The common painkiller, paracetamol (known more commonly as acetaminophine in the United States), causes liver damage, but now scientists have found insights into how the damage occurs – and that may lead to new therapies to counteract the sometimes fatal damage.
This is important because paracetamol is the leading cause of acute liver failure in the Western world.
Scientists at the University of Edinburgh studied the impact of paracetamol on liver cells in human and mouse tissue. Tests showed that paracetamol can damage the liver by harming vital structural connections between adjacent cells in the organ.
When these cell wall connections – known as tight junctions – are disrupted, they cause damage to the liver tissue structure, then the cells are unable to function properly and they can die.
This type of cell damage is known to occur in liver conditions including hepatitis, cirrhosis, and cancer, but until now it was not linked to paracetamol toxicity.
“Paracetamol is the world’s preferred pain remedy – it is cheap, and considered safe and effective at therapeutic dose. However, drug-induced liver damage remains an important clinical problem and a challenge for developing safer drugs. Our findings reinforce the need for vigilance in paracetamol use, and could help discover how harm caused by its adverse use might be prevented,” said Dr Leonard Nelson, of the University of Edinburgh’s Hepatology Laboratory and Institute for Bioengineering, who co-led the study.
Researchers are now looking to develop a reliable method of using human liver cells as an alternative to animal testing, and look to understand the impact of paracetamol doses on liver toxicity.
“Although liver damage caused by paracetamol toxicity has been the subject of intense study for 40 years, recent developments in biosensor technology are enabling a fuller picture of the biological mechanisms involved,” said co-author Pierre Bagnaninchi, of the University’s MRC Centre for Regenerative Medicine.
The study, involving researchers from the Universities of Edinburgh and Oslo and the Scottish National Blood Transfusion Service, was published in Scientific Reports.