title: Altered iron homeostasis in an animal model of hypertensive nephropathy: stroke-prone rats.
abstract: OBJECTIVE
  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.
  
  
  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-β mRNA, reduced the level of reactive oxygen species, and improved the activity of mitochondrial cytochrome c oxidase.
  
  
  CONCLUSIONS
  These findings suggest that iron dysmetabolism is involved in the development of hypertensive nephropathy in SHRSP.
authors.affiliation: aDipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano bDipartimento di Medicina Interna, Medicina Interna 1A, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano cCentro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gelosa
authors.forename: Alice
authors.initials: A
authors.lastname: Pignieri
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gianazza
authors.forename: Salvatore
authors.initials: S
authors.lastname: Criniti
authors.forename: Uliano
authors.initials: U
authors.lastname: Guerrini
authors.forename: Maria D
authors.initials: MD
authors.lastname: Cappellini
authors.forename: Cristina
authors.initials: C
authors.lastname: Banfi
authors.forename: Elena
authors.initials: E
authors.lastname: Tremoli
authors.forename: Luigi
authors.initials: L
authors.lastname: Sironi
mesh_terms: D000818:Animals; D001794:Blood Pressure; D003676:Deferoxamine / Q000494:pharmacology; D004195:Disease Models, Animal; D006461:Hemolysis / Q000502:physiology; D006706:Homeostasis; D006977:Hypertension, Renal / Q000209:etiology / Q000378:metabolism*; D007501:Iron / Q000378:metabolism* / Q000502:physiology*; D007668:Kidney / Q000503:physiopathology; D008297:Male; D023421:Models, Animal; D009393:Nephritis / Q000209:etiology / Q000378:metabolism*; D018384:Oxidative Stress; D011507:Proteinuria / Q000209:etiology / Q000378:metabolism; D040901:Proteomics; D051381:Rats; D011918:Rats, Inbred SHR; D017382:Reactive Oxygen Species / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000378:metabolism; D020521:Stroke / Q000209:etiology / Q000503:physiopathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D017673:Sodium Chloride, Dietary; D016212:Transforming Growth Factor beta; D007501:Iron; D003676:Deferoxamine