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Prophylactic Effect of Recombinant Human Soluble Thrombomodulin for Hepatic Sinusoidal Obstruction Syndrome Model
Shunsuke Kanou1, Tomoharu Miyashita2, Yasuhiko Yamamoto3
1Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
Aim:
The present study aimed to examine the effects of prophylactic administration of recombinant human soluble thrombomodulin (rTM) for the prevention of sinusoidal obstruction syndrome (SOS).
Materials And Methods:
Crl:CD1 mice were allocated to the rTM, placebo, and control groups. The rTM group received an intraperitoneal administration of rTM, with intraperitoneal administration of monocrotaline (MCT) 1 h later. The placebo group received PBS instead of rTM, and the control group received PBS instead of rTM and MCT. Mice were sacrificed 48 h after MCT administration, and blood and liver tissues were evaluated. Immunostaining was performed using anti-CD42b and anti-SE-1 antibodies, and AZAN staining. Levels of plasminogen activator inhibitor (PAI-1) and endothelial nitric oxide synthase (eNOS) in whole liver tissues were estimated using RT-PCR.
Results:
Hematoxylin-eosin staining showed that SOS-related findings were markedly attenuated in the rTM group compared to the placebo group. CD42b immunostaining showed the presence of extravasated platelet activation (EPA) in the Disse space in the placebo group, but this was less noticeable in the rTM group. PAI-1 levels were significantly lower in the rTM group than in the placebo group in RT-PCR. However, eNOS levels were significantly higher in the rTM group than in the placebo group.
Conclusion:
Administration of rTM may prevent SOS by protecting sinusoidal endothelial cells.
Insights
Recombinant human soluble thrombomodulin (rTM) may prevent sinusoidal obstruction syndrome (SOS) by protecting liver cells. This study found rTM attenuated SOS findings and reduced platelet activation in mice.
Area of Science:
- Hepatology
- Pharmacology
- Vascular Biology
Background:
- Sinusoidal obstruction syndrome (SOS) is a serious complication following hematopoietic stem cell transplantation.
- Current treatments for SOS are limited, necessitating the exploration of novel prophylactic strategies.
Purpose of the Study:
- To investigate the efficacy of prophylactic administration of recombinant human soluble thrombomodulin (rTM) in preventing SOS.
- To evaluate the protective effects of rTM on sinusoidal endothelial cells.
Main Methods:
- Crl:CD1 mice were divided into rTM, placebo, and control groups.
- Mice received rTM or placebo followed by monocrotaline (MCT) to induce SOS.
- Liver tissues and blood were analyzed using histological staining and RT-PCR for key markers.
Main Results:
- rTM administration significantly attenuated SOS-related histological findings compared to placebo.
- Extravasated platelet activation in the Disse space was reduced in the rTM group.
- rTM treatment led to lower plasminogen activator inhibitor (PAI-1) and higher endothelial nitric oxide synthase (eNOS) levels.
Conclusions:
- Prophylactic administration of rTM demonstrates potential in preventing SOS.
- rTM appears to protect sinusoidal endothelial cells, thereby mitigating SOS development.
