3-carbamoyl-2-2-5-5-tetramethyl-1-pyrrolidinyl-n-oxyl and Lupus-Nephritis

Mice that lack the Nrf2 (NF-E2-related factor 2) transcription factor develop a lupus-like autoimmune nephritis. The tissue-reducing activity of Nrf2-deficient mice was evaluated using a combination of real-time EPR imaging and spin probe kinetic analysis. Substantial delay in the spin probe 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (Carbamoyl-PROXYL) disappearance in the liver and kidneys of Nrf2-deficient mice was observed by EPR imaging. The half-life of the spin probe in the upper abdominal area was prolonged in both the Nrf2-deficient mice and in aged mice. The combination of Nrf2 deficiency and aging in female mice resulted in the most prolonged half-life of disappearance, which was four times longer than that of juvenile female mice with a wild-type genotype. These results indicate that the low reducing activity in these organs is brought about by both Nrf2 deficiency and the aging process, and it may play a key role in the onset of autoimmune nephritis. This combination of the EPR imaging and half-life analysis appears to be a very powerful tool in the real-time analysis of reducing activity.

Topics: Animals; Cyclic N-Oxides; Diagnostic Imaging; DNA-Binding Proteins; Down-Regulation; Electron Spin Resonance Spectroscopy; Female; Free Radicals; Half-Life; Kidney; Leucine Zippers; Liver; Lupus Nephritis; Mice; Mice, Inbred ICR; Mice, Knockout; NF-E2-Related Factor 2; Organ Size; Pyrrolidines; Spin Labels; Trans-Activators