Journal Article Kinetics and metabolism of apocynin in the mouse brain assessed with positron-emission tomography

Okamura, Toshimitsu  ,  Okada, Maki  ,  Kikuchi, Tatsuya  ,  Wakizaka, Hidekatsu  ,  Ming-Rong, Zhang

38pp.84 - 89 , 2018-01 , ELSEVIER
Background: Apocynin is a constituent of the medicinal herb Picrorhiza kurroa. It is an inhibitor of nicotinamideadenine dinucleotide phosphate oxidase. This compound shows potential anti-inflammatory and antioxidanteffects and has been tested as a neuroprotectant in many animal models of brain disease. In such studies, understandingthe brain kinetics of apocynin would be important for interpreting its in vivo efficacy; however, littlehas been reported on the kinetics of apocynin in the brain.Purpose: The purpose of this study is to investigate the kinetics and metabolism of apocynin in the brain of mice.Study design: The kinetics and metabolism of apocynin were examined using [11C]apocynin and positronemissiontomography (PET).Methods: In vivo PET scanning was performed in mice for 20 min after intraperitoneal administration of anapocynin solution containing [11C]apocynin. Metabolites in the brain were analyzed using high-performanceliquid chromatography. The doses of apocynin used ranged from <1.5 μg/kg (tracer dose) to 100 mg/kg.Results: Brain radioactivity during the period of 0 to 20 min after administration was negligible at the tracer doseand extremely low at the dose of 10 mg/kg. Moderate radioactivity was observed in the brain a few minutes afteradministration at the doses of 25 and 50 mg/kg and rapidly decreased thereafter. At a dose of 100 mg/kg, [11C]apocynin resulted in a high uptake of radioactivity followed by a gradual washout. In contrast to the brain, aclear dose-dependent increase in radioactivity was not observed in the blood. The fraction of the unchangedform in the brain decreased with time, and the degree of the reduction depended on apocynin doses: apocyninwas rapidly metabolized in the brain at lower doses, whereas it was slowly decomposed at higher doses. On thebasis of these data, the maximum apocynin concentrations in the brain were calculated to be 10 μM (10 mg/kg),49 μM (25 mg/kg), 150 μM (50 mg/kg), and 380 μM (100 mg/kg). A metabolite observed in the brain was foundto be apocynin glucuronide but not diapocynin, an active metabolite.Conclusion: These results would be useful for an evaluation of the potential efficacy of apocynin as a neuroprotectiveagent.

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