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Biomedical subjects

K Baumann

Publications and source records attributed to K Baumann.

At least 55 records · Page 3Linked to original sources
PubMed1990

Cyclosporine A induced lipid peroxidation and influence on glucose-6-phosphatase in rat hepatic and renal microsomes.

The in vitro effect of cyclosporine A (CsA) on lipid peroxidation (LPO) in hepatic and renal microsomes (male Wistar rats) were investigated either with different CsA concentrations (0.3-1000 micrograms/ml), incubation time 3 h or for different periods of time (0.5-3.0 h) at a CsA concentration of 1000 micrograms/ml. LPO was monitored by measuring the formation of malondialdehyde (MDA) using the thiobarbituric acid assay. Furthermore the influence of CsA on the microsomal enzyme glucose-6-phosphatase was investigated. CsA caused a time- and concentration-dependent increase of LPO in hepatic and renal microsomes. The lowest CsA concentration which produced a significant increase in MDA production amounted to 1 microgram/ml for hepatic microsomes and 3 micrograms/ml for renal microsomes. Under identical experimental conditions, the MDA production by hepatic microsomes was 3 to 5 fold higher than by renal microsomes. Addition of the radical scavenger alpha-tocopherol (1 mM) to the incubation medium decreased the CsA-caused microsomal MDA production. Regarding the microsomal enzyme, CsA decreased the specific activity of glucose-6-phosphatase in a time- and concentration-dependent fashion. Compared to microsomal MDA production, higher CsA concentrations were necessary to effect on specific enzyme activity. The results suggest, that production of free radicals and subsequently lipid peroxidation could participate in cyclosporine A induced hepato- and nephrotoxicity.

Animals↗
PubMed1989

Sex differences in nephrotoxic and gastrointestinal effects of phenylbutazone.

Male and female Wistar rats were used to study the sex differences in nephrotoxic, ulcerogenic and lethal effects of phenylbutazone (PBZ). In one series of experiments, male and female rats were given daily oral doses of 25, 125, 250, 400 and 500 mg PBZ/kg for 7 days to assess mortality, gross and microscopic lesions of the stomach, intestine and kidneys and to determine the PBZ effects on renal protein and glucose excretion. In another series of experiments, PBZ effects on renal gluconeogenesis and p-aminohippurate (PAH) accumulation in renal cortical slices were measured 12 h after administration of the same PBZ doses to male and female rats. Reduced glutathione (GSH) depletion and malondialdehyde (MDA) content in kidney cortex and liver were determined 2 h after a single administration of 250 mg PBZ/kg to male and female rats. To measure the effects of PBZ on blood urea nitrogen (BUN), male and female rats were given a single dose of PBZ (125 mg/kg) and were sacrificed at different time intervals, from 0 to 48 h. Gross and microscopic examination of the kidneys and gastrointestinal tract showed more pronounced renal and gastrointestinal lesions in surviving female than in male rats at the same doses. In PBZ treated male rats, BUN did not differ from control rats 48 h after PBZ administration. In female rats, BUN increased from 18 to 96 mg/100 ml 48 h after PBZ administration. After 7 days of PBZ treatment there was a greater increase of protein excretion in female than in male rats, but there were almost no sex differences in glucose excretion. Twelve hours after PBZ administration, renal PAH accumulation and gluconeogenesis were not different from controls in male rats but decreased in a dose-dependent fashion in females. A significant depletion of GSH and a significant increase in MDA content in liver and renal cortex occurred in female but not in male rats. In conclusion, the PBZ treatment was associated with nephrotoxic and gastrointestinal effects which could be detected earlier and were greater in female than in male rats.

Animals↗
PubMed1989

Computer analysis reveals changes in renal Na+-glucose cotransporter in diabetic rats.

