Direct Interaction between N -Acetylcysteine and Cytotoxic Electrophile—An Overlooked In Vitro Mechanism of Protection.

Keywords: N -acetylcysteine; nucleophile; electrophile; N -acetylcysteine-electrophile adduct; mechanism of protection EN N -acetylcysteine nucleophile electrophile N -acetylcysteine-electrophile adduct mechanism of protection N.PAG N.PAG 18 08/29/22 20220801 NES 220801 1. NAC as a Direct ROS Scavenger In Vitro In laboratory experiments, NAC can counteract many electrophilic agents whose cytotoxicity is accompanied by ROS production and/or by GSH depletion. For this reason, if addition of NAC in experiments is found to prevent GSH depletion, ROS production, and cell death, the logical conclusion is that NAC acts as an indirect ROS scavenger (Figure 2b). Before reaching a definitive conclusion on the mechanism of the cytoprotective effect of NAC, it is appropriate to investigate whether there is a direct interaction between NAC and the cytotoxic electrophile to form a non-cytotoxic NAC-electrophilic adduct. Such an effect of NAC is often used as comprehensive evidence that cell death induced by the cytotoxic agent under study is mediated by increased ROS production and/or GSH depletion and that the protective effect of NAC is mediated by scavenging of ROSs and/or GSH repletion via stimulation of GSH biosynthesis. [Extracted from the article]