Subject: iron/Japanese/kidney damage
Since 1983, researchers have warned us to avoid supplements that
contain iron may be a primary cause of free radical induced
degenerative disease. In a study in the March 29,1994 issue of the
Proceedings of the National Academy of Sciences, Japanese researchers
found that iron caused tubular necrosis (kidney damage), leading to a
high incidence of renal adenocarcinoma (kidney cancer).
This is not an isolated study - just another of the multitude of
studies showing that iron is a cause of the diseases that kill us. The
FDA requires that food companies fortify many products with iron,
which causes most Americans to get too much iron from their diet.
Subject: kidney/iron/renal
Title: The role of tubular iron accumulation in the remnant kidney.
Author(s): Nankivell BJ; Chen J; Boadle RA; Harris DC
Address: Department of Renal Medicine, Westmead Hospital, Sydney,
Australia.
Source: J Am Soc Nephrol 1994 Feb;4(8):1598-607
Abstract: Iron has been implicated in the pathophysiology of several
models of acute and chronic renal disease. In this study,
energy-dispersive x-ray spectrometry was used to quantify and localize
iron in rat remnant kidneys (RK) and normal kidneys (NK) and to
determine its pathophysiologic significance. Substantial iron
accumulation occurred in proximal tubular cell secondary lysosomes of
RK (P 0.001 versus NK) and reached a plateau at 8 wk after partial
nephrectomy. In NK, minor increases of iron also occurred with aging
(P 0.02). Proximal tubular iron accumulation correlated independently
with protein excretion (r = 0.90) and impairment of GFR (r = 0.70) and
was associated with tubular damage and phosphate accumulation (both P
0.001). Iron nitrilotriacetate (1 mg/kg ip) increased tubular
lysosomal iron accumulation and tubular damage (P 0.001 versus
nitrilotriacetate) in NK, comparable to levels seen in untreated RK,
and increased cortical cytosolic malondialdehyde, consistent with
reactive oxygen species generation. The iron chelator deferoxamine (30
mg/kg per day ip) significantly reduced iron accumulation and tubular
damage in RK at 4 wk, compared with deferoxamine chelated to iron and
untreated RK. These results suggest that filtered iron enters the
remnant tubular lysosomes across the brush border membrane by
endocytosis and may produce tubular damage in chronic renal disease by
the generation of reactive oxygen species
Major Indexes:
* Iron [metabolism]
* Kidney Failure, Chronic [metabolism]
* Kidney [chemistry]
Minor Indexes:
* Creatinine [metabolism]
* Deferoxamine [therapeutic use]
* Disease Models, Animal
* Electron Probe Microanalysis
* Ferric Compounds [toxicity]
* Infarction [metabolism]
* Iron [toxicity]
* Kidney Failure, Chronic [pathology]
* Kidney Tubules, Proximal [chemistry] [drug effects]
[ultrastructure]
* Kidney [blood supply]
* Lysosomes [metabolism] [ultrastructure]
* Microscopy, Electron
* Nephrectomy [adverse effects]
* Nitrilotriacetic Acid [analogs & derivatives] [toxicity]
* Proteinuria [etiology]
* Rats, Wistar
* Rats
* Reactive Oxygen Species
* Transferrin [urine]
Reagent Names:
* 0 (Ferric Compounds)
* 0 (Reactive Oxygen Species)
* 11096-37-0 (Transferrin)
* 139-13-9 (Nitrilotriacetic Acid)
* 16448-54-7 (ferric nitrilotriacetate)
* 60-27-5 (Creatinine)
* 70-51-9 (Deferoxamine)
* 7439-89-6 (Iron)
Language: English
Periodical Type: JOURNAL ARTICLE
Subject: kidney/iron
Lab Invest 2000 Dec;80(12):1905-14
Association of renal injury with increased oxygen free radical activity and
altered nitric oxide metabolism in chronic experimental hemosiderosis.
