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Embolization by sinusoidal lining cells obstructs the microcirculation in rat sinusoidal obstruction syndrome.
Laurie D DeLeve1, Yoshiya Ito, Nancy W Bethea
1Division of Gastrointestinal and Liver Disease and the Research Center for Liver Diseases, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA. deleve@usc.edu
American Journal of Physiology. Gastrointestinal and Liver Physiology
|February 14, 2003
Summary
Glutathione prevents sinusoidal obstruction syndrome (SOS) by protecting liver cells from damage. This study reveals that SOS begins with swollen liver cells, leading to blood flow obstruction, which glutathione administration effectively blocks.
Area of Science:
- Hepatology
- Microcirculation Research
- Toxicology
Background:
- Mechanisms of sinusoidal obstruction syndrome (SOS) and its microcirculatory obstruction remain unclear.
- SOS occurs early in disease, presenting a critical therapeutic target.
- Understanding the initial cellular events is crucial for developing interventions.
Purpose of the Study:
- To elucidate the mechanisms of microcirculatory obstruction in monocrotaline-induced SOS in rats.
- To investigate the protective role of glutathione against SOS development.
- To identify the cellular targets and sequence of events initiating SOS.
Main Methods:
- In vivo microscopy and transmission electron microscopy were used to study rats treated with monocrotaline.
- Rats received continuous intraportal glutathione infusion to assess its therapeutic effect.
- Observations were made at multiple time points (0.5 to 10 days) post-treatment.
Main Results:
- Monocrotaline induced sinusoidal endothelial cell (SEC) swelling within 12 hours, leading to gaps and dissection of the sinusoidal lining.
- Microcirculatory obstruction resulted from emboli of SECs, red blood cells, and monocytes.
- Glutathione infusion prevented SEC swelling and subsequent SOS pathology, preserving sinusoidal integrity.
Conclusions:
- SOS is initiated by damage to sinusoidal endothelial cells (SECs).
- Microcirculatory obstruction involves sinusoidal lining dissection and embolization, exacerbated by monocyte adhesion.
- Glutathione effectively prevents SOS by maintaining the integrity of the sinusoidal barrier.