Abstract
Dihydromyricetin (DHM), a flavonoid in vine tea, has many pharmacological activities, including anti-inflammatory and antibacterial effects. Lipopolysaccharide is the key inducer of inflammation in avian pathogenic Escherichia coli (E. coli) infection; however, the effect of DHM on E. coli lipopolysaccharide-induced hepatic injury remains unknown. The present study aimed to explore the role of the NLRP3 inflammasome in hepatic injury and the possible protective mechanisms of DHM against hepatic injury in chickens. The results showed that when chickens were administered lipopolysaccharide, liver damage was observed, accompanied by increased levels of serum transaminases and direct bilirubin. Additionally, hepatic expression levels of NLRP3 and caspase-1 p20, the subunit of caspase-1 that is cleaved after NLRP3 activation, significantly increased in liver injury. We found that treatment with MCC950, a specific NLRP3 inhibitor, significantly decreased serum transaminase activities, direct bilirubin content, and hepatic NLRP3 and caspase-1 p20 expression levels. DHM significantly reduced serum transaminase activities and direct bilirubin content and ameliorated histopathological and ultrastructural changes in the liver. DHM decreased hepatic levels of H2O2 and malondialdehyde and increased the activities of superoxide dismutase and glutathione peroxidase. Furthermore, DHM significantly decreased the expression levels of NLRP3, pro-caspase-1 and caspase-1 p20. Moreover, DHM reduced serum lactate dehydrogenase, IL-1β and IL-18 levels and repressed hepatic IL-1β, IL-18 and gasdermin A expression. The results demonstrated that the NLRP3 inflammasome was involved in the mechanism of lipopolysaccharide-induced hepatic injury. Furthermore, DHM could inhibit NLRP3 inflammasome activation and subsequent pyroptosis, eventually ameliorating E. coli lipopolysaccharide-induced liver injury.
Highlights
Avian pathogenic Escherichia coli (APEC), a gram-negative bacterium, is an important pathogen that causes infectious bacterial diseases, seriously threatening theShi et al Veterinary Research (2022) 53:6 after bacterial death and enter the liver via the portal vein along with other substances from the intestines
Ultrastructural analysis showed that liver tissues from LPS-treated chickens had chromatin aggregation around the nuclear membrane, increased space between the inner and outer nuclear membrane, decreased glycogen and swollen mitochondria compared with liver tissues from saline-treated chickens (Figure 1C)
These results show that LPS could cause severe hepatic injury
Summary
Avian pathogenic Escherichia coli (APEC), a gram-negative bacterium, is an important pathogen that causes infectious bacterial diseases, seriously threatening theShi et al Veterinary Research (2022) 53:6 after bacterial death and enter the liver via the portal vein along with other substances from the intestines. Hepatic injury is considered a risk factor for gram-negative bacterial infection because of the inability of the liver to clear bacteria or LPS [5]. It is necessary to find novel agents that prevent and treat LPS-induced hepatic injury. Active caspase-1 promotes the cleavage of pro-IL-1β and pro-IL-18 into mature IL-1β and IL-18 [7, 8]. Active caspase-1 promotes the cleavage of gasdermin protein followed by the formation of pores in the cell membrane [9]. Pyroptosis is a novel form of programmed cell death and is executed by gasdermins, a family of pore-forming effector proteins. The NLRP3 inflammasome and pyroptosis have been studied in mammals, but it is unclear whether they are involved in LPS-induced hepatic injury in chickens
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