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, 42.3â€Š±â€Š2.5% (Pâ€ Š<â€Š0.01) and 60. 4â€Š±â€Š15.1% (Pâ€Š <â€Š0.01) 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 (200â€Šmg/kg per day). The pharmacological treatment prevented iron tissue accumulation, as indicated by the increase in renal and hepatic T2 SI of, respectively, 120.0â€Š±â€Š10. 1% (Pâ€Š<â€Š0.01) and 73.9â€Š±â€Š4.4% (Pâ€ Š<â€Š0.01) 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-β 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.
Altered iron homeostasis in an animal model of hypertensive nephropathy : stroke-prone rats / P. Gelosa, A. Pignieri, E. Gianazza, S. Criniti, U. Guerrini, M.D. Cappellini, C. Banfi, E. Tremoli, L. Sironi. - In: JOURNAL OF HYPERTENSION. - ISSN 0263-6352. - 31:11(2013 Sep 11), pp. 2259-2269.
|Titolo:||Altered iron homeostasis in an animal model of hypertensive nephropathy : stroke-prone rats|
GELOSA, PAOLO (Primo)
PIGNIERI, ALICE (Secondo)
TREMOLI, ELENA (Penultimo)
SIRONI, LUIGI (Ultimo)
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||11-set-2013|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1097/HJH.0b013e3283642f3e|
|Appare nelle tipologie:||01 - Articolo su periodico|