Stephen A. Munk hypothesizes that acetaminophen owes its toxic effects (including a recently discovered link to asthma) to a mechanism involving metabolic oxidation of its hydroquinone-like structure followed by reaction with essential nucleophiles and glutathione depletion (C&EN, March 26, page 7). He suggests that “this line of work is worth pursuing,” but this mechanism is already well-known.
As shown, acetaminophen, a widely used analgesic drug, is rapidly metabolized to a hepatotoxic N-acetyl-p-quinone intermediate by a number of cytochrome P450 enzymes. Acetaminophen’s analgesic and antipyretic properties are due to the inhibition of cyclooxygenase enzymes involved in prostaglandin synthesis. Limited amounts of acetaminophen may be safely ingested, but larger amounts fully deplete the stores of glutathione and can lead to liver failure or even death.
Warnings about this are printed on every package of acetaminophen.
By Manfred E. Wolff
Laguna Beach, Calif