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An ESR contrast agent is transported to rat liver through organic anion transporter
Authors:Ichikawa Kazuhiro  Sato Yasuko  Kondo Hiroshi  Utsumi Hideo
Institution:  a Department of Bio-function Analysis, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
Abstract:Carboxy PROXYL is a useful extracellular paramagnetic contrast reagent in electron spin resonance (ESR) and magnetic resonance imaging (MRI). Active transfer of the probe was investigated using an in situ liver model in rats. Carboxy PROXYL, a nitroxyl spin probe, was perfused into in situ liver perfusion system from Wistar rats. Concentration of nitroxyl form of the spin probe in effluent increased gradually after introducing perfusate with the spin probe and reached a plateau. The disappearance of Carboxy PROXYL from the perfusate was 40%, which could not be explained with its partition coefficient. Administration of non-selective inhibitors of organic anion transporters, p-aminohippuric acid and penicillin G, inhibited competitively and in a dose dependent manner the transfer of Carboxy PROXYL into rat liver in situ, resulting in increases of Carboxy PROXYL in the effluent. The results demonstrate that there is an active transfer system of an ESR contrast reagent into in situ rat liver through organic anion transporters.
Keywords:In situ liver perfusion  electron spin resonance spectroscopy  spin probe  rat  organic anion transporter  nitroxyl radical
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