Inhibitory Effects of Beraprost Sodium in Murine Hepatic Sinusoidal Obstruction Syndrome

Anticancer Res. 2020 Sep;40(9):5171-5180. doi: 10.21873/anticanres.14520.

Abstract

Background/aim: 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).

Materials and methods: 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.

Results: 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.

Conclusion: Prophylactic administration of BPS is useful for suppressing the development of SOS through the protective effects of LSEC.

Keywords: Beraprost sodium; liver sinusoidal endothelial cells; liver transplantation; oxaliplatin based chemotherapy; sinusoidal obstruction syndrome; veno-occlusive disease.

MeSH terms

  • Animals
  • Biomarkers
  • Biopsy
  • Disease Models, Animal
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Epoprostenol / analogs & derivatives*
  • Epoprostenol / pharmacology
  • Female
  • Hepatic Veno-Occlusive Disease / diagnosis
  • Hepatic Veno-Occlusive Disease / drug therapy*
  • Hepatic Veno-Occlusive Disease / etiology
  • Hepatic Veno-Occlusive Disease / metabolism
  • Immunohistochemistry
  • Liver Transplantation
  • Mice
  • Symptom Assessment
  • Vasodilator Agents / pharmacology*

Substances

  • Biomarkers
  • Vasodilator Agents
  • beraprost
  • Epoprostenol