Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pattern of proteinuria found in patients during the administration of methotrexate (MTX) or aminoglycosides (AG) and in cadmium or Balkan nephropathy was investigated using the technique of sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). As renal tubular dysfunction increased, measured by the urinary concentration of 4 low molecular mass (LMr) proteins, SDS-PAGE bands appeared in the following order of molecular mass (Mr): 59, 44, 31, then below 31 000. The presence of bands less than 31 000 was not an early indicator of drug-induced renal damage. Tubular proteinuria could be monitored more easily by the serum and urinary measurement of any one of the LMr proteins: alpha-1-microglobulin (alpha 1m), retinol-binding protein (RBP), beta-2-microglobulin (beta 2m), except alpha-1-acid glycoprotein (AGP), than by SDS-PAGE.
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PMID:Comparison of tubular proteinuria, using sodium dodecyl sulphate polyacrylamide gel electrophoresis, in patients during methotrexate or aminoglycoside treatment or with cadmium or Balkan nephropathy. 646 14

The effect of nickel on cadmium nephro-toxicity and hepato-toxicity in rats was investigated. The administration of nickel (6 mg per kg, i.p., three days) or cadmium (6 mg per kg, i.m., once) significantly enhanced the urinary excretion of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glutamate oxaloacetate transaminase (GOT), amino acids, and proteins. In addition, it increased the activity of serum ALP, GOT, and glutamate pyruvate transaminase (GPT). These biochemical alterations in urine and serum were used as a measure of kidney and liver damage. Cadmium-induced enzymuria, proteinuria, amino aciduria and increase in the activity of serum enzymes were significantly less marked in animals pretreated with nickel than in controls. However, the accumulation of cadmium in kidneys and liver and its urinary excretion were unaffected by nickel pretreatment. The results suggest protection by nickel against cadmium nephro- and hepato-toxicity.
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PMID:Preventive effects of nickel on cadmium hepatotoxicity and nephrotoxicity. 647 83

Rats were injected daily, five days/week, with 0.6 mg Cd/kg as CdCl2 for eight weeks. Groups of rats were sacrificed weekly. Urine, plasma and tissue cadmium levels, and morphology of renal cortex were studied. No abnormal effects were found until the fifth or sixth week when cadmium in kidney reached about 100 micrograms/g tissue. At this time, renal tubular lining cells showed an increase in lysosomes, microbodies and smooth endoplasmic reticulum and a low molecular weight cadmium-binding species was detectable in plasma. These changes were followed by the onset of glycosuria and proteinuria, accompanied by abnormal mitochondrial morphology. This progressed to cellular swelling and finally necrosis at the seventh and eighth weeks when cadmium concentration of the kidney reached about 200 micrograms/g of tissue. It is concluded that there are two phases in the development of cadmium induced nephropathy. Phase I is an adaptive phase characterized by some increase in smooth endoplasmic reticulum, microbodies and secondary lysosomes and the presence of metallothionein intracellularly in liver and kidney, but no detectable metallothionein in plasma and no increase in urinary cadmium. Phase II is a toxic phase characterized by detectable low molecular weight cadmium-binding species in plasma and evidence of renal tubular dysfunction followed by lethal injury to renal tubular lining cells.
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PMID:Correlation of parameters of cadmium exposure with onset of cadmium-induced nephropathy in rats. 652 Jul 42

Pretreatment with nickel has earlier been shown to protect against cadmium intoxication. The effect of cadmium pretreatment on the nephro- and hepatotoxicity of nickel has been investigated. The administration of cadmium (6 mg/kg, i.m., once) to rats significantly enhanced urinary excretion of ALP, LDH, GOT, amino acids and proteins and increased the activity of serum ALP, GOT, and GPT, while the administration of nickel (6 mg/kg, i.p., 3 days) altered these parameters less significantly. These changes in urine and serum were used as a measure of renal and hepatic damage. The administration of nickel for three days, one week after cadmium treatment, caused significantly more marked enzymuria, aminoaciduria, proteinuria and an increase in the activity of serum enzymes than induced by either of them individually. However, cadmium pretreatment had no influence on urinary excretion or hepatic uptake of nickel, but increased renal uptake of nickel on the fourth day. The results suggest that cadmium enhances the nephro- and hepatotoxicity of nickel.
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PMID:Effect of cadmium pretreatment on nickel toxicity. 653 85

