摘要:

Cell death releases products of chromatin catabolism, particularly DNA, which can be measured by a DNA assay (using the nick translation reaction) as a marker of toxicity. Conditions for blood and urine collection have been established for quanti-tation of extracellular DNA in mice. Toxic doses of lipopolysaccharide (5 mg/kg) and HgC2(3.2 mg/kg) release DNA to plasma and urine. Increase in urinary DNA is observed 24 hours after a single injection (5 mg/kg) of gentamicin. Quantitation of extracellular DNA can be used to investigate the occurrence of cell death in vivo and applied to toxicological studies, in animals and man.

ISSN:0886-022X    

DOI:10.3109/08860229009065555

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Renal function was assessed in 20 (11 female and 9 male, age 21–76 years, mean 53) renal patients with a creatinine clearance 25–145 ml/min, mean 95, to evaluate the effects of iohexol, a non-ionic low-osmolar contrast medium. Intravenous urography was performed in 16 patients and computed body tomography in 4, using a dose of iohexol ranged between 0.6–3.3 (mean 1.17) g/kg b.w. Different parameters of renal function were determined in the week preceding and 1, 3 and 5 days after the administration of iohexol. The principal renal effect of iohexol was an increase of urinary alanine aminopeptidase, gamma-glutamyltransferase, lactate dehydrogenase, alkaline phosphatase and N-acetyl-β-D-glucosaminidase. The maximun increase of enzymuria was observed on day 1 after the administration of iohexol. In most cases enzymes returned to base-line values within 3 days. No relevant variation of renal hemodynamics (glomerular filtration rate and effective renal plasma flow) was observed after iohexol. In conclusion, iohexol can increase of urinary enzymes, but the effect is rapidly reversible and is not accompanied by a clinically significant impairment of renal hemodynamics.

ISSN:0886-022X    

DOI:10.3109/08860229009065556

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The effects of oxidative damage were assessed in rat proximal tubule fragments (isolated by collagenase perfusion) by monitoring lactate dehydrogenase release (LDH-R) to measure cell viability and thiobarbituric acid (TBA) reactive material to follow oxidative damage. Increasing the oxygen content in the incubation atmosphere from 10 to 95% significantly increased LDH-R and TBA reactants. Addition of butylated hydroxytoluene or deferoxamine (DF) to the medium prevented these changes, but ascorbic acid or mannitol had no positive effect. Lima bean trypsin inhibitor also reduced LDH leakage significantly when added to the medium, but not when added to the perfusion buffers. In contrast, adding DF to the perfusate during tubule isolation produced the most pronounced benefit; net LDH-R after 4 hr was about 10% in tubules prepared this way compared to 20% when DF was omitted. Basal oxygen consumption declined to approximately the same extent as LDH-R increased. Maintenance of nystatin-stimulated respiration, ATP/ADP, GSH content and total adenine nucleotides indicated good cell function. These results suggest that oxidative damage initiated during the tubule isolation procedure limits cell survival but this effect can be counteracted substantially by the addition of DF to the perfusion buffer.

ISSN:0886-022X    

DOI:10.3109/08860229009065557

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Large White pigs were used to investigate the effects of acetaminophen (paracetamol) on normal kidneys or those with an existing renal papillary necrosis. Pairs of young female animals were treated with either a single iv dose of 50 mg/kg 2-bromoetha-namine (BEA), 100 mg/kg/day acetaminophen po for 28 days, or a combination of BEA followed by the acetaminophen treatment. Two pigs served as untreated controls. Kidney length, diameter and parenchymal thickness were measured by ultrasound scans, and glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) assessed by99mTc-DTPA and131I-hippuran renography prior to treatment and on day 26. Acetaminophen only caused no renal pathology. Despite the lack of a gross RPN, hyperplasia of the pelvic and ureteric urothelia (with extensive vacuolation) was observed following BEA, but BEA followed by acetaminophen for 28 days did not enhance the lesion. The BEA and BEA-acetaminophen groups (but not acetaminophen only) showed an increased ERPF compared with age-matched contols, but there was no significant difference in the overall GFR between the groups.

ISSN:0886-022X    

DOI:10.3109/08860229009065558

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The effect of cyclosporine A (CsA) on lipid peroxidation (LPO) was assessed in renal cortical slices and renal microsomes. Cortical slices were incubated with 1500μg/ml CsA and microsomes with 0.5–20μg/ml under identical conditions (pH 7.4,37d`C) for 3 hours, and LPO monitored by the formation of malondialdehyde (MDA). CsA at concentrations of 3μg/ml and higher caused a significant increase MDA in microsomes and renal cortical slices showed a time dependent release of MDA into the incubation medium. The influence of CsA on tetraethammonium (TEA) and p-ami-nohippurate (PAH) accumulation in renal cortical slices was investigated for up to 3 hours with concentration of CsA from 10 to 1000μg/ml. CsA caused a time-and concentration-dependent decrease of TEA accumulation and higher concentrations of CsA decreased PAH accumulation in renal cortical slices. The results add further evidence to the suggestion that lipid peroxidation participate in CsA-induced impairment of kidney function.

