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C Fleck

Publications and source records attributed to C Fleck.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1984

Methods in testing interrelationships between excretion of drugs via urine and bile.

The liver and kidney are largely responsible for inactivating and eliminating drugs and other chemicals. As the excretory capabilities of the two organs overlap, a damage of one system might be compensated by the other. Because of the specificity of both renal and hepatic elimination mechanisms such an alternative excretion route is not possible generally. Several interferences are possible to characterize the relation between hepatic and renal excretion of drugs and xenobiotics. Firstly, the simultaneous assay of excreted drug amounts in urine and bile can give some information concerning the main transport routes of this drug. Thereafter the total interruption of liver or kidney function elucidates the general possibility of alternative excretion routes. But it is important for clinical practice to distinguish between different localizations of organ damages. Today some experimental possibilities exist to exclude partial functions of both kidney and liver separately. Thus it can be clarified why a compound might be excreted via liver or kidney. Moreover it can be characterized whether or not a compensation for the loss of one main excretion organ is possible or not. Such investigations are of some practical importance. Dosing guidelines for drug therapy must be completed for cases of renal or hepatic failure. Moreover the developmental pattern of both elimination routes has consequences for drug use in paediatrics as well as geriatrics. Beside this point of view such investigations are necessary for the prediction of changes in the toxicity of drugs after renal or hepatic insufficiency.

Absorption↗
PubMed1984

Kidney function after unilateral nephrectomy.

Immediately after unilateral nephrectomy ( uNX ) some different mechanisms of compensatory adaptation begin to act followed by a restoration of sufficient kidney function in a short time period. Beside biochemical changes early compensatory hypertrophy of the remaining kidney occurs. Simultaneously, functional adaptations of renal blood flow, glomerular filtration and exertion of electrolyte and xenobiotics take place. With a suitable pretreatment it is principally possible to accelerate the regeneration phase. Thus the phase of reduced excretion capacity of tubularly secreted xenobiotics after removal of one kidney can be shortened or prevented.

Adaptation, Physiological↗
PubMed1983

Influence of inhibitors of protein synthesis on restitution of tubular transport capacity after unilateral nephrectomy.

One day after unilateral nephrectomy (uNX), excretion of p-aminohippurate (PAH) reaches 80% of control values in rats. A stimulation of tubular transport by repeated administration of xenobiotics shortened the phase of diminished PAH excretion capacity following. The relative extent of compensation (%) after uNX is not affected significantly by inhibitors of protein synthesis. These inhibitors influence the time course of compensation after uNX. Administration of azauracil, fluorouracil and neomycin, respectively, causes a dose dependent reduction of PAH excretion in nephrectomized and sham operated animals. This effect is also provable following pretreatment with cyclopenthiazide, which can stimulate the PAH elimination. A stimulated renal function after uNX can also be suppressed by high doses of inhibitors of protein synthesis. In contrast to this, small doses of these substances produce a stimulation of renal PAH excretion. The extent of this stimulation reached the same degree as after cyclopenthiazide pretreatment found in preliminary experiments. An additional treatment with cyclopenthiazide does not additionally increase PAH excretion. These results indicate that processes of compensatory growth as well as induction of renal tubular transport are caused by increased protein synthesis.

Animals↗
PubMed1983

[Dose- and age-dependence of the renal tubular transport of p-aminohippuric acid (PAH) in rats after injection of single doses].

The renal excretory capacity for tubularly eliminated foreign substances can be determined with certainty by measuring the excretion of p-aminohippuric acid (PAH). To make superfluous the laborious estimation of the maximum tubular transport capacity in the framework of screening programs, the authors established those doses of PAH the single application of which permits to assess the renal tubular transport capacity of rats of differing ages. Because of its selective renal excretion, it is possible to calculate for PAH a half-time value in urine (t1/2, urine) such as commonly indicated for the serum. Except for extremely high dosages (500 mg PAH/100 g body mass: intraperitoneally), the t1/2, urine value for PAH in adult rats is independent of the dose applied. The t1/2, urine value increases in rats 5 and 10 d of age with increasing PAH doses. In rats of all age-groups, the glomerularly filtered PAH proportion increases with increasing dosage (kinetics in decreasing blood level). In rats 5 and 10 d of age, the proportion of glomerularly filtered PAH in the total amount of excreted PAH is greater than in older rats.

Aging↗
PubMed1982

Failure of physostigmine in intoxications with tricyclic antidepressants in rats.

In experiments on rats there is a moderate antagonistic effect of physostigmine against intoxications with the tricyclic antidepressants (TAD) clomipramine, desipramine and imipramine, respectively. During the first hours after TAD intoxication the survival rate is higher in physostigmine treated rats. Especially after relatively low doses of TAD the lethality seems to be reduced by physostigmine treatment. However, at the end of the observation period (96 h) the lethality after TAD is equal with and without physostigmine treatment. The effectivity of physostigmine does not depend on the mode of administration: repeated administration and intravenous infusion are not more effective than a single injection of physostigmine. The influence of TAD on heart rate and respiratory rate was not abolished by physostigmine salicylate. Intoxications with high doses of physostigmine were antagonized by atropine; on the other hand there are no signs for an antagonistic effect of desipramine against physostigmine intoxication, that means their anticipated anticholinergic properties could not be proved.

Animals↗
PubMed1981

Urinary enzyme excretion as a indicator of nephrotoxicity in dependence on age.

It was tested whether or not the measurement of urinary enzyme excretion is suitable for detection of nephrotoxic effects in newborn and in old aged rats in the same way as in adult rats. In rats of different ages the renal excretion of lactate dehydrogenase (LDH), leucine aminopeptidase (LAP) and alkaline phosphatase (alP) was measured after administration of a single nephrotoxic dose of uranyl nitrate (0.6 mg/100 g b.wt.). In adult and old aged rats the three enzymes indicate the nephrotoxic effect reliably. In 15- and 20-day-old rats only the alkaline phosphatase seems to be an indicator for the nephrotoxicity of uranyl nitrate. There are differences in the time course of enzymuria in dependence on age.

Aging↗
PubMed1981

Stimulation of renal excretion of p-aminohippurate (PAH) after unilateral nephrectomy in adult and ageing rats.

Unilateral nephrectomy (UNX) is followed by a significant decrease of excreted amount of PAH in rats. In 105 and 240-day-old rats, we characterized the time course of restitution of the PAH transport process., Furthermore, we studied whether or not the regeneration of kidney function can be accelerated by repeated administration of cyclopenthiazide. After stimulation of tubular transport of PAH by repeated administration of cyclopenthiazide, the loss of one kidney after UNX can be compensated more rapidly as in nephrectomized rats without pretreatment. In 105-day-old rats the regeneration and the extent of stimulation are more marked than in 240-day-old rats.

Aging↗
PubMed1981

Renal blood flow after stimulation of p-aminohippurate transport.

Repeated administration of cyclopenthiazide enhances renal PAH excretion in rats. In the 1st hr after an acute PAH load the renal excretion of PAH is doubled compared with controls. Haemodynamic measurements show that this acute PAH load is related to an increase in renal blood flow, in particular to a distinct increase in blood flow in the renal cortex. This increase in renal blood flow and in intrarenal blood distribution is higher than in stimulated rats. The increase in renal excretion of PAH is stimulated rats is not connected with an increase in renal blood flow. After an acute PAH load an additional increase in renal blood flow in stimulated rats could not be observed as compared with non stimulated control rats.

Aminohippuric Acids↗