N-Acetylcysteine: Antioxidant, Aldehyde Scavenger, and More

N-Acetylcysteine is a commonly used antioxidant that is broadly effective despite its limited reactive oxygen species (ROS) reactivity. Chemoprotection by N-acetylcysteine frequently results from inactivation of primary toxicants or reactive electrophiles arising as metabolites or lipid peroxidation products. ROS are linked to the development of many human diseases and biological injury by numerous xenobiotics. Oxidative damage is the first mechanism that is often tested for toxicants. There is also a frequent projection of the established ROS mechanism for one member to a broader group to which this chemical belongs. However, the biological significance of oxidative processes is not always easy to establish, as oxidants could be a cause or result of cellular injury. The role of ROS is tested through genetic manipulations of oxidative stress-protective proteins and addition of small antioxidants. In general, genetic approaches produce protective effects weaker than those of small antioxidants, which can reflect different anti-ROS specificity. Another possibility is that chemical antioxidants have ROS-unrelated chemoprotective activities.