Elimination of plasma phosphatidylcholine hydroperoxide by a seleno-organic compound, Ebselen.
The effects of a seleno-organic compound, Ebselen [2-phenyl-1,2-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 phosphatidylcholine 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 microM Ebselen, respectively. In human plasma, 79, 87, and 86% of PCOOH was eliminated after the incubation with 1, 10, and 100 microM Ebselen, respectively. In an in vivo study 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 4 h 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.
Miyazawa
T
T
Department of Applied Biological Chemistry, Tohoku University, Sendai.
Suzuki
T
T
Fujimoto
K
K
Kinoshita
M
M
D000818:Animals; D001393:Azoles / Q000008:administration & dosage / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D054833:Isoindoles; D007700:Kinetics; D008081:Liposomes / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000097:blood* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D001393:Azoles; D054833:Isoindoles; D008081:Liposomes; D016566:Organoselenium Compounds; D010713:Phosphatidylcholines; C057590:phosphatidylcholine hydroperoxide; C042986:ebselen