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Biomedical subjects

D Maruhn

Publications and source records attributed to D Maruhn.

At least 19 recordsLinked to original sources
PubMed1999

Time course of chronic oral cadmium nephrotoxicity in Wistar rats: excretion of urinary enzymes.

Twelve male and female Wistar rats each received cadmium (as CdCl2) in their diet at concentrations of 0, 10, 50, and 250 ppm for 72 weeks. After 1, 4, 8, 13, 18, 26, 32, 45, 57, and 68 weeks a total of 8 enzymes from different cellular compartments of the nephron were measured. At the end of the study period, the kidneys were examined histopathologically. Concentrations up to and including 50 ppm did not induce any adverse effect. At 250 ppm, growth of male and female animals was markedly retarded. Significantly increased activities of the cytosolic phosphohexose isomerase were excreted by males and females receiving 250 ppm at all timepoints from week 13. The values of the mitochondrial glutamate dehydrogenase were mostly elevated from week 1 to 57, however, due to a wide scatter range, were only occasionally significantly different from control values. The brush border enzymes (gamma-glutamyl transferase, alkaline phosphatase and leucine arylamidase) were not changed in a relevant manner in female rats, while in 250 ppm males the excreted activity of ALP and LAP from week 1 to week 18, and that of GGT during the entire study period were significantly lower than the control values. Excretion of the lysosomal enzymes aryl sulfatase A, beta-galactosidase, and beta-N-acetyl-D-glucosaminidase was at no time influenced in a noteworthy manner. Histopathology after 72 weeks revealed chronic but also acute degenerative changes in the kidneys of 250 ppm males and females. A comparison of published data on persons having undergone high cadmium exposure with the results presented here shows remarkable differences.

Administration, Oral↗
PubMed1991

Excretion of urinary enzymes in female Sprague-Dawley rats in relation to cellular compartment, creatinine excretion and diuresis.

One hundred and one young-adult female Sprague-Dawley rats were acclimatized to metabolic cages for 2 days. After that time 24-hour urine was collected at a constant cooling temperature of 0-4 degrees C. After gel filtration the enzyme activities were determined, and the resulting values were used to calculate 24-hour excretions. The following reference ranges (2.5 and 97.5 percentiles) were determined (in mU/24 h): lactate dehydrogenase 43-181; phosphohexoseisomerase 45-1445; glutathione-S-transferase 1-299; alkaline phosphatase 27-1239; leucine arylamidase 72-377; gamma-glutamyltransferase 1334-9188; arylsulphatase A 59-309; beta-galactosidase 76-305; beta-glucuronidase 20-2756; beta-N-acetyl-D-glucosaminidase 66-491; glutamate dehydrogenase 7-711. There was a significant (though not very high) correlation with diuresis for the lysosomal enzymes beta-N-acetyl-D-glucosaminidase, arylsulphatase A and beta-galactosidase, and for glutamate dehydrogenase, lactate dehydrogenase, phosphohexoseisomerase and alkaline phosphatase. The relation to creatinine excretion was markedly close for the lysosomal enzymes beta-N-acetyl-D-glucosaminidase, arylsulphatase A and beta-galactosidase (r = 0.71-0.83), as well as for alkaline phosphatase, leucine arylamidase and gamma-glutamyltransferase. There was a relatively high correlation between the excretion of beta-N-acetyl-D-glucosaminidase, arylsulphatase A and beta-galactosidase among themselves (r = 0.63-0.81) as well as between leucine arylamidase and gamma-glutamyltransferase (r = 0.75).

Animals↗
PubMed1990

Determination of urinary glutathione S-transferase and lactate dehydrogenase for differentiation between proximal and distal nephron damage.