Nephrotoxicity of cadmium (Cd) was investigated using puromycin aminonucleoside (AN)-pretreated rats. AN pretreatment was performed by iv injection of 100 mg AN/kg body wt 11 days before the initial Cd injection. Since massive proteinuria and focal glomerular deposits were recognized, glomerular permeability is considered to be increased in AN-pretreated rats. AN-pretreated and intact rats were injected sc with 3 mg Cd/kg body wt, 4 times a week. In non-pretreated rats, slight tubular vacuolation was seen after 1-week Cd exposure and severe vacuolation and coagulative necrosis of the tubules was observed after 2-week Cd exposure. On the other hand, AN pretreatment delayed the onset of vacuolation and necrosis for 1 week and made the lesion milder. After 1-week Cd exposure, a larger amount of Cd was excreted into the urine of AN-pretreated rats than of non-pretreated ones, whereas Cd accumulation in the kidney and liver was lower in AN-pretreated rats than in non-pretreated ones. Thereafter, no difference in Cd concentration was recognized between two groups. From these findings, it is suggested that in early stage of Cd administration, Cd was filtered through the glomerular basement membrane modified by AN pretreatment and that this filterable Cd did not have nephrotoxic effects in AN-pretreated rats.
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PMID:A study on cadmium-induced nephropathy in rats pretreated with puromycin aminonucleoside. 661 10

The combined use of ultrastructural morphometry and X-ray microanalysis in conjunction with biochemical analysis is one approach to elucidating mechanisms of metal nephrotoxicity at the cellular level. Ultrastructural morphometry conducted on proximal tubule cells of rats exposed to low levels of methyl mercury for prolonged periods of time showed statistically significant increases in the volume densities of the lysosomal and mitochondrial compartments. These findings were associated with marked changes in lysosomal marker enzymes and mitochondrial heme biosynthesis enzymes leading to the detection of a renal porphyrinuria that occurred before changes in standard tests of renal function. Ultrastructural morphometry, X-ray microanalysis, and biochemical studies of the low-molecular-weight tubular proteinuria produced by injection of cadmium metallothionein (CdMT) showed a rapid proximal tubule cell lysosome uptake and degradation of the CdMT complex, which led to a subsequent decrease in the numerical density (Nv) and average diameter of lysosomes and to an increase in the Nv of apical pinocytolic vesicles with time. The data indicate disruption of the normal primary lysosome-pinocytolic vesicle fusion process and related development of tubular proteinuria. Ultrastructural techniques may provide information useful in elucidating mechanisms of ongoing metal-induced nephrotoxic processes when consideration is given to sampling strategies for morphometric analysis and the inherent detection limits, elemental volatility, translocation effects, and limitations of quantification for X-ray microanalysis in soft biological tissues.
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PMID:Role of ultrastructural techniques in understanding mechanisms of metal-induced nephrotoxicity. 661 93

Women over 50 years of age in 32 cadmium(Cd)-polluted and 16 nonpolluted hamlets were studied. Itai-itai disease patients and proteinuria with glucosuria were used as indices of the effect of Cd on health. Unpolished rice samples were collected from 568 households in the same area and analyzed for Cd. The hamlet's average Cd concentration in rice was used as an index of Cd exposure. A close relationship between Cd exposure and health effects was found to exist when the women were classified according to their hamlet average rice-Cd concentrations. It is demonstrated that a dose-response relationship between Cd exposure and itai-itai disease exists.
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PMID:The relationship between itai-itai disease among inhabitants of the Jinzu River basin and cadmium in rice. 662 20

