Endotoxemia is a type of sepsis caused by bacterial lipopolysaccharides (LPS). Sepsis is the body’s overreaction to an infection, which is a life-threatening emergency. Liver disfunction in sepsis is correlated with increased mortality and therefore a cause for great concern. Recently, the search for an effective treatment for sepsis has continued.
Research experiments were performed using a mouse model. The mice were subjected to intraperitoneal injections of LPS, which induced the endotoxemia state. They were also injected with various doses of LGK-974 either prior to, simultaneously, or after the LPS. Several hours after the LPS injection, the mice were anesthetized, and liver and blood samples were collected from each.
The samples were analyzed to assess levels of well-known markers of liver damage and to note any pathological changes in the liver tissue. It was found that the significant changes induced by LPS injection were suppressed in the mice that also received LGK-974 treatment. The timing of the LGK-974 treatment did not make a significant difference. Also, no negative impact was observed in the samples from animals treated with only LGK-974.
In conclusion, this mouse model of sepsis showed positive results of treatment with LGK-974. Bringing the body’s response to the infection under control is the key to overcoming sepsis. This compound is a good candidate for further investigation.
Jang J, Song J, Lee H, et al. LGK974 suppresses lipopolysaccharide-induced endotoxemia in mice by modulating the crosstalk between the Wnt/beta-catenin and NF-kB pathways. Exp Mol Med. 2021 Mar;53(3):407-421. PMID: 33692475