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Effects of polymyxin B-immobilized fiber using a rat cecal ligation and perforation model
Masaaki Ito1, Hajime Kase, Osamu Shimoyama
1Department of General and Gastrointestinal Surgery, Omori Hospital, Toho University School of Medicine, Tokyo, Japan. m.itoh@hotmail.com
Insights
Polymyxin B-immobilized fiber (PMX-F) therapy showed potential in reducing organ dysfunction markers and decreasing kidney cell apoptosis in a rat sepsis model. This suggests PMX-F may be a promising treatment for sepsis-induced organ damage.
Area of Science:
- Sepsis and Organ Dysfunction
- Biomaterial-based Therapies
- Inflammatory Response
Background:
- Sepsis-induced organ dysfunction remains a critical challenge in critical care medicine.
- Polymyxin B-immobilized fiber (PMX-F) is an extracorporeal treatment designed for endotoxin adsorption.
- The precise mechanisms by which PMX-F impacts organ-specific injury and apoptosis are not fully elucidated.
Purpose of the Study:
- To evaluate the efficacy of PMX-F therapy in mitigating organ dysfunction in a rat model of sepsis.
- To investigate the effects of PMX-F on key inflammatory markers and apoptosis in sepsis.
Main Methods:
- Cecal ligation and perforation (CLP) was used to induce peritonitis and sepsis in Sprague-Dawley rats.
- Rats were divided into three groups: PMX-F treatment, sham (non-immobilized fiber), and control (no hemoperfusion).
- Blood cytokine levels (IL-6, IL-10, TNF-alpha, PAI-1), tissue histology, and apoptosis were assessed.
Main Results:
- The PMX-F group exhibited a trend towards reduced blood levels of IL-6 and PAI-1 compared to the sham group.
- Anti-PAI-1 antibody staining was observed in lung tissues of control and sham groups, but less so in the PMX-F group.
- Significantly fewer apoptotic cells were found in the renal tubule cells of the PMX-F treated rats compared to control and sham groups.
Conclusions:
- PMX-F therapy may inhibit plasminogen activator inhibitor-1 (PAI-1) expression in lung tissue during sepsis.
- PMX-F treatment demonstrated a protective effect by decreasing apoptosis in renal tubule cells.
- These findings suggest PMX-F has therapeutic potential in managing sepsis-related organ dysfunction, particularly renal injury.
Abstract:
We evaluated the efficacy of polymyxin B-immobilized fiber (PMX-F) on organ dysfunction using a rat cecal ligation and perforation (CLP) model. Fifteen-week-old Sprague-Dawley rats (n = 21) were divided into three groups. For a PMX group, n = 7, peritonitis was induced by CLP. After 24 hours from CLP, endotoxin adsorption was performed for 1 hour with a PMX-F column. A sham group, n = 7, external circulation was performed with nonimmobilized fiber column. A control group, n = 7, were sacrificed 25 hours after CLP (no hemoperfusion performed). The changes in interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha and plasminogen activator inhibitor (PAI)-1 were measured. The lungs, liver, and kidneys were stained with hematoxylin and eosin and anti-PAI-1 antibodies. Terminal uridine-triphosphate nick-end labeling assay was performed to evaluate apoptosis. The PMX group showed a tendency to decrease in blood levels of IL-6 and PAI-1 compared with the sham group. Anti-PAI-1 antibody staining was seen in the lungs of the control and sham groups. The PMX group showed significantly decreased apoptotic cells in renal tubule cells compared with sham and control groups. We conclude that PMX-F may have inhibited PAI-1 expression in the lungs and decreased apoptosis of renal tubule cells.

