Acute liver failure is characterized by as significant loss of liver function, one of the leading causes of this disease in the US is excessive use of Acetaminophen; a drug commonly used to relieve pain and fever.
In the research presented at the American Society for Investigative Pathology annual meeting during the 2019 Experimental Biology meeting (6—9 April 2019; FL, USA), acetaminophen induced liver failure.
"We are working to identify new drug targets to improve treatment options and reduce the need for liver transplantation, which is often the only option for patients with acute liver failure due to drug toxicity," commented McMillin.
The group found that during liver failure, the protein thrombospondin-1 (TSP-1) interacts with transforming growth factor beta 1 (TGFβ1) – which in turn promotes the degradation of liver cells. Therefore, they rationalized that targeting TSP-1 may provide a viable method for the treatment of liver failure.
"Our study is the first to investigate TSP-1 during acetaminophen toxicity," explained McMillin. "We were able to identify cell communication pathways that do not work properly during acetaminophen-induced liver injury and thus lead to worse outcomes."
In the study, mice treated with acetaminophen were found to have higher levels of TSP-1 than mice with normal liver function. Moreover, when TSP-1 was genetically removed from the acetaminophen treated mice, reduced liver cell damage and death was observed.
In the future, the group plan to manipulate TSP-1 levels in mice models with various therapeutic drugs in order to find out what treatments may work well in clinical studies. Additionally, studies will be conducted on patients with acetaminophen induced liver failure – to determine if these findings from mice are transferable to humans.