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)

Recently we have reported that the proteinuria developed by workers exposed to cadmium was characterized by an increased excretion of high and low molecular weight proteins. These observations were confirmed experimentally. Female rats which were injected intraperitoneally with CdCl2 (1 mg Cd2+/kg) 5 times a week developed after 2 months of treatment a proteinuria qualitatively similar to that observed in workers exposed to cadmium. The analysis of this proteinuria by electrophoresis and gel filtration revealed an increased excretion of low and high molecular weight proteins. This animal study, which confirms previous observations on man, strengthens our hypothesis that the cadmium-induced proteinuria, classically considered as a tubular type proteinuria, is in fact a mixed type proteinuria, involving not only the tubule but also the glomerulus.
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PMID:Experimental confirmation in rats of the mixed type proteinuria observed in workers exposed to cadmium. 21 79

In rats injected with 5 micron mole CdCl2/kg, 5 days/week, metallothionein was detected in plasma by gel filtration chromatography as early as four weeks. The mean renal concentration of cadmium was 80 microgram/g. The excretion of cadmium in urine at this time was rather low and amounted to 0.01% of the total dose. The amount of metallothionein in plasma, as determined by 109Cd-binding to the 10,000 molecular weight fraction, increased markedly during week 14. Its excretion in urine, however, did not start until about 10 weeks, when the cadmium concentration in kidney approached a mean value of 212 microgram/g. Signs of renal toxicity were evident from glucosuria and proteinuria which became severe during the next four weeks. The excretion of cadmium in urine increased markedly and the majority of it was in the form of metallothionein. It is suggested that the appearance of metallothionein in plasma and urine can be used as specific indices of cadmium poisoning and that the assay of the protein in these fluids may be useful in screening for excessive cadmium exposure.
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PMID:Metallothionein in the extracellular fluids as an index of cadmium toxicity. 48 41

Male CBA-mice were exposed to cadmium by subcutaneous injection of 2-2 mumol CdCl2/kg body weight for 5 days/week for 6 months. A decrease in normal (testosterone-dependent) proteinuria was shown, and morphological examination of the seminal vesicles revealed a smaller weight and size as well as histological indication of lower secretory activity of the epithelium compared to controls. The findings are consistent with a theory implying a decreased testosterone activity in cadmium-treated animals.
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PMID:Effects on long-term cadmium exposure on the seminal vesicles of mice. 119 49

One group of male Wistar rats (Group B) was pretreated by a daily subcutaneous injection with CdCl2 during 5 days with increasing doses (0.5, 1, 1, 2 and 2 mg Cd/kg). Another group of rats (Group A) was daily given normal saline subcutaneously for 5 days. On the second day after the last injection, a single s.c. injection of 109Cd-metallothionein (CdMT, 0.4 mg Cd/kg) was given to each animal in both groups. Urinary calcium, protein, metallothionein (MT), N-acetyl-beta-D-glucosaminidase (NAG) and gamma glutamyltransferase (gamma-GT) were measured. In Group A, calciuria, proteinuria, metallothioneinuria and enzymuria was induced by CdMT. Calciuria reached a peak during 0-6 h after the administration of CdMT, thus appearing earlier than other effects. Enzymuria was displayed at 6-12 h for gamma-GT and 12-24 h for NAG. A prominent increase of proteinuria appeared at 24-48 h after the challenge of CdMT. In Group B, no significant increase of urinary calcium, protein, or NAG was observed after the CdMT injection and urinary gamma-GT was only slightly elevated, thus demonstrating the protective action of pretreatment. This study demonstrates for the first time that calciuria, one of the signs of cadmium nephrotoxicity, can be prevented by cadmium pretreatment. Urinary MT increased slightly during the 4-5 days of CdCl2 pretreatment. This is in accordance with previous observations that cadmium pretreatment induces new synthesis of MT which is likely to constitute the background for the resistance to the CdMT challenge to the kidney.
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PMID:Modulation of calciuria by cadmium pretreatment in rats with cadmium-metallothionein-induced nephrotoxicity. 136 Jul 15

