How does N-acetylcysteine work for acetaminophen toxicity?

Acetaminophen (paracetamol) is a widely available medication used to treat fever and pain. It is also the leading cause of liver transplantation in the U.S. and the second leading cause worldwide due to liver toxicity that can occur with overdose. When acetaminophen is overdosed, a toxic metabolite (N-acetyl-p-benzoquinone imine (NAPQI)) begins to build up in the liver. Normally, glutathione is responsible for neutralizing NAPQI, but when glutathione levels become depleted, NAPQI begins reacting with molecules within liver cells, leading to irreversible liver cell death. NAC is an effective antidote for acetaminophen (paracetamol) toxicity primarily because it replenishes glutathione levels, but it can also directly bind to and neutralize NAPQI to minimize liver cell damage and convert NAPQI back to acetaminophen temporarily.^[1]