Elimination of plasma phosphatidylcholine hydroperoxide by a seleno-organic compound, ebselen

The effects of a seleno-organic compound, Ebselen [2-phenyl-l, 2-benzoisoselenazol-3(2H)-one], on phospholipid hydroperoxide levels in in vitro and in vivo systems were examined by using high-performance liquid chromatography with chemiluminescence detection (CL-HPLC) as a tool for measuring the hydroperoxide. In in vitro systems, the phos-phatidylcholine hydroperoxide (PCOOH) content in phosphatidylcholine (PC) liposomes was significantly reduced by co-incubation with exogenously added Ebselen; 85, 97, and 99.6% of PCOOH was eliminated with 1, 10, and 100 μM Ebselen, respectively. In human plasma, 79, 87, and 86% of PCOOH was eliminated after the incubation with 1, 10, and 100 μM Ebselen, respectively. In an in vivostudy involving single oral administration of Ebselen (10, 30, and 100 mg/kg rat) to rats, plasma PCOOH (48.8 nM for Ebselen-untreated rat) was significantly decreased to 26.3, 5.6, and 3.3 nM at 2 h after the administration and 6.7, 7.4, and 4.8 nM at 4h after the administration, respectively. These in vivo effects on plasma PCOOH elimination depended on both the dose and the time after the administration. Maximum decrease of plasma PCOOH appeared around 2-4 h after oral administration. The liver and red blood cell PCOOH levels were not affected by oral Ebselen under the present conditions. These findings indicate that the Ebselen may be a potent agent for lowering plasma PCOOH levels in vivo.