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)

Four groups of cadmium-exposed persons, from different workplaces and with different types of exposure, have been followed for periods of 9-20 years. In one group the total observation time is over 30 years, since they were included in Friberg's original study. The studies include determination of inulin or creatinine clearance, protein excretion and specific indicators of renal tubular dysfunction. The results indicate that once tubular dysfunction is established, it is irreversible, even when it is minor. In some persons it was noted that the development of renal dysfunction seemed to be a multistage process. The initial stage is characterized by an increased excretion of low molecular weight proteins like beta 2-microglobulin and ribonuclease. After a period of several years with no or low exposure, there was a relatively sharp increase in excretion of total proteins and albumin and a decrease in glomerular filtration rate. This is interpreted as being the result of further increases in renal concentration of cadmium and in spread of cadmium along the tubules. Metallothionein absorption in the tubules, its catabolism and synthesis must play an important role for the development and progress of the tubular dysfunction. It was not possible to show that a decrease in glomerular filtration rate occurs before low molecular weight proteinuria.
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PMID:Long-term observations on tubular and glomerular function in cadmium-exposed persons. 637 91

The urinary excretion of Cd, Cu, and Zn was measured in rats injected with 0.5 mg/kg Cd, sc, 6 d/wk for u to 25 wk. Gel chromatographic analysis for these urinary metals were also carried out. The Cd excretion slightly increased at first, followed by a rapid increase with concurrent appearance of proteinuria around 6 wk. During these early weeks, excretion of Cu in the urine showed a more pronounced increase and reached a plateau level (three to four times the control value). Zn excretion showed a sharp increase accompanied by proteinuria, following a slight increase, and reached about 10 times the control value. A linear relation was obtained between Cd and both Cu and Zn in the urine before proteinuria appeared. Metallothionein (MT) in the urine was associated only with Cu before the appearance of proteinuria. Cu-MT increased with increasing excretion of urinary Cu. Cd-containing MT first appeared in the urine after on onset of proteinuria, but it was still rich in Cu at first. Fron 10 wk, urinary MT showed an excess increase and contained much Cd than Cu. Zn-MT was not observed in the urine. Most of the urinary Zn was recovered from the lower-molecular-weight fractions. The results suggest that MT is directly involved in urinary excretion of Cu in the absence of renal damage and in the excretion of Cd as well as Cu after the appearance of toxicity in Cd-exposed rats.
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PMID:Cadmium, copper, and zinc excretion and their binding to metallothionein in urine of cadmium exposed rats. 734 69

Streptozotocin-induced diabetic rats and normal non-diabetic (ND) rats were exposed to cadmium chloride in drinking water in doses of 0, 50 and 100 ppm for 90 days. There was a dose-related increase in urinary protein and enzymes in the diabetic group, but an increase in proteinuria only in the high exposure subgroup of the ND group. It is suggested that diabetic rats induced by streptozotocin are more susceptible to cadmium nephrotoxicity than normal (ND) rats. Metallothionein synthesis in liver was estimated to be similar in both the diabetic and non-diabetic groups after exposure to cadmium. Less excretion of cadmium in urine and greater accumulation of cadmium in kidney were observed in the diabetic group, and this may be one of the mechanisms underlying the susceptibility of diabetic animals to the effects of cadmium. Further biochemical and histological studies are required in order to explain the detailed events involved in inducing such changes in the toxicokinetics of cadmium.
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PMID:The susceptibility to nephrotoxicity of streptozotocin-induced diabetic rats subchronically exposed to cadmium chloride in drinking water. 1064 19

Cadmium (Cd) and arsenic (As) are important inorganic toxicants in the environment. Humans certainly have the potential to be exposed to the mixtures of Cd and As, but the toxicological interactions of these inorganic mixtures are poorly defined. Metallothionein (MT) is a cysteine-rich, metal-binding protein that plays an important role in Cd detoxication, but its role in As toxicity is less certain. To examine the role of MT in Cd- and/or As-induced nephrotoxicity, MT-I/II-knockout (MT-null) mice and background-matched wild-type (WT) mice were fed CdCl(2) (100 ppm Cd) in the diet, NaAsO(2) (22.5 ppm As) in the drinking water, or Cd plus As for 4 months. Subsequently, nephrotoxicity was examined by morphological and biochemical techniques. Chronic exposure to Cd produced more renal toxicity than As, and the combination of Cd and As produced even more renal injury than caused by either of the chemicals given alone. In mice receiving Cd plus As, proximal tubule degeneration and atrophy, glomerular swelling and interstitial fibrosis were more severe than those produced by either inorganic. Furthermore, lack of MT rendered MT-null mice more sensitive than WT mice to the nephrotoxicity produced by chronic Cd- and/or As-exposure. MT-null mice were especially susceptible to the toxicity produced by the combination of Cd and As, as evidenced by decreased body weight, enzymuria, glucosuria, proteinuria and nephropathy. In conclusion, this study indicates that As may potentiate Cd nephrotoxicity during the long-term, combined exposure, and that intracellular MT plays a role in decreasing the nephropathy of combined exposure to Cd and As.
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PMID:Chronic combined exposure to cadmium and arsenic exacerbates nephrotoxicity, particularly in metallothionein-I/II null mice. 1092 98