Cadmium metallothionein (CdMT) nephrotoxicity was studied in rats injected i.p. with a single nonlethal dose of CdMT (0.6 mg of Cd per kg). Within 8 hr of CdMT injection, urine volume and urine sodium excretion were increased and sodium dodecyl sulfate gel electrophoresis of urine proteins showed that elevated levels of low molecular weight proteins were present in the urines of CdMT-treated rats. Urine RNAase activity was also elevated, approximately 7-fold, by CdMT but not by zinc metallothionein (ZnMT) or lysozyme at equivalent protein doses, demonstrating that a proteinuria indicative of proximal tubule cell dysfunction develops as an early response to CdMT exposure. Ultrastructural alterations were also present in animals injected with CdMT but not ZnMT or lysozyme. The earliest alterations occurred in the lysosome compartment of the cell. By 1 hr, the number of small lysosomes in renal proximal convoluted tubule cells increased significantly with no changes in other organelle compartments. By 4 and 8 hr, there was a further increase in lysosome number with a concomitant decrease in size and a marked increase in the number of small clear apical vacuoles. Lysosomal cathepsin D activity was decreased at 4 and 8 hr after CdMT injection, and in vitro studies indicated that this effect was not due to a direct inhibition of the enzyme by Cd++ or CdMT. Thus, both lysosome size and protease activity were rapidly altered by CdMT exposure. Studies of Cd binding in the kidney suggest that non-MT-bound Cd is an important factor in CdMT-associated toxicity. Approximately 97% of the Cd present in the cytoplasm at 1 hr was non-MT-bound. Prior induction of renal MT by treatment with zinc (20 mg of Zn per kg as ZnSO4, i.p. 16 hr before CdMT injection) markedly reduced non-MT binding of Cd++ in kidneys of treated animals and inhibited the alterations in urine volume and low molecular weight protein reabsorption induced by CdMT. These data suggest that acute CdMT exposure provides an excellent system for studying the mechanism of cadmium tubular proteinuria and that the intracellular renal MT pool plays a key role in regulating this process.
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PMID:Cadmium-Metallothionein nephropathy: relationships between ultrastructural/biochemical alterations and intracellular cadmium binding. 670 45

High resolution electrophoresis was used to evaluate protein excretion patterns in six cadmium-exposed individuals with proteinuria, seven subjects with nonspecific nephropathies, and four normal unexposed subjects. The aim of the investigation was to determine (a) the type of excretion pattern (i.e., glomerular, tubular, or mixed) associated with cadmium exposure and (b) if the pattern in the cadmium-exposed individuals was distinctly different from subjects with nonspecific nephropathies. The electrophoretic results were consistent with the quantitative results for the cadmium-exposed workers. The results suggest that the pattern associated with cadmium exposure can be glomerular or mixed and that it is different (i.e., no gamma band) from nonspecific nephropathies.
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PMID:Protein excretion patterns in cadmium-exposed individuals: high resolution electrophoresis. 672 87

Twenty-one male rabbits were divided into three groups: rabbits of two groups were given pelleted food containing cadmium chloride at a dose level of 300 micrograms Cd/g over periods of 44 or 19 weeks. Rabbits of the last group were given ordinary commercial pelleted food and served as controls. Cadmium increased urinary protein and amino acid by week 19 and increased it to a remarkably high level by week 44. After cessation of cadmium exposure, rabbits of the first group (44 weeks exposure group) showed only little recovery from cadmium health effects: proteinuria and aminoaciduria were slightly improved. Depressed hepatic functions were also slightly improved, but did not return to the control level in 24 weeks. Fat and bone metabolism also remained depressed below the control level. Anemia did not also readily recover. On the other hand, rabbits of the second group (19 weeks exposure) recovered from the effects of cadmium: proteinuria and aminoaciduria in most animals disappeared soon after the end of cadmium exposure, plasma GPT fell after 1 week, and hemoglobin and hematocrit returned to normal in 6-11 weeks. The above results show that after cessation of cadmium exposure, mild cadmium-induced health effects were reversible in a short period, while more severe effects were not readily reversible. High performance liquid chromatographic (HPLC) profiles of renal and hepatic cadmium-thionein (Cd-MT) during and after exposure to cadmium showed no correlation to the degree of cadmium health effects, and therefore, did not help to elucidate mechanisms of the recovery from cadmium-induced health effects, probably because cadmium not bound with metallothionein (non-MT-Cd) is responsible for inducing renal effects.
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PMID:Reversibility of cadmium-induced health effects in rabbits. 673 56


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