Prevent damage caused by drug-liver
Researchers from Massachusetts General Hospital have developed a new strategy to protect the liver from damage induced by drugs and improve drug safety. In their report, published in the journal Nature Biotechnology, the team reports that the inhibition of cellular communication type can protect against damage caused by toxic drugs to the liver, such as acetaminophen. “Our findings suggest that this therapy could be a clinically viable strategy for treating patients with drug-induced liver damage,” says Dr. Suraj Patel, Department of Surgery, Massachusetts General Hospital, author of the paper, adding that “This work also has the potential to change the way drugs are developed and formulated, which could improve drug safety by getting a lower risk of liver toxicity.”
Develop, approve and prescribe a drug requires that the therapeutic benefits outweigh the potential side effects. Liver toxicity limits the development of many therapeutic compounds, and presents major challenges for clinical medicine and the pharmaceutical industry. The drug-induced liver injury is the most common cause of acute liver failure in the U.S., and is also the most common reason for early withdrawal of certain treatments. Since there are currently no pharmaceutical strategies for the prevention of drug-induced liver injury, treatment options are limited to discontinuing the offending drug, supportive care and liver transplantation for end-stage failure.
Gap junctions (gap junctions) are hollow channels that connect neighboring cells and allow direct intercellular communication between coupled cells. In the heart, these unions propagate electrical activity necessary for contraction, but so far, its role in the liver was poorly defined. Now, this new study has shown that the sets of signals broadcast junctions immune injured liver cells to nearby cells in good condition, extending the general inflammation and injury.
First, the researchers used a genetically mutated strain of mice lacking gap junctions, the rats were given several medications toxic to the liver, such as paracetamol (acetaminophen), commonly used acetaminophen overdose is the most frequent drug-induced liver damage. Compared to normal mice, these mice were shown to be protected against liver damage, inflammation and death caused by the administration of toxic drugs to the liver.
The team identified an inhibitor of liver gap junctions, when administered with, or even after, toxic drugs, protected the livers of normal mice from harm. In addition, cell culture experiments indicate that blocking these junctions limits the diffusion through the liver cells from free radicals and oxidative stress.
A patent related to this study has been presented by Partners Healthcare, and Heprotech Inc. According to the researchers, “the findings of this study suggest a strategy of developing new drugs safe for the liver.”