Zhou XJ, Laszik Z, Wang XQ, Silva FG, Vaziri ND
Department of Pathology, University of Texas Southwestern Medical
Center, Dallas 75390-9073, USA. joseph.zhou@utsouthwestern.edu
[Medline record in process]
Chronic iron (Fe) overload is associated with a marked increase in
renal tissue iron content and injury. It is estimated that 10% of the
American population carry the gene for hemochromatosis and 1% actually
suffer from iron overload. The mechanism of iron overload-associated
renal damage has not been fully elucidated. Iron can accelerate lipid
peroxidation leading to organelle membrane dysfunction and subsequent
cell injury/death. Iron-catalyzed generation of reactive oxygen
species (ROS) is responsible for initiating the peroxidatic reaction.
We investigated the possible association of oxidative stress and its
impact on nitric oxide (NO) metabolism in iron-overload-associated
renal injury. Rats were randomized into Fe-loaded (given 0.5 g
elemental iron/kg body weight as iron dextran; i.v.), Fe-depleted
(given an iron-free diet for 20 weeks), and control groups. Renal
histology, tissue expression of endothelial and inducible nitric oxide
synthases (eNOS and iNOS), renal tissue expression of nitrotyrosine,
plasma, and renal tissue lipid peroxidation product, malondialdehyde
(MDA), and plasma and urinary NO metabolites (NOx) were examined. Iron
overload was associated with mild proteinuria, tissue iron deposition
together with significant glomerulosclerosis, tubular atrophy, and
interstitial fibrosis. Rare focal glomerulosclerosis and
tubulointerstitial changes were noted in normal controls. No renal
lesions were observed in Fe-depleted rats. Iron deposits were seen in
glomeruli, proximal tubules, and interstitium. The iron staining in
the distal tubules was negligible. Both plasma and renal tissue MDA
and renal tissue nitrotyrosine were increased significantly in
Fe-loaded rats compared with control rats. In contrast, Fe-depleted
animals showed a marked reduction in plasma and renal tissue MDA and
nitrotyrosine together with significant elevation of urinary NOx
excretion. In addition, iron-overload was associated with
up-regulation of renal eNOS and iNOS expressions when compared with
the control and Fe-depleted rats that showed comparable values. In
conclusion, chronic iron overload resulted in iron deposition in the
glomeruli and proximal tubules with various renal lesions and evidence
of increased ROS activity, enhanced ROS-mediated inactivation, and
sequestration of NO and compensatory up-regulation of renal eNOS and
iNOS expressions. However, iron depletion was associated with reduced
MDA and tissue nitrotyrosine abundance, increased urinary NOx
excretion, normal nitric oxide synthase (NOS) expression, and absence
of renal injury. These findings point to the possible role of ROS in
chronic iron overload-induced renal injury.
PMID: 11140702, UI: 21020974
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Subject: kidney/iron
Lab Invest 2000 Dec;80(12):1905-14
Association of renal injury with increased oxygen free radical activity and
altered nitric oxide metabolism in chronic experimental hemosiderosis.
Zhou XJ, Laszik Z, Wang XQ, Silva FG, Vaziri ND
Department of Pathology, University of Texas Southwestern Medical
Center, Dallas 75390-9073, USA. joseph.zhou@utsouthwestern.edu
[Medline record in process]
Chronic iron (Fe) overload is associated with a marked increase in
renal tissue iron content and injury. It is estimated that 10% of the
American population carry the gene for hemochromatosis and 1% actually
suffer from iron overload. The mechanism of iron overload-associated
renal damage has not been fully elucidated. Iron can accelerate lipid
peroxidation leading to organelle membrane dysfunction and subsequent
cell injury/death. Iron-catalyzed generation of reactive oxygen
species (ROS) is responsible for ini(HOME) tiating the peroxidatic reaction.
