Imaging of redox-imbalance and oxidative stress in kidney in vivo, induced by dietary cholesterol

Abstract

We used a mitochondria-penetrating nitroxide, mito-TEMPO, as a contrast probe for imaging of kidney dysfunction in mice, based on the redox-imbalance and oxidative stress in the renal tissues. Kidney dysfunction was triggered by hypercholesterolemia. The mice were divided in three groups: (i) on normal diet (ND; control); (ii) on cholesterol diet (CD); (iii) on cholesterol plus cholestyramine diet (CC). CD mice showed increased plasma levels of total cholesterol and non-HDL-cholesterol, as well as increased serum levels of blood urea nitrogen, uric acid and creatinine, compared to ND mice. CC mice showed slightly increased plasma levels of total cholesterol and HDL-cholesterol, but not non-HDL-cholesterol, compared to ND mice. The serum levels of blood urea nitrogen, uric acid and creatinine in CC mice were equal to those in ND mice. The MRI signal of mito-TEMPO in the kidneys 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 of renal tissues; moderate intensity and relatively short life-time in CC mice, which shows the protective effect of lipid-lowering agents against oxidative damage. The data suggest that hypercholesterolemia induces redox-imbalance and oxidative stress in kidneys and this process could be visualized using MRI and mito-TEMPO as a redox-sensitive contrast substance.

Keywords

• hypercholesterolemia
• kidney dysfunction
• redox-imbalance
• oxidative stress
• magnetic resonance imaging
• cyclic nitroxides