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

BMC Vet Res. 2022 Jun 18;18(1):229. doi: 10.1186/s12917-022-03326-0.

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.

Keywords: Caspase-1-GSDMD pathway; Ellagic acid; Hepatic IRI; Pyroptosis.

MeSH terms

  • Animals
  • Caspase 1 / metabolism
  • Ellagic Acid / metabolism
  • Ellagic Acid / pharmacology
  • Ellagic Acid / therapeutic use
  • Liver / metabolism
  • Mice
  • Pyroptosis
  • Reperfusion Injury* / drug therapy
  • Reperfusion Injury* / prevention & control
  • Reperfusion Injury* / veterinary

Substances

  • Ellagic Acid
  • Caspase 1