Nitroxide-enhanced magnetic resonance imaging of kidney dysfunction in vivo based on redox-imbalance and oxidative stress.

ABSTRACT

This study reports a non-invasive magnetic resonance imaging (MRI) of kidney dysfunction in mice, based on the induction of redox-imbalance and oxidative stress in the renal tissues, using mito-TEMPO as redox-sensitive contrast probe. Kidney dysfunction was triggered by hypercholesterolemia. The mice were divided in three groups (i) on normal diet (ND); (ii) on cholesterol diet (CD); (iii) on cholesterol plus cholestyramine diet (CC). After 15 weeks feeding, the mice were subjected to the following analyses plasma cholesterol levels; serum test for renal functionality; nitroxide-enhanced MRI of tissue redox-status in vivo; histochemical staining of tissue section to visualize renal damage; evaluation of total antioxidant capacity and oxidative stress on isolated tissue specimens. MRI signal of mito-TEMPO in the kidney was characterized by high intensity and long life-time in CD mice, indicating a high oxidative capacity of renal tissues; poor intensity and short life-time in ND mice, indicating a high reducing capacity; moderate intensity and relatively short life-time in CC mice, indicating a protective effect of lipid-lowering drug. The data were confirmed on isolated tissue specimens, using conventional tests. They suggest that hypercholesterolemia induces redox-imbalance in kidney and this process could be visualized using MRI and mito-TEMPO as a redox-sensitive contrast.