New treatment for paracetamol overdose

By targeting the damage that the paracetamol does to the liver, scientists have found a new way to treat paracetamol overdose...

The current coronavirus pandemic means many of us will inevitably be buying - or trying to buy - paracetamol to take advantage of it’s effective control of pain and fever. The usual dose for adults is two 500mg tablets up to 4 times in 24 hours. Anything over 4g/day is defined as an overdose, which happens, unfortunately, all too frequently. In fact, paracetamol overdose is the leading cause of liver damage in Europe and the US. Each year, 80,000 people are hospitalised as a direct result of using the drug. 

At normal doses, paracetamol is safely broken down by cells in the liver. These are normally protected as they degrade a toxic metabolite called NAPQI by antioxidant molecules like the chemical glutathione. This helps to shield the liver cells from damage while this breakdown process occurs. 

But in overdose situations these chemical defences are overwhelmed, leading to the destruction of millions of affected liver cells. And if this damage is too extensive, the ability of the liver to regenerate and replace the injured cells is overwhelmed, leading to potentially fatal liver failure.

The current treatment for paracetamol overdose is a chemical called NAC - N-acetyl cysteine, which helps to restore the liver's glutathione chemical shield. But while this is quite effective, a group from Chapel Hill University in the US have found a new molecule that can combat paracetamol-induced damage directly. This new therapy works by preventing the damage done by NAPQI to liver cells. This is achieved by neutralising the inflammatory action of a protein released from paracetamol-poisoned liver cells.

Mice given the new treatment three hours after receiving what would normally constitute a lethal dose of paracetamol showed significantly lower levels of liver damage than those who were given the existing NAC treatment.

Although more tests need to be done, the team behind the new treatment are hopeful it will help patients who present late to hospital after a potentially lethal overdose. The current treatment’s efficacy greatly depends on patients being treated within just 8 hours. The new agent may buy more time.

“One could imagine this could become part of a dual therapy in the future, as the current treatment is known to work,” says clinical scientist Christof Gaunt, commenting on the new findings. “Because, at these early time points, it seems very effective.”