A novel, computer-assisted program was developed to analyze the time course of Na+-glucose cotransport by rat renal cortical brush-border membrane vesicles (BBMV). Transporter characteristics can be measured, which routine kinetic analyses fail to distinguish: cotransporter membrane density is derived from the picomoles of D-glucose bound per milligram of protein. Binding is stereospecific, blocked by phlorizin, and supported equally well by Na+ or K+ (but not Cs+). Quasi-first-order influx and efflux rate constants for the composite Na+-driven influx and the (presumed) Na+-independent efflux processes were highly dependent on glucose concentration. Either two Na+-glucose transporters exist in proximal tubules or a single mechanism abruptly changes rate when glucose falls to low levels. The major operation mode is slow, has a high capacity but low affinity, and may have a 2 Na+:2 glucose stoichiometry (Hill coefficient is unity). The minor system is a fast, smaller-capacity, higher-affinity operation with a 2 Na+:1 glucose stoichiometry that was not distinguishable when the same data were analyzed in conventional kinetic plots. Results with streptozocin-induced diabetic rats illustrate the method's utility. Low-glucose-affinity cotransporters were upregulated in hyperglycemic, but not in cachectic, ketoacidotic animals. Rate constants, especially for efflux, were decreased in diabetes.

Animals↗
PubMed1988

Nephrotoxic potential of first-, second-, and third-generation cephalosporins.

First-, second-, and third-generation cephalosporins were investigated for their peroidative and nephrotoxic potential. Renal cortical slices from male Wistar rats were incubated at 37 C for 1 h in a phosphate-buffered medium containing the cephalosporin (1.25, 2.5, 5 or 10 mg/ml). In another series of experiments 5 mg/ml cephalosporin was incubated under the same conditions for 30, 60, 90 and 120 min. Subsequently, slices were incubated for 60 or 90 min in a bicarbonate- or phosphate-buffered medium containing pyruvate or tetraethylammonium (TEA) to determine gluconeogenesis and TEA accumulation, respectively. The peroxidative potential was determined at the end of the first incubation by measuring the increase in the malondialdehyde (MDA) content in renal cortical slices. The nephrotoxic potential was determined at the end of the second incubation by measuring the decrease in accumulation of the organic ion (TEA) and decrease of pyruvate-stimulated gluconeogenesis in renal cortical slices. First-generation cephalosporins, cephaloridine and cephalothin showed a time- and concentration-dependent increase in MDA content and a decrease in TEA accumulation and gluconeogenesis by renal cortical slices. Cefazolin, another first generation cephalosporin, showed a weak peroxidative and practically no nephrotoxic potential. In the group of second-generation cephalosporins, cefotiam showed a weak peroxidative potential comparable to that of cefoxitin but had a much greater nephrotoxic potential which was similar to that of cephaloridine. The third-generation cephalosporins, cefotaxime and cefoperazone showed a low peroxidative and no nephrotoxic potential.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Cisplatin-induced lipid peroxidation and decrease of gluconeogenesis in rat kidney cortex: different effects of antioxidants and radical scavengers.

The present in vitro study was performed to investigate the effect of the nephrotoxic anticancer agent cisplatin (CP) on lipid peroxidation, on pyruvate-stimulated gluconeogenesis and on p-aminohippurate (PAH) accumulation in rat renal cortical slices. In addition, the inhibitory effects of the antioxidants and radical scavengers N,N'-diphenyl-p-phenylenediamine (DPPD), (+)-cyanidanol-3 or alpha-tocopherol on CP-induced lipid peroxidation and CP-induced decrease of gluconeogenesis and the inhibitory effect of DPPD on CP-induced decrease of PAH accumulation were evaluated. Slices were incubated in a CP-containing medium for different periods of time (7.5-300 min) and at different concentrations (0.025-1.5 mg/ml). Lipid peroxidation was monitored by measuring the production of malondialdehyde (MDA). Accumulation of PAH was expressed as slice to medium concentration ratio. Pyruvate-stimulated gluconeogenesis, measured as glucose production, was determined after a subsequent 60- or 15-min incubation in a pyruvate-containing, CP-free medium. CP led to a time- and concentration-dependent increase in MDA production, a time- and concentration-dependent decrease of pyruvate-stimulated gluconeogenesis and a time-dependent decrease of PAH accumulation in renal cortical slices. Decrease of gluconeogenesis preceded MDA production and decrease of PAH accumulation. Antioxidants reduced CP-induced MDA production and CP-induced decrease of accumulation of PAH, but did not reverse CP-induced decrease of gluconeogenesis. This might indicate, that the generation of free radicals and subsequent lipid peroxidation may play a role, at least in part, in inducing CP nephrotoxicity. There could be more than one mechanism of CP-induced nephrotoxicity, since decrease of gluconeogenesis preceded MDA production and decrease of PAH accumulation and could not be inhibited by antioxidants and radical scavengers.

