Related Experiment Video
Updated: Feb 22, 2026
Live-cell Imaging of Lysosomal Membrane Permeabilization During Necroptosis
Published on: November 14, 2025
Necroptosis as a potential therapeutic target in multiple organ dysfunction syndrome
Yao-Li Cui1,2, Li-Hua Qiu1, Shi-Yong Zhou1
1Department of Lymphoma, Tianjin's Clinical Research Center for Cancer and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.
Purpose:
To investigate how necroptosisis, i.e. programmed necrosis, is involved in MODS, and to examine whether Nec-1, a specific necroptosis inhibitor, ameliorates multiorgan injury in MODS.
Experimental Design:
A model of MODS was established in six-week old SD rats using fracture trauma followed by hemorrhage. Control animals received sham surgery. Cell death form and necrosome formation were measured by fluorescence-activated cell sorting and western blotting. MODS rats were randomly assigned to receive Nec-1 or saline with pretreatment and once daily. The first end-point was 72 hours survival. Organ injury and dysfunction, inflammatory cytokine levels, and necroptotic execution protein expression were also recorded.
Results:
Organ injury and dysfunction were significantly more severe in the MODS group than the sham group (all p<0.01). Furthermore, MODS-induced liver, lung and kidney tissue injury was characterized by necroptosis rather than apoptosis, and accompanied by necrosome formation. Compared to MODS group, Nec-1 administration significantly improved 72 hours survival (p<0.01). Nec-1 administration significantly reduced necroptosis-induced liver, lung and kidney injury and dysfunction, inhibited inflammatory cytokines production, inhibited release of necroptotic execution proteins such as high-mobility group box 1 and mixed-lineage kinase domain-like protein pseudokinase in MODS rats (all p<0.01).
Conclusions:
These results suggest that necroptosis is involved the pathology of MODS. Further, a necroptotic inhibitor Nec-1 may be considered as an adjunct treatment for MODS.
Insights
Necroptosis, a form of programmed necrosis, significantly contributes to multiple organ dysfunction syndrome (MODS). Necrostatin-1 (Nec-1) treatment effectively reduced organ injury and improved survival in a rat MODS model.
Area of Science:
- Cell Biology
- Immunology
- Pathology
Background:
- Multiple organ dysfunction syndrome (MODS) is a critical condition with high mortality.
- The precise mechanisms underlying MODS pathogenesis, particularly cell death pathways, require further elucidation.
Purpose of the Study:
- To investigate the role of necroptosis (programmed necrosis) in MODS.
- To evaluate the therapeutic potential of Necrostatin-1 (Nec-1), a specific necroptosis inhibitor, in ameliorating multiorgan injury in MODS.
Main Methods:
- Established a rat model of MODS using fracture trauma and hemorrhage.
- Assessed cell death, necrosome formation, organ injury, and inflammatory markers.
- Administered Nec-1 or saline to MODS rats and monitored 72-hour survival.
Main Results:
- MODS rats exhibited severe organ injury and dysfunction compared to controls.
- MODS-induced liver, lung, and kidney injury were primarily characterized by necroptosis.
- Nec-1 treatment significantly improved survival, reduced organ damage, and suppressed inflammatory responses in MODS rats.
Conclusions:
- Necroptosis plays a critical role in the pathological processes of MODS.
- Nec-1 demonstrates therapeutic potential as an adjunct treatment for MODS.
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