Cytosolic glutathione S-transferase (GST) activity is confined to the proximal convoluted and straight tubules. Damage to these parts of the nephron should result in leakage of GST into the urinary space. Lactate dehydrogenase (LDH), in contrast, is more generally distributed along the nephron. Measurement of both enzyme activities could therefore be expected to discriminate between different localizations of nephrotoxicity. To test this hypothesis, we determined both enzyme activities in 24 h urine samples from 10-12 female Sprague-Dawley rats, each treated with single i.p. injections of puromycin aminonucleoside (PAN, 130 mg/kg), Na2 CrO4 10, 20, 30 mg/kg), mercuric chloride (HgCl2, 0.5, 0.75, 1.0 mg/kg), folic acid (125, 350, 375 mg/kg), ethyleneimine (0.5, 2.0, 5.0 microliters/kg). Bovine serum albumin (BSA) was injected by the same method, twice daily on 3 consecutive days (2.5, 7.14 g/kg). The results obtained indicate a characteristic dose- and time-dependent pattern of excreted enzyme activities for each of the tested compounds. In both models with primarily glomerular damage, proximal tubular parts were also affected, as could be demonstrated by increased urinary GST and histopathological changes. Damage, mainly to the S1/S2 segment by 20 or 30 mg Na2 CrO4/kg, resulted in moderate to marked increases in LDH excretion, while GST was only moderately elevated at 30 mg/kg. Extreme increases in GST and LDH output were measured after predominant S3 segment damage after 0.75 and 1.0 mg HgCl2/kg. The distally active compounds, folic acid and ethyleneimine, did not increase GST excretion at lower doses. At the high doses, a small rise in GST excretion indicated some, probably secondary, proximal tubular involvement, which correlated with the histopathological findings in these groups.

Animals↗
PubMed1988

The effect of antipyrine and rifampicin on the excretion of renal enzymes in human urine.

Two well-known drugs that induce the liver microsomal enzyme system in man were administered to 3 different groups of healthy male volunteers. Antipyrine 1200 mg and rifampicin in two different doses of 600 mg or 1200 mg daily were given orally to each group over a period of seven days. The extent of liver microsomal enzyme induction was assessed by estimating antipyrine elimination, serum gamma-glutamyl-transferase (GGT) activity and the urinary excretion rate of 6-beta-hydroxycortisol. In addition, possible effects on renal enzymes were monitored by measuring gamma-glutamyltransferase (GGT) and beta-glucuronidase (GRS) urinary excretion rates before and after drug administration. The possibility of a direct toxic effect on the renal tubular epithelium following drug administration was assessed by the measurement of urinary beta-N-acetylglucosaminidase (AGS) activity, total protein and glucose. Antipyrine plasma clearance and 6-beta-OHF excretion rates increased significantly in the groups treated with antipyrine or rifampicin, while serum GGT activities were enhanced only following antipyrine. Antipyrine administration increased urinary GGT excretion both immediately and one week after cessation of drug administration, but no changes were found following the administration of rifampicin. GRS, AGS, total protein and glucose excretion in urine remained unchanged during and after the administration of each individual drug. Based on these findings, the increased urinary GGT excretion observed following antipyrine treatment may be due to an inducing effect on the renal tubular cells, as no evidence for a toxic renal damage was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Recommendation for the measurement of "alanine aminopeptidase" in urine.

A method is recommended for the measurement of the catalytic concentration of alanine aminopeptidase in the urine of man, rat, and dog, using L-alanine-4-nitroanilide as substrate. In currently used methods, substrate concentrations between 1.7 and 2.0 mmol/l are used. Kinetic experiments show, however, that the reaction is inhibited by substrate concentrations exceeding 0.8 (man), 0.3 (rat) and 0.5 mmol/l (dog); these concentrations lie in the range of the Km values. Assay conditions were therefore chosen to give the lowest possible Km. The Km value depends on the type of buffer, and it increases with pH and temperature. The recommended assay conditions are: triethanolamine buffer 70 mmol/l, pH 7.6; L-alanine-4-nitroanilide concentrations depending on the species; incubation temperature 25 degrees C.

Aminopeptidases↗
PubMed1986

A stable liquid control material for urinary enzyme assays.

A stable liquid control material for urinary enzyme assays was prepared by addition of ethylene glycol (30% v/v) or glycerol (30% v/v) to centrifuged urine, and pH adjustment to 7.0. Tested for 375 days, the material exhibited stable beta-N-acetylglucosaminidase, alanine aminopeptidase, gamma-glutamyltransferase and lactate dehydrogenase activities, at both 4 and -20 degrees C. The material further has been successfully evaluated in an external quality control program.

Enzyme Stability↗
PubMed1986

Urinary enzyme excretion after a single dose of phenacetin and paracetamol (acetaminophen) during antidiuresis and during water diuresis.

2 g phenacetin or paracetamol in a single oral dose were administered to five healthy persons under the conditions of antidiuresis and subsequent water diuresis. Excretion of the brush border enzyme GGT, the cytoplasm enzyme LDH, and the lysosomal enzymes, NAG and GAL, was analysed before, during and after ingestion of the analgesics. Increased excretion of LDH and GGT indicated a similar moderate damage of the tubular epithelia after phenacetin and paracetamol. The state of diuresis appeared to have no influence.

