Scientists discover a new therapeutic target for liver failure from drug-induced

Acetaminophen – a commonly used badgesic and fever reducer – is the leading cause of acute or rapidly developing liver failure in the United States. Results from a new study in mice suggest that treatments that increase thrombospondin-1 protein levels could help the liver recover from an overdose of acetaminophen.

"The only treatment currently available for acetaminophen overdose is to be administered early, before severe liver injury occurs," said Matthew McMillin, Ph.D., who led the research. "We are working to identify new target drugs to improve treatment options and reduce the need for liver transplantation, which is often the only option available for patients with liver failure." acute because of drug toxicity. "

McMillin, an badistant professor at the University of Texas at Austin and a research biologist at the Central Texas Veterans Health Care System, will present the research at the annual meeting of the American Society for Investigative Pathology at the 2019 meeting on experimental biology to be held in Orlando, Florida

McMillin and colleagues found that mice with acute liver failure due to acetaminophen toxicity had higher thrombospondin-1 levels than mice with normal hepatic function. When they administered acetaminophen to genetically modified mice lacking thrombospondin-1, hepatic injury and loss of liver function were more severe than in unmodified mice. The researchers also observed an alteration of liver regeneration and an increase in cell death in mice without thrombospondin-1.

"Our study is the first to study thrombospondin-1 during the toxicity of acetaminophen," McMillin said. "We have been able to identify cellular communication pathways that are not functioning properly during acetaminophen-induced liver injury, resulting in degradation of results."

The researchers then plan to administer various thrombospondin-1 medications to the mouse to determine the treatment that may be appropriate for potential clinical trials. They also plan to examine patients with acute acetaminophen-induced hepatic impairment to determine whether their thrombospondin-1 results in mice are true in humans.

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Experimental Biology