ArticleMediators of inflammation2020
Necrostatin-1 Synergizes the Pan Caspase Inhibitor to Attenuate Lung Injury Induced by Ischemia Reperfusion in Rats.
Article in Mediators of inflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 17 citations in OpenAlex.
- Cell death in ischemia-reperfusion injury: beyond a single-cell-death perspective.Biomarker research · 2026Review
- Melatonin Protects BEAS-2B Cells Against Hypoxia/Reoxygenation-Induced Injury By Reducing MLKL Levels, Suppressing Oxidative Stress and Preserving Mitochondrial Function.Cell biochemistry and function · 2026Article
- Treating acute respiratory distress syndrome with a multifaceted nanomedicine: Inhibition of PANoptosis and enhancement of lung barrier integrity.Materials today. Bio · 2026Article
- The molecular mechanisms and therapeutic implications of PANoptosis in ischemic diseases.Apoptosis : an international journal on programmed cell death · 2025Review
- Primary graft dysfunction after Lung transplantation: unveiling the role of innate immunity.Clinical and experimental immunology · 2025Article
- Cell death in acute lung injury: caspase-regulated apoptosis, pyroptosis, necroptosis, and PANoptosis.Frontiers in pharmacology · 2025Review
- RIPK1 inhibitor ameliorates pulmonary injury by modulating the function of neutrophils and vascular endothelial cells.Cell death discovery · 2024Article
- Advances in lung ischemia/reperfusion injury: unraveling the role of innate immunity.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- Role of Necroptosis in Intervertebral Disc Degeneration.International journal of molecular sciences · 2023Review
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Inhibiting multiple forms of cell death optimizes ganglion cells survival after retinal ischemia reperfusion injury.Cell death & disease · 2022Article
- Blockade of caspase cascade overcomes malaria-associated acute respiratory distress syndrome in mice.Cell death & disease · 2022Article
- The role of necroptosis in common respiratory diseases in children.Frontiers in pediatrics · 2022Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBoth apoptosis and necroptosis have been recognized to be involved in ischemia reperfusion-induced lung injury. We aimed to compare the efficacies of therapies targeting necroptosis and apoptosis and to determine if there is a synergistic effect between the two therapies in reducing lung ischemia reperfusion injury.
methodsForty Sprague-Dawley rats were randomized into 5 groups: sham (SM) group, ischemia reperfusion (IR) group, necrostatin-1+ischemia reperfusion (NI) group, carbobenzoxy-Val-Ala-Asp-fluoromethylketone+ischemia reperfusion (ZI) group, and necrostatin-1+carbobenzoxy-Val-Ala-Asp-fluoromethylketone+ischemia reperfusion (NZ) group. The left lung hilum was exposed without being clamped in rats from the SM group, whereas the rats were subjected to lung ischemia reperfusion by clamping the left lung hilum for 1 hour, followed by reperfusion for 3 hours in the IR group. 1 mg/kg necrostatin-1 (Nec-1: a specific necroptosis inhibitor) and 3 mg/kg carbobenzoxy-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk: a pan caspase inhibitor) were intraperitoneally administrated prior to ischemia in NI and ZI groups, respectively, and the rats received combined administration of Nec-1 and z-VAD-fmk in the NZ group. Upon reperfusion, expressions of receptor-interacting protein 1 (RIP1), receptor-interacting protein 3 (RIP3), and caspase-8 were measured, and the flow cytometry analysis was used to assess the cell death patterns in the lung tissue. Moreover, inflammatory marker levels in the bronchoalveolar lavage fluid and pulmonary edema were evaluated.
resultsBoth Nec-1 and z-VAD-fmk, either alone or in combination, significantly reduced morphological damage, inflammatory markers, and edema in lung tissues following reperfusion, and cotreatment of z-VAD-fmk with Nec-1 produced the optimal effect. The rats treated with Nec-1 had lower levels of inflammatory markers in the bronchoalveolar lavage fluid than those receiving z-VAD-fmk alone (
conclusionsNec-1 synergizes the pan caspase inhibitor to attenuate lung ischemia reperfusion injury in rats. Our data support the potential use of Nec-1 in lung transplantation-related disorders.
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