Acetaminophen↗
PubMed1986

Pharmacokinetics of ciprofloxacin. 2nd communication: distribution to and elimination from tissues and organs following single or repeated administration of [14C]ciprofloxacin in albino rats.

1-Cyclopropyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-[U-14C]piperazinyl)-3-quinoline carboxylic acid (ciprofloxacin, Bay o 9867; designated tradename: Ciprobay) was administered to male and to pregnant albino rats with single intravenous or oral doses of 5 or 10 mg/kg body weight and with repeated oral doses of 5 mg/kg (7 consecutive daily administrations to male rats). Following a single intravenous administration the [14C]ciprofloxacin related radioactivity was distributed rapidly and differentiated to the body. Compared to plasma high concentrations were determined in kidney, liver, skeleton muscle, pancreas, testes and cartilage, low concentrations occurred in brain and adipose tissue. In some selected tissues radioactivity was largely due to unchanged [14C]ciprofloxacin (57% to 100%). A good penetration of total radioactivity into tissues and organs with a similar distribution pattern as detected after intravenous dosing also occurred after a single oral administration. Highest concentrations were determined 1 h after dosing. Compared to plasma most tissues and organs showed higher concentrations and higher AUC-values. For brain and eye low values were determined. Compared to plasma a longer mean residence time of radioactivity was calculated for brain, eye, eye-wall, testes and blood cells. 6 d after single administration the radioactive residues in the body exclusive gastrointestinal tract amounted to less than 0.1% of the dose. Following a seven-day treatment the distribution pattern of total radioactivity in the body did not differ essentially from that after single dosing. Compared to single dosing AUC-values higher by the factor 2 to 4 were calculated after repeated administration for plasma and most of the tissues and organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1986

Pharmacokinetics of ciprofloxacin. 1st communication: absorption, concentrations in plasma, metabolism and excretion after a single administration of [14C]ciprofloxacin in albino rats and rhesus monkeys.

The absorption, disposition, metabolism and excretion of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-[U-14C]piperazinyl)-3- quinoline carboxylic acid (ciprofloxacin, Bay o 9867; designated tradename: Ciprobay) were studied following a single intraduodenal (rat), oral and intravenous (rat, monkey) administration, respectively, in the dose range 5 to 30 mg/kg body weight. Ciprofloxacin was absorbed partially (30 to 40%) in both species. Peak plasma concentrations of radioactivity were measured approximately 1 h (rat) or 2 h (monkey) after oral dosing. Terminal half-lives ranging from 26 to 44 h were determined for the elimination of radioactivity from the plasma (observation time up to 48 h after dosing). Nearly identical concentrations of the unchanged drug and total radioactivity were found during the first 7 or 8 h for the monkey after intravenous injection and for the rat also after oral administration, respectively. After reaching maximum concentration of 0.25 microgram/ml after administration of 5 mg/kg to rats and 0.88 microgram/ml after dosing with 30 mg/kg to a rhesus monkey, the unchanged drug was eliminated from plasma corresponding to half-lives ranging from 3 h (rat) and 4.4 h (monkey). The radioactivity was rapidly and completely excreted in both species. After intravenous administration about 51% (rat) and 61% (monkey), respectively, was excreted via the kidney. After oral dosing renal excretion amounted to 6-14% (rat) and 30% (monkey), respectively. Maximum residues in the body (exclusive gastrointestinal tract) of 1% of dose occurred in both species. In urine and feces of rats predominantly the unchanged drug and a conjugate were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1985

Pharmacokinetics of nimodipine. I. Communication: absorption, concentration in plasma and excretion after single administration of [14C]nimodipine in rat, dog and monkey.