We investigated the possible association of oxidative stress and its
impact on nitric oxide (NO) metabolism in iron-overload-associated
renal injury. Rats were randomized into Fe-loaded (given 0.5 g
elemental iron/kg body weight as iron dextran; i.v.), Fe-depleted
(given an iron-free diet for 20 weeks), and control groups. Renal
histology, tissue expression of endothelial and inducible nitric oxide
synthases (eNOS and iNOS), renal tissue expression of nitrotyrosine,
plasma, and renal tissue lipid peroxidation product, malondialdehyde
(MDA), and plasma and urinary NO metabolites (NOx) were examined. Iron
overload was associated with mild proteinuria, tissue iron deposition
together with significant glomerulosclerosis, tubular atrophy, and
interstitial fibrosis. Rare focal glomerulosclerosis and
tubulointerstitial changes were noted in normal controls. No renal
lesions were observed in Fe-depleted rats. Iron deposits were seen in
glomeruli, proximal tubules, and interstitium. The iron staining in
the distal tubules was negligible. Both plasma and renal tissue MDA
and renal tissue nitrotyrosine were increased significantly in
Fe-loaded rats compared with control rats. In contrast, Fe-depleted
animals showed a marked reduction in plasma and renal tissue MDA and
nitrotyrosine together with significant elevation of urinary NOx
excretion. In addition, iron-overload was associated with
up-regulation of renal eNOS and iNOS expressions when compared with
the control and Fe-depleted rats that showed comparable values. In
conclusion, chronic iron overload resulted in iron deposition in the
glomeruli and proximal tubules with various renal lesions and evidence
of increased ROS activity, enhanced ROS-mediated inactivation, and
sequestration of NO and compensatory up-regulation of renal eNOS and
iNOS expressions. However, iron depletion was associated with reduced
MDA and tissue nitrotyrosine abundance, increased urinary NOx
excretion, normal nitric oxide synthase (NOS) expression, and absence
of renal injury. These findings point to the possible role of ROS in
chronic iron overload-induced renal injury.
PMID: 11140702, UI: 21020974
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Subject: iron/transport/explanation/kidney
Kidney Int 1999 Mar;55 Suppl 69:S2-11
Cellular iron metabolism.
Ponka P
Lady Davis Institute for Medical Research, Jewish General Hospital,
Montreal, Quebec, Canada. mdpp@musica.mcgill.ca
Iron is essential for oxidation-reduction catalysis and bioenergetics,
but unless appropriately shielded, iron plays a key role in the
formation of toxic oxygen radicals that can attack all biological
molecules. Hence, specialized molecules for the acquisition, transport
(transferrin), and storage (ferritin) of iron in a soluble nontoxic
form have evolved. Delivery of iron to most cells, probably including
those of the kidney, occurs following the binding of transferrin to
transferrin receptors on the cell membrane. The transferrin-receptor
complexes are then internalized by endocytosis, and iron is released
from transferrin by a process involving endosomal acidification.
Cellular iron storage and uptake are coordinately regulated
post-transcriptionally by cytoplasmic factors, iron-regulatory
proteins 1 and 2 (IRP-1 and IRP-2). Under conditions of limited iron
supply, IRP binding to iron-responsive elements (present in 5'
untranslated region of ferritin mRNA and 3' untranslated region of
transferrin receptor mRNA) blocks ferritin mRNA translation and
stabilizes transferrin receptor mRNA. The opposite scenario develops
when iron in the transit pool is plentiful. Moreover, IRP activities/
levels can be affected by various forms of "oxidative stress" and
nitric oxide. The kidney also requires iron for metabolic processes,
and it is likely that iron deficiency or excess can cause disturbed
function of kidney cells. Transferrin receptors are not evenly
distributed throughout the kidney, and there is a
cortical-to-medullary gradient in heme biosynthesis, with greatest
activity in the cortex and least in the medulla. This suggests that
there are unique iron/heme metabolism features in some kidney cells,
but the specific aspects of iron and heme metabolism in the kidney are
yet to be explained.
Publication Types:
* Review
* Review, tutorial
PMID: 10633416, UI: 20099233
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