Dataset Information

Ellagic acid Alleviates hepatic ischemia-reperfusion injury in C57 mice via the Caspase-1-GSDMD pathway.

ABSTRACT:

Background

Ellagic acid (EA) has improving function against oxidative damage and inflammatory reaction in many disorders. Hepatic ischemia-reperfusion injury (IRI) is a common pathophysiological phenomenon in the veterinary clinic. In the present study, the protective effects of EA pretreatment against hepatic IRI-induced injury and the underlying mechanisms were investigated.

Results

We found that pyroptosis is involved in hepatic IRI, which is manifested in increasing the expression of pyroptosis-related genes and promoting the expression of active caspase-1, thereby cleaving GSDMD-N to cause pyroptosis, and caspase-1^-/- mice were used to verify this conclusion. In addition, we found that EA protects against hepatic IRI by inhibiting pyroptosis, including reducing the activity of caspase-1 and its expression in the liver, inhibiting the lysis of GSDMD-N, and reducing the levels of IL-18 and IL-1β.

Conclusions

The present results have demonstrated that prophylactic administration of EA ameliorated hepatic IRI by inhibiting pyroptosis induced in hepatic ischemia-reperfusion in vivo through the caspase-1-GSDMD axis, providing a potential therapeutic option prevent hepatic IRI in pets.

SUBMITTER: Wang H

PROVIDER: S-EPMC9206301 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Ellagic acid Alleviates hepatic ischemia-reperfusion injury in C57 mice via the Caspase-1-GSDMD pathway.

Wang Hao H Miao Fujun F Ning Delu D Shan Chunlan C

BMC veterinary research 20220618 1

<h4>Background</h4>Ellagic acid (EA) has improving function against oxidative damage and inflammatory reaction in many disorders. Hepatic ischemia-reperfusion injury (IRI) is a common pathophysiological phenomenon in the veterinary clinic. In the present study, the protective effects of EA pretreatment against hepatic IRI-induced injury and the underlying mechanisms were investigated.<h4>Results</h4>We found that pyroptosis is involved in hepatic IRI, which is manifested in increasing the expres ...[more]

PMID: 35717170

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Project description:ObjectivesAlthough a recent study reported that stimulator of interferon genes (STING) in macrophages has an important regulatory effect on liver ischemia-reperfusion injury (IRI), the underlying mechanism of STING-dependent innate immune activation in liver macrophages (Kupffer cells, KCs) remains unclear. Here, we investigated the effect of STING on liver macrophage pyroptosis and the associated regulatory mechanism of liver IRI.MethodsClodronate liposomes were used to block liver macrophages. AAV-STING-RNAi-F4/80-EGFP, an adenoassociated virus (AAV), was transfected into the portal vein of mice in vivo, and the liver IRI model was established 14 days later. In vitro, liver macrophages were treated with STING-specific siRNA, and a hypoxia-reoxygenation (H/R) model was established. The level of STING was detected via Western blotting (WB), RT-PCR, and immunostaining. Liver tissue and blood samples were collected. Pathological changes in liver tissue were detected by hematoxylin and eosin (H&E) staining. Macrophage pyroptosis was detected by WB, confocal laser scanning microscopy (CLSM), transmission electron microscopy (TEM), and enzyme-linked immunosorbent assay (ELISA). The calcium concentration was measured by immunofluorescence and analyzed with a fluorescence microplate reader.ResultsThe expression of STING increased with liver IRI but decreased significantly after the clodronate liposome blockade of liver macrophages. After knockdown of STING, the activation of caspase 1-GSDMD in macrophages and liver IRI was alleviated. More interestingly, hypoxia/reoxygenation (H/R) increased the calcium concentration in liver macrophages, but the calcium concentration was decreased after STING knockdown. Furthermore, after the inhibition of calcium in H/R-induced liver macrophages by BAPTA-AM, pyroptosis was significantly reduced, but the expression of STING was not significantlydecreased.ConclusionsKnockdown of STING reduces calcium-dependent macrophage caspase 1-GSDMD-mediated liver IRI, representing a potential therapeutic approach in the clinic.

Dataset Information

Ellagic acid Alleviates hepatic ischemia-reperfusion injury in C57 mice via the Caspase-1-GSDMD pathway.

Background

Results

Conclusions

Publications

Ellagic acid Alleviates hepatic ischemia-reperfusion injury in C57 mice via the Caspase-1-GSDMD pathway.

Similar Datasets

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