The hepatoprotective effect of N-acetylcysteine in acetaminophen intoxication is due to early glutathione replenishment via stimulation of anaplerotic mechanisms.
Raymond V, Chan T, Zwingmann C, Bilodeau M, Leibfritz D
Acetaminophen (AAP) is converted by the cytochrome P450 pathway to a toxic intermediate, N-acetyl-p-benzoquinone-imine (NAPQI), which is usually completely detoxified through combination with glutathione (GSH). N-acetylcysteine (NAC) is believed to act by regenerating glutathione (GSH) stores. We wanted to identify the effect of NAC on metabolic pathways in mouse liver. After AAP treatment, a rapid depletion of GSH stores parallels a considerable inhibition of anaplerotic flux. Krebs cycle metabolism of acetate, however, was unchanged after AAP treatment, but stimulated by NAC. These data suggest that anaplerotic fluxes play a key role for GSH resplenishment after AAP intoxication.