivo experiments showing a compensatory increase of renal or hepatic excretion of phenol red in adult rats after DL or NX, respectively. The present study was performed to clarify this discrepancy. Three possible reasons were taken into consideration: 1. competition between accumulation of phenol red and bilirubin or bile acids; 2. influence of humoral factors occurring in serum of DL-rats on accumulation capacity; 3. changes of phenol red binding in homogenate of the kidney cortex or liver tissue after DL or NX. Ad 1. There exist inhibitory effects of bilirubin and cholic acid on phenol red accumulation. This inhibition is a competitive as well as a toxic one, apparently caused by a reduction of intracellular phenol red binding. Similar results have been obtained in in vivo experiments. During continuous infusion of bilirubin both renal and hepatic excretion of phenol red is significantly diminished. Ad 2. Incubation of tissue slices of control animals in serum of DL-rats does not indicate the existence of humoral factors reducing accumulation of phenol red after DL. Only in adult rats the plasma protein binding of phenol red is reduced after DL; in 10-day-old rats the binding capacity of the proteins for the dye is unchanged after DL. Ad 3. In young animals the phenol red binding on tissue homogenate is significantly reduced after DL or NX in kidney or liver; binding capacity of adult rats' tissue homogenate is unchanged after both operations. It can be concluded that renal and hepatic excretion capacity cannot be increased within a few hours after these blocking operations and obviously a functional reserve of the transport mechanisms does not exist.

Aging↗
PubMed1986

Renal effects of aluminium in uraemic rats and in rats with intact kidney function.

The effect on renal function following administration of aluminium (i.p., five times weekly (0.05 or 0.5 mg kg-1 body weight) for 12 weeks) to partially nephrectomized (5/6 NX) or intact female rats was examined. The observed loss of concentrating ability, characterized by increased urine volume and an increased sodium excretion, as well as increased renal excretion of p-aminohippurate (demonstrable after low-dose treatment with nephrotoxins) can be interpreted as an initiation of kidney function injury. No distinct differences in response were observed between partially nephrectomized and intact animals.

Aluminum↗
PubMed1986

Evidence for an intestinal lithium excretion in rats.

Renal, biliary, and faecal lithium excretion as well as intracellular lithium concentrations in different segments of the intestine were measured simultaneously in anaesthetized adult rats following sham operation, after ligation of the hilus of one or both kidneys, and after bilateral ligation of the renal hilus and additional bile duct ligation. Lithium was administered intravenously (300 mumol/100 g b.wt.) and thereafter lithium, sodium and potassium were measured up to 3 h in the different biological materials. The results give evidence that only one fifth of the lithium determined in faeces reached the small intestine via bile. Dependent on the type of restricted elimination, an increased lithium content was measured in faeces, which was distinctly higher in the colon than in the two small intestine segments. In contrast, no changes in biliary lithium excretion were observed. A slower decrease in the time course of serum lithium concentrations demonstrated that the loss of the other elimination routes cannot be compensated completely by the enhanced faecal lithium output. But lithium concentrations were found to be lower in serum than in the intestinal tissue segments and were highest in the segmental samples of faeces. On this basis an active transcellular transport step for lithium must be supposed beside the possibility of a paracellular transfer across the intestine. The lithium-induced changes of the sodium and potassium concentrations observed in the intestinal tissue and in the faeces support this interpretation.

Animals↗
PubMed1986

Relation between renal and hepatic excretion of drugs: I. Phenol red in comparison with p-aminohippurate and indocyanine green.

Phenol red is a suitable compound for the simultaneous assay of renal and hepatic excretion in the rat. Its elimination has been compared with those of p-aminohippurate (PAH) and indocyanine green (ICG) which are eliminated nearly exclusively via kidneys or liver, respectively. The interruption of one elimination route one day before the experiment, that means bile duct ligation (DL) in the case of ICG or bilateral nephrectomy (NX) in the case of PAH are followed by a slight increase in the elimination via the alternative pathway, but no effective compensation occurs. On the other hand, the renal excretion of phenol red is significantly increased after DL only following administration of high doses. This intensification is caused by an increase in the unbound amount of phenol red depending on the plasma concentration and reflects an enhanced glomerular filtration fraction. The biliary excretion increases significantly after NX, but only after infusion of low doses. The maximal biliary secretion capacity cannot be exceeded following NX, either. The competitive inhibition of phenol red excretion by probenecid supports the findings of NX or DL experiments. An influence of the three test substances on arterial blood pressure has been excluded. The most important factors influencing the switch over from one to the other elimination route seem to be at least in the case of phenol red the amount of unbound substance, the influence of the administered dose on the glomerular filtration, and disturbances in the volume of distribution, e.g. the possible reduction of hepatic uptake after DL.

Aminohippuric Acids↗
PubMed1986

Relation between renal and hepatic excretion of drugs. II. Age-dependence of phenol red excretion in comparison with those of p-aminohippurate and indocyanine green.

The excretory functions of kidney and liver do not develop simultaneously during the maturation of an individual. Therefore age related differences in the relation between renal and hepatic drug excretion could be expected. In this study the excretion of p-aminohippurate (PAH) and indocyanine green (ICG) as model substances for nearly exclusive excretion via kidney or liver, respectively, have been compared with that of phenol red eliminated both via kidneys and liver (3:1). Experiments were performed on rats between the 10th and 105th days of life. For PAH and ICG the typical age courses of renal or hepatic excretion have been confirmed. Both urinary and biliary phenol red excretion show an influence of age, however, renal elimination reaches adult values as early as at the 20th day of life. Furthermore the age relation concerning compensation of the loss of kidney or liver excretory functions has been studied. Neither after nephrectomy (NX) nor after bile duct ligation (DL) the PAH or ICG elimination via the alternative pathway, respectively, were quantitatively increased. Thus a compensation of the interruption of the main elimination route does not occur in all ages. In contrast, phenol red excretion into urine and bile increases distinctly after DL or NX. This increase becomes even significant after administration of suitable doses of phenol red saturating transport capacities of liver or kidney. The compensation is first of all caused by passive pharmacokinetic changes. Active compensatory mechanisms have not been proved.

Aging↗