Insights into paracetamol poisoning

Glutathione S-transferases (GST) may provide a means for treating fatal liver damage caused by paracetamol overdose. In a paper published in 7 November Proceedings of the National Academy of Sciences, Henderson et al provide a new insight into how the enzyme GST Pi may moderate the toxic effects of paracetamol (acetaminophen).

When overdoses of paracetamol are taken, too much of the compound N-acetyl-p-benzoquinoneimine (NAPQI) is produced; it covalently binds to proteins and other macromolecules to cause cellular damage. NAPQI can be inactivated by binding to glutathione but in paracetamol overdoses there is not enough free glutathione to prevent NAPQI accumulating.

Henderson et al compared paracetamol metabolism in two groups of mice: one normal, the other lacking GST Pi. The mice without any GST Pi were much more resistant to liver damage than normal ones. In both cases when paracetamol was given, free glutathione was quickly depleted. In normal mice this ...