RGD Reference Report - Altered iron homeostasis in an animal model of hypertensive nephropathy: stroke-prone rats. - Rat Genome Database

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Altered iron homeostasis in an animal model of hypertensive nephropathy: stroke-prone rats.

Authors: Gelosa, P  Pignieri, A  Gianazza, E  Criniti, S  Guerrini, U  Cappellini, MD  Banfi, C  Tremoli, E  Sironi, L 
Citation: Gelosa P, etal., J Hypertens. 2013 Nov;31(11):2259-69. doi: 10.1097/HJH.0b013e3283642f3e.
RGD ID: 11041817
Pubmed: PMID:24029866   (View Abstract at PubMed)
DOI: DOI:10.1097/HJH.0b013e3283642f3e   (Journal Full-text)

BACKGROUND AND AIM: Iron is the most abundant metal in mammalian cells, and plays a pivotal role in many metabolic processes. Dysregulated iron homeostasis is involved in the cause of a number of pathological processes including renal diseases. METHODS AND RESULTS: Longitudinal MRI scans of salt-loaded spontaneously hypertensive stroke-prone rats (SHRSP), an animal model that spontaneously develops hypertensive nephropathy, showed a decrease in renal and hepatic T2 SI (a sign of iron accumulation) of, respectively, 42.3 +/- 2.5% (P < 0.01) and 60.4 +/- 15.1% (P < 0.01) in comparison with SHRSP fed a standard diet. This was accompanied by the development of renal inflammation and oxidative stress (as evaluated by immunohistochemical and proteomic analyses), mitochondrial dysfunction, massive proteinuria and sustained intravascular hemolysis with the subsequent depletion of plasma haptoglobin, which was responsible for the renal uptake of hemoglobin and iron accumulation. In order to investigate the role of iron in these pathological processes, we subcutaneously treated the salt-loaded rats with the iron chelator deferoxamine (200 mg/kg per day). The pharmacological treatment prevented iron tissue accumulation, as indicated by the increase in renal and hepatic T2 SI of, respectively, 120.0 +/- 10.1% (P < 0.01) and 73.9 +/- 4.4% (P < 0.01) in comparison with salt-loaded rats treated with vehicle alone. Deferoxamine also preserved renal morphology and function, the renal infiltration of ED-1-positive macrophages/monocytes, and the expression of MCP-1 and TGF-beta mRNA, reduced the level of reactive oxygen species, and improved the activity of mitochondrial cytochrome c oxidase. CONCLUSION: These findings suggest that iron dysmetabolism is involved in the development of hypertensive nephropathy in SHRSP.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hypertensive Nephropathy treatmentISOHp (Rattus norvegicus)11041817; 11041817 RGD 
Hypertensive Nephropathy treatmentIEP 11041817 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hp  (haptoglobin)

Genes (Mus musculus)
Hp  (haptoglobin)

Genes (Homo sapiens)
HP  (haptoglobin)

Additional Information