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.

Hemolysin Co-Regulatory Protein 1 Enhances the Virulence of Clinically Isolated Escherichia coli in KM Mice by Increasing Inflammation and Inducing Pyroptosis

“…The procedure for Western blot analysis has been reported [ 19 ]. Briefly, kidney tissues were collected according to the experimental protocol.…”

“…The classical pathway of pyroptosis is mediated by caspase-1 [ 16 ]. In the classical pathway of pyroptosis, NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome assembly initiates the proteolytic cleavage of dormant pro-caspase-1 into active caspase-1, which transforms the cytokine precursors pro-IL-1β and pro-IL-18 into mature and biologically active interleukin-1β (IL-1β) and interleukin-18 (IL-18) [ 14 , 17 , 18 , 19 ]. In addition, lipopolysaccharide (LPS) is a typical bacterial toxin protein that can activate caspase-11 to induce pyroptosis [ 20 ].…”