ISSN:0886-022X    

DOI:10.3109/08860229009065559

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The protective effect of the platelet-activating factor (PAF) antagonist, BN 52021, was assessed on cis-diammine-dichloroplatinum (CDDP)-induced nephrotoxicity. Wistar male rats were treated with either a single dose of CDDP (10 mg/kg b.w. ip) alone or in association with 7 daily doses of BN 52021 (10 mg/kg b.w. ip). At the end of the experiment, the CDDP-treated rats lost 25% of body weight and serum creatinine and urea increased from 0.041±0.006 mmol/1 and 0.165±0.007 g/1 for the control group to 0.202±0.019 mmol/1 and 1.51±0.131 g/1 versus CDDP respectively. Body weight, serum creatinine, serum urea and creatinine clearances were similar to the control group in animals treated with CDDP and BN 52021. CDDP caused proximal tubular necrosis and dilatation of cortical collecting tubes, changes that were markedly less in the BN 52021-protected animals. The concomitant administration of BN 52021 with CDDP did not modify the plasma pharmacokinetic of CDDP. In addition, BN 52021 did not interfere with the antiproliferative and antitumoral actions of CDDP in cultured human tumor cells. BN 52021 therefore could prevent the nephrotoxicity of CDDP.

ISSN:0886-022X    

DOI:10.3109/08860229009065560

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Freshly isolated rabbit proximal tubules (PT), confluent primary rabbit proximal tubule cultures (PTC) and LLC-PK1 cells were characterised. Brushborder enzyme activities were lower in PTC than in LLC-PK1: ratios were 0.026 for alkaline phosphatase (AP), 0.458 for alanine aminopeptidase (AAP) and 0.514 for gamma-glutamyl transpeptidase (GGT). PT/PTC ratios were 79.7 for AP, 7.96 for AAP and 3.45 for GGT. Specific activities of hexokinase (HK) and lactate dehydrogenase (LDH) were high in cultured cells as compared to PT: PT/PTC ratios were 0.063 and 0.033, while PTC/LLC-PK1 ratios were 0.406 and 1.19 for HK and LDH respectively. PTC/LLC-PK1 ratios were 2.21 forNa/K ATPase, 2.07 for succinate dehydrogenase, 1.12 for cathepsin B, 0.607 for N-acetyl-β-D-glucosaminidase and 8.98 for gluta-thione-S-transferase. Adenylate cyclase response to parathormone (PTH), was similar in PTC and PT, but stimulated/basal ratios were higher in PT than in PTC. LLC-PK1 cells were stimulated by thyrocalcitonin(SCT),arginin-vasopressin (AVP) and PTH; stimulated/basal ratios ranked AVP>PTH>SCT. Differences between both types of cultures affect the choice of in vitro model for nephrotoxicity studies.

ISSN:0886-022X    

DOI:10.3109/08860229009065561

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Cellular toxicity and cellular carcinogenesis are closely linked. In the kidney, this relationship has been emphasized by the recent discovery of a number ofputatively non-mutagenic chemicals that result in acute and chronic toxicity and ultimately in carcinogenesis, especially in the male rat. Many, but not all such compounds, result in renal PTE phagolysosomal overload. At the same time, known metabolites of other carcinogens, e.g., HCBD and FBPA, result in acute renal injury andlor necrosis, followed by chronic tubular disease, interstitial nephritis, and ultimately carcinogenesis. A series of cell mechanisms have been suggested that lead from acute cell injury to altered control of cell division. These mechanisms appear to involve ion deregulation, (especially [Ca2+]i) resulting from a variety of continued injuries, (e.g., oxida-tive stress from inflammatory cells) and ultimately leading to altered gene expression.

ISSN:0886-022X    

DOI:10.3109/08860229009065562

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Children with various grades of renal insufficiency (CON group) maintained uric acid excretion over a range of glomerular filtration rate (GFR) from 27 to 160 ml/min*l. 73m2despite a decreased filtered load which was paralleled by glomerular filtration of uric acid. This was achieved by a compensatory decrease of net uric acid reabsorption (Tua) and an increasing fractional excretion of uric acid (FEua) with decreasing GFR. Although there was a decreased GFR in the group of children after transplantation (NTx group) there was no difference in Tua and FEua between the NTx group and the CON group. Uric acid transport was not affected in children treated with Cyclosporine (CyA)for nephrotic syndrome (NEPH group) compared to the CON group. Decreased fractional phosphate reabsorption in the NTx group suggests proximal tubule damage associatedwith disturbed uric acid handling. Under conditions of water diuresis hyperuricemia seen in NTx may result from an indirect effect of renal ischemic damage due to the transplantation procedure causing disturbance of proximal tubular uric acid (active) secretionlreabsorption.

ISSN:0886-022X    

DOI:10.3109/08860229009065563

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The safety, pharmacokinetics and efficacy of one daily injection (qd) of amikacin (AK) and netilmicin (NT) was compared with the recommended schedules (cs), i.e. twice-daily or thrice-daily, respectively. Women (17–43 years, n = 78) suffering from pelvic inflammatory disease were randomly assigned to qd or cs of either AK (14 mg/kg per day) or NT (6.6 mg/kg per day). Biometric parameters were similar in the 4 groups and all patients recieved ampicillin (4 g/day) and tinidazole (0.8 g/day). The Repeated Measures Analysis of Variance was used to distinguish the effects of the schedules and of the drugs choice on critical parameters. Efficacy was similar in the 4 groups and not influenced by the schedule of administration. No significant differences in nephro-and oto-toxicity were observed as assessed by serum creatinine and losses of hearing at low frequencies, but early phospholipiduria and auditory losses at high frequencies were significantly reduced with the qd administration compared to cs and by AK compared to NT. These data suggest that the qd schedule of AK and of NT is as efficacious as their cs schedules, and causes less renal and auditory alterations.

ISSN:0886-022X    

DOI:10.3109/08860229009065564

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor