Inhibitory Effects of Beraprost Sodium in Murine Hepatic Sinusoidal Obstruction Syndrome.

Abstract

In this study, the liver sinusoidal endothelial cells (LSECs)-protective effects of beraprost sodium (BPS) were investigated using mice with monocrotaline (MCT)-induced sinusoidal obstruction syndrome (SOS). The mice were divided into BPS, placebo and control groups. They were killed 48 h after MCT administration, and blood samples and liver tissues were evaluated. Immunostaining was performed using anti-SE-1 and anti-CD42b antibodies, whereas plasminogen activator inhibitor (PAI-1) and endothelial nitric oxide synthase (eNOS) levels were evaluated using western blot or real-time RT-PCR. On pathological examination, SOS-related findings were observed in zone 3 in the placebo group; however, these were significantly suppressed in the BPS group. SE-1 staining showed a consistent number of LSECs in the BPS group compared with that in the placebo group, while CD42b staining showed a significant decrease in the number of extravasated platelet aggregation (EPA) in the BPS group. PAI-1 expression was significantly lower in the BPS group than in the placebo group; however, eNOS expression was significantly higher in the BPS group than in the placebo group. Prophylactic administration of BPS is useful for suppressing the development of SOS through the protective effects of LSEC.