Studies on absorption, plasma concentrations and excretion with (+/-)isopropyl-2-methoxyethyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl) -3,5-pyridinedicarboxylate (nimodipine, Bay e 9736, Nimotop) have been conducted in rat, dog and monkey using the carbon-14-labelled substance and a wide range of doses (0.05-10 mg/kg) administered via different routes (intravenous, oral, intraduodenal). Nimodipine was well absorbed in all species. Peak plasma concentrations of radioactivity were determined 28-40 min (male rat), 60 min (female rat), about 3 h (dog) and 7 h (monkey) after administration. Dependent on the observation period (24-216 h) terminal half-lives for the elimination of radioactivity from plasma ranging between 4.6 h (female rat) and 157 h (dog) were observed. Comparing the AUC, the concentration of unchanged [14C]nimodipine in plasma represented only a small (maximally 37% in dogs after i.v. dose) to negligible (about 1%, monkey after oral dosing) part of the total radioactivity. Excretion of radioactivity via feces and urine was rapid in all species after both oral and intravenous dosing. Fecal (biliary) excretion was the major excretory route in rat and dog. The monkeys excreted about 40 to 50% via the urine. Residues in the body never exceeded 1.5% of the dose. [14C]nimodipine and/or its radiolabelled metabolites were secreted in milk of orally dosed lactating rats. Binding of [14C]nimodipine to plasma proteins of rat and dog was about 97%.

Animals↗
PubMed1985

Pharmacokinetics of Nimodipine. II. Communication: distribution, elimination and placental transfer in rats following single and multiple doses of [14C]nimodipine.

(+/-)Isopropyl-2-methoxyethyl-1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl)-3,5-pyridinedicarboxylate (nimodipine, Bay e 9736, Nimotop) is a calcium antagonist from the 1,4-dihydropBridine group which influences the cerebral blood flow. The active substance labelled with carbon-14 was administered orally or intravenously to rats at doses ranging from 1 to 10 mg/kg. The objective of the study was to determine the course of the distribution of total radioactivity among organs and tissues, to investigate the extent and kinetics of diaplacental transfer and to study the influence of continuous treatment over three weeks on concentrations and elimination kinetics in organs and tissues. The radioactivity concentration was determined qualitatively by whole-body autoradiography or quantitatively after autopsy. Following intravenous administration the radioactivity of [14C]nimodipine is distributed rapidly and uniformly. Later, and also after oral administration, the distribution pattern is strongly differentiated with high concentrations in the liver, kidneys and fat and low concentrations in the brain and testes and subsequently in the plasma. Within one day the concentration in the animal excluding the gastrointestinal tract falls by a factor of 25 and a slow elimination phase then ensues. Only a little of the radioactivity of nimodipine passes through the placental barrier. The distribution patterns and excretion routes detected in the foetus are essentially the same. The radioactivity concentration in the foetus was a factor of 8-15 lower than in the dam.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

[Enzyme determination in the urine for the evaluation of kidney tolerance of the water-soluble roentgen contrast medium iopamidol].

The renal toxicity of the ionic, very hyperosmolaric megluminamidotrizoate was compared with the toxicity of the non-ionic, slightly hypertonic iopamidol after intravenous injection of 0.7 ml/kg body weight (i.e. about 300 mg iodine/ml) in a randomized study of 20 individuals with normal kidneys. Quantitative measurements of the excretion of the enzymes, lactate dehydrogenase (LDH), alkaline phosphatase (AP), and N-acetylglucosaminidase (NAG) in 24-h urine samples, serum creatinine, and the endogeneous creatine clearance were conducted to determine the possible renal damage. All 20 subjects tolerated both contrast mediums well. Reduced renal function as measured by the creatinine blood level and the endogeneous clearance did not occur. The ionic, hyperosmolaric megluminamidotrizoate++ caused significantly elevated enzymuria of NAG, AP, and LDH (P less than 0.01) following tubular irrigation, whereas iopamidol showed no significant enzymuria. Therefore, it appears that the non-ionic contrast medium, iopamidol, is less toxic for kidneys than the ionic megluminamidotrizoate.

Acetylglucosaminidase↗
PubMed1983

[Methodological aspects of urinary enzymology].

Collection and storage of the sample exert significant influences on the results of urinary enzyme determinations. Enzymes with sufficient stability during urine collection and consecutive in vitro storage are probably best suited for diagnostic purposes. Sample preparation, e.g. by gel filtration of the urine should be performed to remove quantitatively interferences. Optimized methods for some urinary enzymes are now available offering a basis for standardization. Analytical results should be verified by the use of self-prepared or commercially available quality control materials. The modern clinical chemical technology permits the determination of enzyme activities in urine with a quality standard comparable to that in other body fluids. New approaches are the development of a dipstick test for beta-N-acetylglucosaminidase and the use of immunological techniques for the measurement of enzyme concentrations in urine.

Acetylglucosaminidase↗