The relative tissue distribution and toxicity of cadmium (Cd) and mercury (Hg) in the liver and kidneys of rats when the metals are administered as either inorganic salts or complexed with MT were studied. Male Sprague-Dawley rats were injected (i.v.) with Cd or Hg inorganic salt of chloride or in a complex of MT at a dose of 0.3 mg/kg body weight. The concentration of MT and metals in plasma and urine was monitored for 7 days, at the end of which the rats were killed. Injection of both HgCl2 and Hg-MT induced the synthesis of MT only in the kidney but not in the liver, whereas CdCl2 and Cd-MT injections induced MT synthesis in both liver and kidney, respectively. Plasma MT levels increased 3 days after CdCl2 but not after HgCl2 injection, suggesting that hepatic MT may be an important source of plasma MT under our experimental conditions. Renal toxicity was observed morphologically and by an increase in blood urea nitrogen, plasma creatinine, proteinuria in rats injected with Cd-MT and both forms of Hg. Urinary MT excretion was significantly elevated in Cd-MT injected rats compared with those injected with CdCl2. However, HgCl2 and Hg-MT injected rats showed no significant difference in urinary MT excretion. The magnitude in the renal accumulation of Hg is similar after the administration of Hg-MT or HgCl2, but our findings suggest that the site of epithelial injury may be different. Injury effects of Hg-MT localized mainly in the terminal portions of the proximal convoluted tubule and the initial portions of the proximal straight tubule whereas inorganic Hg caused necrosis in pars recta segments of the proximal tubule.
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PMID:Exogenous metallothionein and renal toxicity of cadmium and mercury in rats. 147 92

Dose- and time-related effects of Cd (II) (0.5 or 1.0 mg/kg, Cd as CdCl2.H2O, subcutaneously, daily for 48 h, 1, 3, or 6 wk) were investigated in rats. A dose-related increase in the activity of plasma alkaline phosphatase (ALP), lactate dehydrogenase (LDH), aspartate aminotransferase (GOT), and alanine aminotransferase (GPT) was evident only at 6 wk, whereas an early rise in ALP and LDH was seen at 3 wk in 1.0 mg Cd group only. The hepatic and renal metallothionein (MT) induction displayed a dose- as well as time-related increase with Cd accumulation. A significant increase in hepatic Zn and renal Cu, no change in hepatic Cu, and a slight increase in renal Zn was observed. Urinary ALP and leucine aminopeptidase (LAP) showed an initial increase at 48 h, thereafter returned to near normal. A second phase of enzymuria (ALP, LAP, GOT, GPT, gamma-glutamyl transpeptidase), proteinuria, and aminoaciduria occurred at 6 wk in a dose-related manner. The urinary excretion of specific renal enzymes appeared closely related to the MT induction and organ Cd levels.
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PMID:Biochemical response to cadmium. Dose-time effect. 171 72

Effects of cadmium intoxication on renal transport systems for various amino acids were studied. Subcutaneous injections of CdCl2, at a dose of 2 mg Cd/kg.day for 2 weeks, resulted in polyuria, proteinuria, glycosuria, phosphaturia, and aminoaciduria, as observed in chronic cadmium-intoxicated humans and experimental animals. The nature of aminoaciduria was nonspecific, including iminoacid as well as almost all species of neutral, acidic, and basic amino acids. In renal cortical brush border membrane vesicles isolated from cadmium-intoxicated rats, Na(+)-dependent transport of L-proline, L-alanine, and L-lysine was markedly attenuated, whereas the amino acid transport in the basolateral membrane vesicle was not significantly affected. Similar results were obtained in the normal membrane vesicles directly exposed to inorganic cadmium. These results indicate that cadmium intoxication impairs various Na(+)-amino acid cotransport systems in the renal brush border membrane, which leads to panaminoaciduria.
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PMID:Alteration of renal amino acid transport system in cadmium-intoxicated rats. 225 75