Animals↗
PubMed1988

Inhibition of lactate-dehydrogenase by cisplatin and other platinum-compounds: enzyme leakage of LDH is not a suitable method to measure platinum-compound-induced kidney cell damage in vitro.

The effects of three platinum-compounds on the activity of hog muscle lactate-dehydrogenase (LDH), cytosolic LDH released from rat renal cortical slices and cytosolic LDH isolated from rat kidney cells were investigated. In vitro, cisplatin inhibited the activity of LDH in a concentration-dependent manner. At a concentration of 0.25 mg/ml, cisplatin, transplatin and cisplatin-hydrolysis-products inhibited the activity of LDH time-dependently. These observations make it doubtful to use LDH-enzyme leakage experiments to demonstrate damage of kidney cells by platinum-compounds. The nonnephrotoxic compound transplatin had an enhanced inhibitory effect on the activity of LDH compared to the nephrotoxic compounds cisplatin or cisplatin-hydrolysis-products (transplatin greater than cisplatin greater than cisplatin-hydrolysis-products). Thus, LDH-enzyme inhibition seems not to be related to the nephrotoxicity of cisplatin.

Animals↗
PubMed1988

Cyclosporine A induced lipid peroxidation in microsomes and effect on active and passive glucose transport by brush border membrane vesicles of rat kidney.

The in vitro effect of cyclosporine A (CsA) on lipid peroxidation (LPO) in rat renal microsomes were investigated either with different CsA concentrations (0.001 to 1.5 mg/ml) or for different periods of time (0.5 to 3 h). Furthermore the influence of this drug on glucose uptake by rat renal brush border membrane vesicles (RBBMV) prepared from renal cortical slices which were preincubated with CsA for 1 or 3 h was studied. CsA caused a time- and concentration-dependent increase of malondialdehyde production in renal microsomes. LPO was inhibited by addition of the radical scavenger alpha-tocopherol. Regarding the CsA effect on the vesicular glucose uptake, an increase in the passive influx constants of L-glucose and a decrease in the maximal transport rates of the sodium-dependent D-glucose uptake were found as compared to the corresponding control values. The apparent affinities of D-glucose to the glucose transporter were slightly lowered after incubation of slices in a CsA containing medium. The results of the present study suggest that CsA causes LPO in renal microsomes and that this LPO is due to membrane damage by CsA as shown by alternations of active and passive glucose uptake by RBBMV.

Animals↗
PubMed1985

Inhibition of cephaloridine-induced lipid peroxidation.

The present study was designed to elucidate whether cephaloridine-induced lipid peroxidation is inhibited by probenecid, cobalt chloride and antioxidants such as alpha-tocopherol and N,N'-diphenyl-p-phenylenediamine (DPPD). Kidney slices obtained from the renal cortex of male Wistar rats were incubated for 1 h in a cephaloridine or cefotaxime (1.25-10 mg/ml) containing medium. In another series of experiments, kidney slices were incubated with cephaloridine or cefotaxime (5 mg/ml) for different periods of time (30-120 min). Lipid peroxidation was monitored by measuring the production of malondialdehyde (MDA). Subsequently, kidney slices were incubated in both series of experiments, in a cephalosporin free medium containing tetraethylammonium (TEA). Accumulation of TEA in renal cortical slices, expressed as slice to medium ratio (S/M), was used to measure changes in the transport capacity of the kidney cells. While cefotaxime had only a slight effect, cephaloridine induced a significant time- and concentration-dependent increase of MDA production and a significant time- and concentration-dependent decrease of TEA accumulation. Inhibition of the renal uptake of cephaloridine by probenecid induced a decrease in MDA production and complete recovery of TEA accumulation. The antioxidants DPPD and alpha-tocopherol inhibited cephaloridine-induced lipid peroxidation in a concentration-dependent manner. Recovery of TEA accumulation accompanied the decrease in lipid peroxidation. DPPD was a more potent inhibitor of lipid peroxidation than alpha-tocopherol. Cobalt chloride, known for its ability to decrease cellular concentration of cytochrome P-450, effectively decreased cephaloridine-induced lipid peroxidation. Thus, these findings support the concept that lipid peroxidation has an important role in the development of cephaloridine-induced nephrotoxicity.

