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Biomedical subjects

C Fleck

Publications and source records attributed to C Fleck.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1981

[Stimulation of the renal transport of foreign substances following unilateral nephrectomy].

During the phase of compensation of parenchyma loss two different mechanisms can be stated causing an improvement of renal tubular transport capacity. Besides an increase of tubular transport ratio in kidney slices from nephrectomized rats an increased mass of kidney tissue participated in the augmented transport capacity. 24 h after unilateral nephrectomy TmPAH is elevated from 0.40 +/- 0.10 to 0.61 +/- 0.13 mg/min x g kidney weight. The simultaneous increase in slice-to-medium ratio of renal cortical slices demonstrate the increase in specific transport capacity of regenerating kidney tissue. Furthermore the increase in kidney mass is the reason for an elevated transport capacity. Stimulation of renal PAH excretion by repeated pretreatment with cyclopenthiazide shortened the phase of compensation and raised the extent of tubular transport capacity following partial loss of kidney tissue. The specific accumulation of PAH in renal cortical slices from nephrectomized, cyclopenthiazide pretreated rats is distinctly elevated 96 h after unilateral nephrectomy from 19.4 +/- 2.7 to 24.3 +/- 0.6 micrograms/g kidney weight. Obviously there are different mechanisms for the increased PAH transport caused by stimulation and by regeneration after unilateral nephrectomy, because additional effects can be stated in regenerating rats by additional stimulation of renal tubular transport.

Aminohippuric Acids↗
PubMed1980

Stimulation of kidney function in rats injured by nephrotoxic agents.

After single administration of potassium dichromate or glycerol, renal PAH excretion was markedly reduced in adult, but not in newborn and infant rats. As already demonstrated in rats with intact kidney functions, repeated administration of PAH or cyclopenthiazide stimulates also renal PAH excretion in rats with acute renal failure. In detail, after PAH or cyclopenthiazide treatment of rats the duration of injury is shortened whereas the intensity of the nephrotoxic effects is not changed. However, the stimulation depends on the age of animals as well as on the nephrotoxic agent administered.

Aging↗
PubMed1979

Stimulation of kidney function in rats of different ages injured by nephrotoxic agents.

Intensity and duration of nephrotoxic effects can be characterized by measurement of renal p-aminohippurate (PAH) excretion. Single administration of potassium dichromate or glycerol is followed by a marked decrease of renal PAH excretion in dependence on the time after the administration as well as on the dosage used. Both agents are without effect in young rats with an immature tubular transport system for organic anions. As observed previously in rats with intact kidney function, renal PAH excretion can also be stimulated in rats with potassium dichromate or glycerol induced kidney damage. Stimulation of renal PAH excretion is possible in injured rats by repeated administrations of PAH and cyclopenthiazide, respectively. Exactly, the duration of injury is shortened whereas the intensity of the nephrotoxic effect is not changed. However, this effect depends on the age of rats as well as on the nephrotoxic agent administered.

Aging↗
PubMedDate not supplied

Ontogenetic aspects of thallium-induced nephrotoxicity in rats.

The effect of Tl2SO4 (Tl, 20 mg kg-1 body wt.) on renal function was investigated in 10- and 20-day-old rats. Nephrotoxic effects were evaluated by the determination of glomerular filtration rate, urinary volume, electrolyte and protein excretion, as well as by morphological investigations. In contrast to adult rats there were no morphological destructions in 10- and 20-day-old rats. Changes in renal function seemed to be less expressed in 10- and 20-day-old than in adult rats. The smaller nephrotoxicity in 10-day-old rats may be caused by lower Tl concentration in renal tissue, whereas in 20-day-old rats decreased nephrotoxicity cannot be explained in this way. The activity of Na+/K(+)-ATPase in rat renal tissues was found to be involved in the mechanisms of Tl enrichment in renal tissue, being an indirect determinant of Tl nephrotoxicity.

Animals↗
PubMedDate not supplied

Protective effects of methimazole against cisplatin-induced nephrotoxicity in rats.

In adult rats 6 mg kg-1 body wt. cisplatin given i.p. was nephrotoxic. Four days of i.p. treatment with 40 mg kg-1 body wt. methimazole, which started 1 day before CP, prevented increases in blood urea nitrogen and in the renal excretion of proteins. Furthermore, methimazole treatment reduced the oliguric effect of cisplatin and the depression of renal sodium excretion. However, it had no effect on the increased formation of lipid peroxides in cisplatin-damaged kidneys, although repeated treatment with methimazole enhanced the renal glutathione content. Methimazole acts as a radical scavenger, maintaining the glutathione pool in the kidney.

Animals↗
PubMedDate not supplied

Renal transport of endogenous amino acids. I. Comparison between immature and adult rats.

In the late neonatal period of male Wistar rats (10 days old) concentrations in plasma were higher for 5 of 24 amino acids compared to adult animals (2 months old): beta-alanine, tyrosine, glycine, histidine, and the dipeptide anserine. The plasma concentrations of tryptophan, valine and leucine were lower in young than in adult rats. The renal clearances of amino acids were lower in young rats, both in relation to 1 g b.w. and related to 1 g kidney weight. In the latter case the differences became more distinct because the relative kidney weight was higher in young than in adult animals (1.17 +/- 0.07 vs. 0.82 +/- 0.03 g/100 g b.w.) and significant age differences in renal water content did not exist. The apparently more effective tubular reabsorption capacity in young rats can be explained as follows: Because of the significantly lower GFR in 10-day-old rats compared with adults (0.46 +/- 0.03 vs. 1.10 +/- 0.09 ml/min/1 g kidney), the glomerularly filtered load of amino acids is generally lower in young rats (exceptions: tyrosine, glycine). Therefore, the amino acid transporting carrier systems are able to reabsorb the absolutely lower amounts of amino acids from the ultrafiltrate in immature animals. This hypothesis is supported if one relates the renal amino acid clearance to the clearance of inulin. In this way it is possible to show that there are absolutely no differences between both age groups indicating mature transport systems for endogenous amino acids as early as in 10-day-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