Effects of cadmium intoxication on renal transport systems for various organic compounds were studied. Subcutaneous injections of CdCl2 (2 mg Cd/kg.day) for two to three weeks induced marked polyuria, glycosuria, and proteinuria without altering glomerular filtration rate. In renal cortical brush border membrane vesicles (BBMV) isolated from cadmium treated rats, Na(+)-dependent D-glucose uptake was markedly attenuated, and this was due to reduction in Vmax and not Km. Likewise, Na(+)-driven L-glutamate transport and H(+)-driven tetraethylammonium transport were significantly reduced. In renal cortical basolateral membrane vesicles (BLMV) of cadmium intoxicated rats, Na(+)-dependent succinate transport was drastically reduced. These results indicate that cadmium intoxication impairs various transport systems for organic compounds in the brush border and basolateral membranes of proximal renal tubules.
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PMID:Transport of organic compounds in renal plasma membrane vesicles of cadmium intoxicated rats. 240 86

Kidney cells were isolated from rats pretreated by daily subcutaneous doses of cadmium metallothionein (CdMT: 0.05-0.2 mg Cd/kg X 5) and from non-pretreated rats. Upon exposure to CdCl2 in vitro (0-200 micrograms Cd/ml), a concentration dependent decrease in viability was observed in the non-pretreated cells, while no such decrease occurred in the pretreated cells indicating that these cells were more resistant to the toxic action of cadmium. There was a higher in vitro uptake of Cd+2 and an increased metallothionein (MT) concentration in the pretreated cells (compared to non-pretreated cells). Subcellular distribution studies revealed that Cd was mainly recovered in the "cytosol" fraction. The higher total cadmium uptake in pretreated cells corresponded to an increase of Cd in "cytosol" and "nuclear" fractions. This observation may be explained by MT-binding of Cd in the cells and is in accordance with a possible protective effect of induced MT in the pretreated cells. In order to assess whether pretreatment-induced tolerance to cadmium toxicity--indicated by the cellular studies--could also be observed in vivo, some whole animal experiments were also performed. A dose-related proteinuria was observed in non-pretreated rats after a single subcutaneous administration of 109Cd-MT at doses of 0.05 and 0.4 mg Cd/kg. Urinary total Cd, 109Cd and MT was also increased in a dose-related fashion. Cadmium concentrations in kidney were dose related and reached 19 micrograms/g wet weight. In contrast, in animals repeatedly pretreated with CdMT according to 1), no proteinuria was observed after administration of the same single doses of 109CdMT. Total Cd. 109Cd and particularly MT-concentrations in urine were lower in such pretreated animals than in in non-pretreated ones in spite of the accumulation of higher tissue concentrations of total Cd (up to 80 micrograms/g). The pretreatment was thus shown to prevent some of the acute nephrotoxicity of CdMT, possibly by means of induction of MT synthesis.
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PMID:Influence of cadmium-metallothionein pretreatment on tolerance of rat kidney cortical cells to cadmium toxicity in vitro and in vivo. 361 44

Three groups of rats (B-D) were given various daily doses of CdCl2 (0.5-2 mg Cd/kg) continuously or in intervals during time periods of 1-8 weeks. Another group of animals (A) were kept untreated. At the end of the period, selected subgroups of groups A-D were given a single subcutaneous injection of 109Cd-metallothionein (109CdMT) 0.05 or 0.4 mg Cd/kg ("challenge dose"). Subsequently, urinary creatinine, protein, Cd, 109Cd and MT and kidney cortex Cd, 109Cd and MT were determined. In group A (no long term pretreatment), an increased proteinuria was observed after the rats had received the lower of the challenge doses of 109CdMT, and an even greater increase after the higher challenge dose of 109CdMT. No such increase appeared in group B, C and D (repeatedly pretreated with CdCl2) at either of the challenge doses. Higher metallothionein concentrations in kidney cortex observed in the pretreated groups constitute a plausible explanation of the protective effects of pretreatment against the development of increased proteinuria after challenge dosing. It is likely that increasing Cd concentrations, gradually accumulating in the renal cortex (22-226 micrograms/g wet wt.) as a result of the pretreatment, served to induce the synthesis of metallothionein in the renal cortical cells, thus making them resistant to the challenge from 109CdMT.
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PMID:Resistance to acute nephrotoxicity induced by cadmium-metallothionein dependence on pretreatment with cadmium chloride. 367 31


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