Near-infrared chemiluminescence imaging of superoxide anion production in kidneys with iron3+-nitrilotriacetate-induced acute renal oxidative stress in rats.

Abstract

Iron-catalyzed oxidative stress generates reactive oxygen species in the kidney and induces oxidative damage including lipid, protein, and DNA modifications which induces renal injury and may lead to cancer. An analysis of oxidative stress dynamics by reactive oxygen species has not been performed non-invasively in real time in intact kidneys and is a significant challenge in biology and medicine. Here, I report that MCLA-800 is a near-infrared chemiluminescent probe that visualizes the dynamics of superoxide anion (O2•-) production and the upstream generation of reactive oxygen species in living rat kidneys suffering acute renal oxidative stress induced by intraperitoneal administration of iron3+-nitrilotriacetate (Fe3+-NTA) as a representative Fe3+ chelate. MCLA-800 was intravenously injected at 250nmol/kg body weight and immediately transported to the kidneys with the emitting light dependent on O2•- production. The magnitude of O2•- production correlated with the Fe3+-NTA dose. O2•- was continuously produced in the blood stream following Fe3+-NTA injection at 0.15mmol/kg body weight, while peak production in the renal cortex occurred at 24h, then decreased to the background level at 72h. This study clearly revealed the dynamics of Fe3+-NTA-mediated O2•- production in the living kidney by chemiluminescent imaging of O2•- production using MCLA-800.