Abstract
Florfenicol (FFC), a widely used drug for chicken diseases, can aggravate lipopolysaccharide (LPS) damage to the liver. For this condition, natural or synthetic products displaying strong antioxidant capacity are expected to prevent LPS/FFC from inducing liver injury, so in our study, the compound ammonium glycyrrhizin (CAG) is used as the protective drug to decrease the injury to liver. The research aims to illustrate the underlying mechanism of combining LPS with FFC-induced liver injury and the protective role of CAG by using primary chicken hepatocytes as an in vitro model. The results show that LPS/FFC induced cell apoptosis and CAG protected hepatocytes from injury. The permeability of the cell membrane is elevated by LPS/FFC, leading to the efflux of enzymes (ALT, AST). Flow cytometry analysis indicates that LPS/FFC treatment increased the apoptosis rate significantly. Furthermore, with the up-regulation of apoptosis genes bax, cytochrome c and the down-regulation of bcl-2, caspase-3 and caspase-9 are activated at the gene level. LPS/FFC-induced mitochondrial damage is accompanied by a significant decrease in mitochondrial membrane potential (MMP) and severe mitochondrial damage. However, CAG improves the situation for the purpose of protecting the liver. In conclusion, it is speculated that LPS/FFC induces severe liver injury through apoptosis and the CAG protects hepatocytes from injury via the mitochondria-mediated apoptosis pathway.
Highlights
It is speculated that LPS/FFC induces severe liver injury through apoptosis and the compound ammonium glycyrrhizin (CAG) protects hepatocytes from injury via the mitochondria-mediated apoptosis pathway
Drug-induced liver injury, the most common cause of acute liver failure in the United States [1], is a common clinical manifestation which may be a challenge to all liver related diseases [2]
Primary chicken hepatocytes were used as the in vitro model to investigate whether FFC can aggravate the liver injury caused by LPS and the protective mechanism of CAG
Summary
Drug-induced liver injury, the most common cause of acute liver failure in the United States [1], is a common clinical manifestation which may be a challenge to all liver related diseases [2]. Severe drug-induced liver injury causes a series of diseases which can eventually lead to hospitalization [1,3]. It is reported that antibiotics are a common cause of liver failure next to drug-induced liver injury (DILI) [4,5,6]. Florfenicol (FFC) is a broad-spectrum antibiotic for animals [7], which has great antibacterial effects on many Gram negative bacteria and positive bacteria. If nano-LPS is mistakenly injected into the blood, it will cause septic shock in humans and symptoms of liver injury in animals [10]
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