Quercetin, a natural flavonoid, protects against hepatic ischemia–reperfusion injury via inhibiting Caspase-8/ASC dependent macrophage pyroptosis

Journal of Advanced Research, Год журнала: 2024, Номер unknown

Опубликована: Май 1, 2024

Hepatic ischemia–reperfusion injury (IRI) is an inevitable adverse event following liver surgery, leading to damage and potential organ failure. Despite advancements, effective interventions for hepatic IRI remain elusive, posing a significant clinical challenge. The innate immune response significantly contributes the pathogenesis of by promoting inflammatory cytotoxic cycle. We have reported that blocking GSDMD-induced pyroptosis in immunity cells protected from injury. However, search inhibitors continues. This study aims evaluate whether quercetin, natural flavonoid, can inhibit mitigate IRI. established murine model cellular efficacy quercetin. Quercetin effectively alleviated IRI-induced tissue necrosis inflammation. found during IRI, cleavage GSDMD occurred macrophages, but not other non-parenchymal cells. inhibited macrophages. Moreover, we quercetin blocked ASC assembly formation NLRP3 inflammasomes AIM2 inflammasomes, suppressing macrophage pyroptosis. Co-immunoprecipitation experiments confirmed interaction between Caspase-8, which mechanism complex inflammasome formation. Overexpression Caspase-8 abolished anti-pyroptosis effect signaling. Furthermore, hepatoprotective activity was reduced myelocytic GSDMD-deficient mice. Our findings suggest has beneficial effects on could attenuate target inhibition via Caspase-8/ASC interaction. recommend might serve as targeted approach prevention personalized treatment perioperative patients.

Язык: Английский

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Hepatic Nonparenchymal Cells and Liver-Associated Lymphoid Cells

Elsevier eBooks, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Caveolin-1 Deficiency in Macrophages Alleviates Carbon Tetra-Chloride-Induced Acute Liver Injury in Mice

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(10), С. 4903 - 4903

Опубликована: Май 20, 2025

Bone marrow-derived macrophages (BMMs) exhibit dynamic behavior and functional capabilities in response to specific microenvironmental stimuli. Recent investigations have proved that BMMs play crucial roles promoting necrotic lesion resolution. Despite substantial advancements understanding their activation interaction with injured livers, researchers face challenges develop effective treatments based on manipulating function. Caveolin-1 (Cav-1) is the major structural protein plasma membrane. We previously reported Cav-1 knockout (KO) mice exhibited less damage necrosis carbon tetrachloride (CCl4)-induced liver injury. hypothesize recruitment of are involved resolution lesions KO mice. Wild-type (WT) were injected CCl4 (10% v/v) induce acute injury model. Blood samples hepatic tissues harvested for serum alanine transaminase (ALT) activity assessment, histopathological examination through hematoxylin–eosin (H&E) staining, subpopulation analysis via flow cytometry. Then, primary isolated cultured investigate effect polarization, migration, STAT3 signal pathway. Validation macrophage depletion was induced by administrating clodronate liposomes (CLs), reconstitution evaluated EGFP labelled BMMs. Following this, depleted CLs, from KO, WT administrated evaluate protective role Cav-1-deleted hepatocellular apoptosis The ratio significantly increased 2.12% (1D), 4.38% (1W), 5.38% (2W) oil control 7.17%, 14.90%, 19.30% CCl4-treated (p < 0.01 or p 0.001). Concurrently, positive a marked elevation 6.41% at 1D 24.90% 2W = 0.0228). exerted effects reducing ALT 26% 0.0265) areas 28% 0.0220) enhancing infiltration 60% 0.0059). In vitro, showed decrease CD206 fluorescence intensity 0.001), time-dependent upregulation arginase-1 mRNA 0.05 0.01), 1.22-fold increase phosphorylated 0.0036), impaired wound healing 12 24 h macrophage-depleting action livers CL injection persists minimum 48 h. Administrated EGFP+ emerged as predominant population following duration liposome-mediated depletion, adoptive transfer demonstrated therapeutic efficacy CCl4-induced injury, reduced 12.8% 0.0105), 25.2% 0.0127), doubled 0.0269), suppressed CXCL9/10 expression 0.0044 0.0385). key attenuates accelerating M2 polarization. may represent potential target

Язык: Английский

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Necrotic Liver Lesion Resolution: Another Mode of Liver Regeneration

Seminars in Liver Disease, Год журнала: 2024, Номер 44(03), С. 333 - 342

Опубликована: Июль 2, 2024

The liver has the great ability to regenerate after partial resection or injury, and mechanisms underlying regeneration have been extensively investigated. Interestingly, acute injuries triggered by various etiologies are associated with formation of necrotic lesions, such lesions also rapidly resolved. However, how repaired not carefully investigated until recently. In this review, we briefly summarize spatiotemporal process lesion resolution in several injury models including immune-mediated drug-induced injury. roles nonparenchymal cells infiltrating immune controlling discussed, which may help identify potential therapies for failure.

Язык: Английский

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Using different zebrafish models to explore liver regeneration

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Окт. 31, 2024

The liver possesses an impressive capability to regenerate following various injuries. Given its profound implications for the treatment of diseases, which afflict millions globally, regeneration stands as a pivotal area digestive organ research. Zebrafish (

Язык: Английский

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