University of Adelaide researchers have identified a key
step for the future prevention of liver failure resulting from taking too much
of the everyday painkiller paracetamol (also known as acetaminophen).
Published today in the Proceedings of the National Academy
of Sciences (PNAS), the study pinpoints a target for new treatments to prevent
the potentially lethal consequences of paracetamol overdose.
may damage liver
"Paracetamol is the most frequently used
over-the-counter pain medication," says Dr Grigori Rychkov, Senior
Research Fellow in the University's School of Medical Sciences.
Acute liver failure
"Overdose of paracetamol is the most common cause of
acute liver failure and the leading cause of liver damage requiring
transplantation in developed countries. The precise mechanisms of liver
toxicity due to paracetamol overdose, however, have remained unclear."
It has been known for a long time that paracetamol overdose
is associated with toxic levels of calcium in liver cells but nobody has known
how the calcium gets into the cells.
The University of Adelaide researchers have identified a
channel transporting calcium across the cell membrane that is triggered by
paracetamol overdose, known as Transient Receptor Potential Melanostatine2
(TRPM2). Once the channel is activated, the cells become overloaded with
calcium, leading to cell death. If this continues and enough cells die, it can
lead to liver failure.
overdoses on the rise
The research, conducted by PhD student Ehsan Kheradpezhouh,
showed in laboratory studies that when the TRPM2 channel was missing or
blocked, liver cells were protected from paracetamol damage.
A better chance for recovery
"We now have a potential drug target for treating
paracetamol overdose and possibly some other liver-damaging poisonings,"
says Dr Rychkov.
Currently paracetamol overdose can be effectively treated –
but only if caught within 18 hours.
"If we can block the TRPM2 channel we might be able to
prevent the toxicity or extend this timeframe. If we can stop the calcium
uptake and cell death, we'll be giving the liver a better chance for recovery
and, hopefully, preventing complete liver failure," says Dr Rychkov.
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