Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kidney disease is often cited as one of the adverse effects of chromium, yet chronic renal disease due to occupational or environmental exposure to chromium has not yet been reported. Occasional cases of acute tubular necrosis (ATN) following massive absorption of chromate have been described. Chromate-induced ATN has been extensively studied in experimental animals following parenteral administration of large doses of potassium chromate (hexavalent) (15 mg/kg body weight). The chromate is selectively accumulated in the convoluted proximal tubule where necrosis occurs. An adverse long-term effect of low-dose chromium exposure on the kidneys is suggested by reports of low molecular weight (LMW) proteinuria in chromium workers. Excessive urinary excretion of beta 2-microglobulin, a specific proximal tubule brush border protein, and retinol-binding protein has been reported among chrome platers and welders. However, LMW proteinuria occurs after a variety of physiologic stresses, is usually reversible, and cannot by itself be considered evidence of chronic renal disease. Chromate-induced ATN and LMW proteinuria in chromium workers, nevertheless, raise the possibility that low-level, long-term exposure may produce persistent renal injury. The absence of evidence of chromate-induced exposure may produce persistent renal injury. The absence of evidence of chromate-induced chronic renal disease cannot be interpreted as evidence of the absence of such injury. Rather, it must be recognized that no prospective cohort or case-control study of the delayed renal effects of low-level, long-term exposure to chromium has been published.
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PMID:Chromium-induced kidney disease. 193 54

A growing list of drugs, metals, and chemicals has been implicated as the cause of functional and structural damage specifically to the proximal tubular epithelium. Renal biopsies were obtained from three patients who had developed nephrotoxic agent-related acute renal failure. Two of the patients had received gentamicin and viomycin; the third patient had heavy exposure to chromium. All three biopsies showed acute tubular necrosis (ATN) on light microscopy. Electron microscopy revealed that the proximal tubular cells and, to a lesser degree, the distal tubular cells, contained abundant, variably sized myeloid bodies. In our previous experimental study of viomycin-induced ATN in rats, similar ultrastructural findings of a gradual increase in the number of myeloid bodies in the proximal tubular cells were also observed. The constant presence of myeloid bodies in the tubular epithelial cells following drug-induced tubular necrosis suggests that they may represent lysosomal isolation of drug-bound cytoplasmic structures, as a cellular mechanism to degrade toxic substances and, therefore, may serve as an ultrastructural marker of cellular drug uptake and drug disposition.
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PMID:Myeloid bodies in drug-induced acute tubular necrosis. 629 92

In contrast to trivalent chromium (Cr(III)) compounds, hexavalent chromium ((Cr(VI)) compounds are oxidizing agents capable of directly inducing tissue damage and possessing carcinogenic, mutagenic and teratogenic potency. After oral or dermal absorption of Cr(VI), the kidney is the main target organ for chromium accumulation, which might result in acute tubular necrosis in humans. In contrast, an acute toxic effect of Cr(VI) on the liver has not yet been described. Therefore, we used two established epithelial cell lines from the kidney (Opossum kidney cells) and the liver (Hep G2 cells) to design an in vitro-assay which is able to examine acute toxic effects of chromium compounds. Cells of both cell lines were treated with various concentrations of Cr(III) and Cr(VI) ranging from 0.01 micromol/l to 1 mmol/l for 24 h. Thereafter, cell morphology, organization of the intracellular cytoskeleton, number of viable cells and mean cell volume were examined. The results show that Cr(VI), but not Cr(III), has an acute cytotoxic effect and causes a dose-dependent loss in cell viability. The effective dose that caused 50% of cell death was 5 micromol/l for kidney epithelial cells and 50 micromol/l for liver epithelial cells. This means that kidney epithelial cells are 10 times more sensitive towards Cr(VI) treatment than liver epithelial cells and this might explain the known nephrotoxicity in vivo. The loss in cell viability was accompanied by a rounding and detachment of the cells and a marked reduction of intracellular F-actin-containing stress fibers. Microtubules and intermediate-sized filaments were observed to be unaffected. Only in the case of kidney epithelial cells, a dose-dependent cell volume increase was observed after Cr(VI) treatment at concentrations up to 50 micromol/l. At higher concentrations, the cell volume decreased due to the high number of cells undergoing lysis and the appearance of cellular fragments. Various chloride channel blockers with different specificities, molecular structures and inhibitory potentials were tested for their ability to prevent Cr(VI)-induced cell damage. None of the channel blockers was able to inhibit cell damage, suggesting that the uptake of Cr(VI) through the general anion transport system of the cell membrane might be only one facet of cellular uptake and toxification. The data presented here not only confirm the different organ-specific effects of Cr(III) and Cr(VI), but also provide a basis for future experiments on the understanding of acute toxicity of Cr(VI) compounds. Moreover, the results demonstrate that the designed in vitro-assay might be a useful tool to prove whether non-toxic Cr(III) can be oxidized to Cr(VI) under specific industrial conditions (for example, in the leather or chrome industry).
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PMID:Investigations on the nephrotoxicity and hepatotoxicity of trivalent and hexavalent chromium compounds. 982 79

Chromium copper arsenate (CCA) was used for the protection of wood building materials until the restriction by EPA in 2002. During a short period of time 14-24h, a comparative nephrotoxicity study was performed regarding the effects of CCA and its compounds per se. Histopathological and histochemical features were correlated with the concentration of the total arsenic and chromium in mice kidney. Animals were subcutaneously injected with CCA (7.2mg/kg arsenic and 10.2mg/kg chromium per body weight), CrO3 (10.2mg/kg), As2O5 (7.2 mg/kg) and NaCl (0.9%) per se. The histopathological examination of the renal sections evidenced acute tubular necrosis in the groups of animals exposed to CCA (in both periods of time). Although the same contents of pentavalent arsenic and hexavalent chromium were injected in treated animals with CCA and with the prepared solutions of As2O5 and CrO3, the arsenic concentration on kidneys of CCA-exposed animals was much higher than those in animals exposed to As2O5 (32- and 28-fold higher at 14 and 24h, respectively). However, the elimination of chromium seems to occur similarly in the kidneys of animals treated with CCA and CrO(3)per se. Interactions among the components of CCA result in a marked decrease of the ability of kidney to eliminate simultaneously both analytes. The nephrotoxicity of CCA was higher than its components per se, evidencing a possible synergetic effect.
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PMID:Nephrotoxicity effects of the wood preservative chromium copper arsenate on mice: histopathological and quantitative approaches. 1948 32