Toxicokinetic characteristics and effects of diphenylarsinic acid on dopamine in the striatum of free-moving mice

Abstract

Diphenylarsinic acid (DPAA), an artificial phenyl arsenic compound, is considered a groundwater pollutant in Japan. Previous human and animal studies suggested that DPAA affects the central nervous system; however, these effects are poorly understood. The present study investigated the toxicokinetic characteristics and effects of DPAA on dopamine (DA) in the striatum of free-moving mice after a single oral administration. In a simultaneous blood and brain microdialysis study, only DPAA was detectable in both blood and striatum dialysate samples immediately after DPAA administration. DPAA concentrations in the striatum and blood dialysate rapidly reached a maximum, then decreased over time in an essentially parallel manner. A more detailed brain microdialysis examination of intracerebral kinetics revealed that the concentration of DPAA in the striatum dialysate began to increase within 15 min, reaching a maximum approximately 1 h after administration, and then decreased with a biological half-life of approximately 2 h. Moreover, a single oral administration of DPAA at 0.5-32 mg/kg affected the extracellular DA level in the striatum. The effect on DA level changed slowly after DPAA administration, with a bell-shaped dose-response relationship. The present study suggests that DPAA is rapidly absorbed into the blood circulating in the gastrointestinal tract and passes through the blood-brain barrier to subsequently affect DA levels in the striatum in mice after a single oral administration.

Keywords: Blood brain barrier; Microdialysis; Nigrostriatal dopaminergic system; Organoarsenical; Toxicodynamics; Toxicokinetics.