Figure 12

The effects of different NAC doses and rescue protocols on liver GSH and functional hepatocytes. Panel A shows time courses liver GSH concentrations and Panel B shows time courses of functional hepatocytes. For all simulations the APAP dose was 22g, which is lethal without NAC rescue. The black curves show the time course of liver GSH and functional hepatocytes with no NAC rescue. The dashed black curves show the effects of rescue with a dose of 36mM NAC given over a one hour period starting two hours after the APAP dose (protocol 1). If we rescue over one hour with twice as much NAC (green dashed curves) or half as much NAC (solid red curves) the results are very similar. However, rescue with 1/10 (solid blue curves) and 1/20 (solid green curves) the normal NAC dose over a one hour period starting at 2 hours show much poorer rescue; at 1/20 the patient’s hepatocytes decline to 30% and survival is in doubt. The dashed red curves and the blue dashed curves show the time courses of liver GSH and functional hepatocytes corresponding to the dosing protocols 2 and 3 as described in the text. In these protocols, the NAC dose is spread out over time. Protocol 3 is better than protocol 2, which is better than protocol 1.