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)

Both chromate and citrinin have been shown to produce acute renal damage. Although both substrates act on the proximal tubule in the rat, they affect different parts of that nephron segment. As with most nephrotoxicants, the mechanism(s) or subcellular target(s) for citrinin or chromate is unknown. The availability of methodology for isolation of functional membrane vesicles has afforded the opportunity to study the plasma membrane as a target for the effects of citrinin and chromate. Whether studied solely with in vitro conditions or after administration to the rat, chromate exhibited its primary action on the basolateral (BL) membrane vesicles. This was exhibited by a reduction in the p-aminohippurate (PAH) overshoot. At both 3 and 16 hr after treatment (40 mg/kg, sc) there was a significant, but relatively modest, effect on glucose transport by brush border (BB) vesicles. Citrinin, when studied in vitro, inhibited PAH transport (BL vesicles), but had only equivocal effects on BB glucose transport. However, after pretreatment of the rats with citrinin (60 mg/kg, ip), both BL and BB membrane vesicle function was reduced markedly at 3 hr. By 16 hr, an overshoot had returned for both transport substrates, although the glucose overshoot was still significantly below control. These data demonstrate that both citrinin and chromate alter proximal tubular cell membrane function and do so relatively early after administration to the rat. This effect suggests that alteration of membrane function by these nephrotoxicants is an early, if not initiating, event in the production of acute tubular necrosis.
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PMID:The effects of potassium chromate and citrinin on rat renal membrane transport. 188 11

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