Animals↗
PubMed1985

Cephaloridine-induced lipid peroxidation initiated by reactive oxygen species as a possible mechanism of cephaloridine nephrotoxicity.

Rat kidney microsomes reduced cephaloridine when incubated anaerobically with NADPH. Superoxide anion was generated in a concentration- and time-dependent manner when cephaloridine was incubated with rat kidney microsomes. Cephaloridine increased the in vitro peroxidation of rat kidney microsomal lipids in a concentration- and time-dependent manner. Cephaloridine-induced lipid peroxidation was inhibited by a combination of superoxide dismutase and catalase, by the hydroxyl radical scavengers, mannitol, (+)-cyanidanol-3 and by the singlet oxygen scavenger histidine in a concentration-dependent manner. It is proposed that cephaloridine nephrotoxicity may occur through the transfer of an electron from reduced cephaloridine to oxygen and subsequent formation of the superoxide anion, hydrogen peroxide, the hydroxyl radical and singlet oxygen. These activated oxygen species then are very likely to react with membrane lipids to induce lipid peroxidation and nephrotoxicity.

Anaerobiosis↗
PubMed1985

Kinetic studies of D-glucose transport in renal brush-border membrane vesicles of streptozotocin-induced diabetic rats.

Renal brush-border membrane vesicles prepared from streptozotocin-induced 4-day-diabetic rats possessed a Na+-dependent D-glucose transport system that exhibited apparent Kt and Vmax values about 2-fold greater than normal. Apparently, hyperglycemia and probably other stimuli cause the induction and membrane incorporation of a low-affinity transporter in these membranes; this increased sugar-transport capacity is retained for at least 4 weeks so long as the animals maintained or increased their body weight. Membranes prepared from 28-day-diabetic, severely ill ketoacidotic animals lose this enhanced transport ability and the decrease in Vmax was found to correlate directly with the weight loss. Furthermore, the transporter in brush-border membranes prepared from these cachectic animals had an even lower affinity for glucose than those from the acute hyperglycemic animals. That these changes in the diabetic animals represent major alterations in renal brush-border membrane construction is further supported by our observation that the specific activity of the marker enzymes, alkaline phosphatase and neutral alpha-glucosidase, are profoundly increased and decreased, respectively, in this condition.

Alkaline Phosphatase↗
PubMed1985

Inhibition of protein reabsorption in the renal proximal tubule by basic amino acids.

The effects of basic and neutral amino acids on the reabsorption of 125I-lysozyme by the renal proximal tubule were examined in rats. In whole animal experiments control animals were given an intravenous (i.v.) injection of 125I-lysozyme alone while experimental animals received an i.v. injection of either a basic or a neutral amino acid prior to the injection of 125I-lysozyme. In control animals the renal content of 125I-lysozyme 30 min after injection was 35% of the injected dose. After injection of basic amino acids there was a significant decrease in the renal uptake of lysozyme. There was no effect of neutral amino acids on the reabsorption of lysozyme. In microperfusion experiments proximal convoluted tubules were perfused in vivo for 3 min with a solution containing 125I-lysozyme and either lysine or alanine. In tubules perfused with lysine there was a significant decrease in the reabsorption of lysozyme, whereas alanine had no effect on lysozyme uptake. Electron microscope autoradiography revealed that lysozyme was located in endocytic vesicles and lysosomes in both experimental groups. However, the autoradiographic grain density was significantly decreased in tubules perfused with lysine as compared with those perfused with alanine. These findings demonstrate that basic amino acids inhibit the reabsorption of the cationic protein lysozyme by the proximal tubule cells.

Absorption↗
PubMed1984

Effect of low-molecular-weight proteins on protein (lysozyme) binding to isolated brush-border membranes of rat kidney.

Filtered proteins including the low-molecular-weight protein lysozyme are reabsorbed by the proximal tubule via adsorptive endocytosis. This process starts with binding of the protein to the brush-border membrane. The binding of 125I-labelled egg-white lysozyme (EC 3.2.1.17) to isolated brush-border membranes of rat kidney and the effect of several low-molecular weight proteins on that binding was determined. The Scatchard plot revealed a one-component binding type with a dissociation constant of 5.3 microM and 53.0 nmol/mg membrane protein for the number of binding sites. The binding of the cationic lysozyme was inhibited competitively by the addition of cationic cytochrome c to the incubation medium, while the neutral myoglobin had no effect. The anionic beta-lactoglobulin A inhibited the lysozyme binding in a noncompetitive manner. These data suggest that the binding takes place between positively charged groups of the protein molecule and negative sites on the brush-border membrane, and, the competition between the cationic cytochrome c and the cationic lysozyme for the binding sites may be responsible for the inhibitory effect of cytochrome c on renal lysozyme reabsorption. The binding step at the brush-border membrane appears to be cation-selective.

