Background and Purpose - Oxidative stress plays a pivotal role in the pathogenesis of renal and cerebrovascular injury in salt-loaded stroke-prone spontaneously hypertensive rat (SHRSP)1,2. Our preliminary data showed an iron accumulation in the kidney of SHRSP before stroke appearance. Thus, the aim of the study was to characterize by magnetic resonance imaging (MRI) the renal iron deposition in a longitudinally in vivo study and to determine the role of iron on the pathological events occurring in SHRSP. Methods and Results - SHRSP fed a high-salt diet were treated subcutaneously with vehicle or 200 mg/kg/day of deferoxamina (DFO) an iron chelator. The vehicle-treated rats developed hypertension, stroke, proteinuria and kidney morphological alterations. Renal iron accumulation visualized by MRI using a gradient echo sequence was detected after established proteinuria and before stroke appearance. Iron histological staining (Perls’) correlated with the T2* MR signal intensity (MRSI) data, indicating that the signal reduction in the MR images was due to the presence of iron. Interestingly, MRSI of the renal cortex was found to decrease with the progression of kidney disease. Vehicle-treated SHRSP showed decreased haematocrit, serum haptoglobin depletion and haematological alterations, suggesting an involvement of hemolytic process in the renal iron accumulation. Control animals developed systemic oxidative stress and renal mitochondrial dysfunction. DFO treatment delayed stroke appearance, prevented renal iron accumulation and preserved renal physiology and morphology. These beneficial effects seems mainly to be related to the ability of DFO to reduce free-iron derived from hemolysis and to its anti-oxidant proprieties. Conclusions - We found, in this longitudinally in vivo study, that kidney T2* could be considered as a biomarker for renal iron accumulation. Our data, for the first time, support the involvement of iron in the development of renal and brain damage in salt-loaded SHRSP

Renal iron deposition and stroke : a longitudinal MRI study in SHRSP / A. Pignieri, P. Gelosa, U. Guerrini, E. Tremoli, L. Sironi. ((Intervento presentato al convegno Next Step : la giovane ricerca avanza tenutosi a Milano nel 2010.

Renal iron deposition and stroke : a longitudinal MRI study in SHRSP

A. Pignieri;P. Gelosa;U. Guerrini;E. Tremoli;L. Sironi
2010-07-01

Abstract

Background and Purpose - Oxidative stress plays a pivotal role in the pathogenesis of renal and cerebrovascular injury in salt-loaded stroke-prone spontaneously hypertensive rat (SHRSP)1,2. Our preliminary data showed an iron accumulation in the kidney of SHRSP before stroke appearance. Thus, the aim of the study was to characterize by magnetic resonance imaging (MRI) the renal iron deposition in a longitudinally in vivo study and to determine the role of iron on the pathological events occurring in SHRSP. Methods and Results - SHRSP fed a high-salt diet were treated subcutaneously with vehicle or 200 mg/kg/day of deferoxamina (DFO) an iron chelator. The vehicle-treated rats developed hypertension, stroke, proteinuria and kidney morphological alterations. Renal iron accumulation visualized by MRI using a gradient echo sequence was detected after established proteinuria and before stroke appearance. Iron histological staining (Perls’) correlated with the T2* MR signal intensity (MRSI) data, indicating that the signal reduction in the MR images was due to the presence of iron. Interestingly, MRSI of the renal cortex was found to decrease with the progression of kidney disease. Vehicle-treated SHRSP showed decreased haematocrit, serum haptoglobin depletion and haematological alterations, suggesting an involvement of hemolytic process in the renal iron accumulation. Control animals developed systemic oxidative stress and renal mitochondrial dysfunction. DFO treatment delayed stroke appearance, prevented renal iron accumulation and preserved renal physiology and morphology. These beneficial effects seems mainly to be related to the ability of DFO to reduce free-iron derived from hemolysis and to its anti-oxidant proprieties. Conclusions - We found, in this longitudinally in vivo study, that kidney T2* could be considered as a biomarker for renal iron accumulation. Our data, for the first time, support the involvement of iron in the development of renal and brain damage in salt-loaded SHRSP
SHRSP ; kidney ; iron ; oxidative stress ; deferoxamine
Settore BIO/14 - Farmacologia
Centro di Ricerche Farmacologiche per lo Studio e la Prevenzione delle Malattie Cardiovascolari CRF
Renal iron deposition and stroke : a longitudinal MRI study in SHRSP / A. Pignieri, P. Gelosa, U. Guerrini, E. Tremoli, L. Sironi. ((Intervento presentato al convegno Next Step : la giovane ricerca avanza tenutosi a Milano nel 2010.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/167601
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