Animals↗
PubMed1984

Renal processing of low molecular weight proteins.

Previous renal clearance studies provided quantitative data concerning renal reabsorption of proteins while the simultaneous processes of renal accumulation and degradation remain, to a great extent, insufficiently investigated. Thus, it was the aim of this study to measure renal reabsorption of egg-white lysozyme at various lysozyme concentrations and to relate the corresponding accumulation and degradation of lysozyme to the lysozyme transport rates in intact rats and isolated perfused rat kidneys. Lysozyme (with 125I-lysozyme in certain experiments), was continuously infused i.v. or added to the perfusate to achieve plasma (or perfusate) concentrations of lysozyme (PLY) of approximately 50, 500 or 1000 mg X 1(-1) for periods of time varying between 3 and 120 or 150 min. Clearances of inulin and lysozyme or the total content of radioactivity and the trichloroacetic acid (TCA)-soluble radioactivity in the kidney tissue were determined at the end of clearance or accumulation periods. Additionally the perfusate concentration of the metabolite tyrosine was measured by high performance liquid chromatography (HPLC). The reabsorption rates of lysozyme (TLY) were concentration-dependent in both intact rats and isolated perfused rat kidney. After 25 min of lysozyme infusion, the lysozyme reabsorption rates amounted to 37, 245 and 331 micrograms X min-1 X g-1 kidney at the above lysozyme concentrations. After the same infusion time, the accumulation rates of lysozyme were 8, 59 and 118 micrograms X min-1 X g-1 kidney. The difference between the transport rate and accumulation rate should represent the renal degradation rate of lysozyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Dependence of renal protein reabsorption on glomerular filtration rate and infusion time.

Egg-white-lysozyme was infused into rats intravenously to achieve plasma concentrations of lysozyme (PLy) in the range of 10-3,500 mg X l-1. Concentrations of inulin and lysozyme in plasma and urine samples were determined spectrophotometrically. The glomerular filtration rate (GFR) was measured as clearance of inulin. The lysozyme reabsorption rate (TLy) was calculated as the difference between the filtered load and excreted amount of lysozyme. TLy increased with increasing filtered loads of lysozyme up to 1,000 micrograms X min-1 whether the increase in load was caused by an increase in PLy or GFR. These TLy were not dependent upon lysozyme infusion time. At lysozyme loads above saturation of reabsorption (1,000 micrograms X min-1) TLy was dependent on GFR and on the passed time after onset of lysozyme infusion. The results of this study indicated that the transport rate of lysozyme is a function of PLy, GFR and duration of lysozyme delivery to tubular cells.

Absorption↗
PubMed1984

Nephrotoxic effects of aminoglycoside treatment on renal protein reabsorption and accumulation.

To quantify the effects of gentamicin, kanamycin and netilmicin on renal protein reabsorption and accumulation, these drugs were administered to rats intraperitoneally (30 mg/kg/day) for 7, 14 or 21 days. Scanning electron microscopy of the glomerular endothelia, urinary measurements of sodium, potassium, endogenous lysozyme, N-acetyl-beta-D-glucosaminidase (NAG) as well as clearance and accumulation experiments after i.v. administration of egg-white lysozyme and measurements of inulin clearance (GFR) were done in each treatment group. Gentamicin administration decreased diameter, density and shape of endothelial fenestrae. Kanamycin and netilmicin appeared to have no effect at the dose used. All three aminoglycosides decreased GFR and increased urinary excretion of sodium and potassium. While gentamicin and kanamycin decreased the percentage reabsorption and accumulation of lysozyme after i.v. administration of egg-white lysozyme netilmicin had no effect. Daily excretion of total protein, endogenous lysozyme and NAG increased only after treatment with kanamycin and gentamicin. Thus, aminoglycosides may act as nephrotoxicants at glomerular and/or tubular level inducing impairment of renal reabsorption and accumulation of proteins.

Absorption↗