Antioxidants were suggested as possible NF-κB inhibitors many years ago [144, 145]. Treatment with oxidants such as hydrogen peroxide can activate NF-κB in many cell types. In some cell types, antioxidants can inhibit the induction of NF-κB activity in response to a variety of stimuli (e.g., interleukin-1β, LPS, TNFα) [146, 147]. However, using antioxidants as NF-κB inhibitors is now regarded with increasing scepticism because the NF-κB-inhibiting properties of pyrrolidine dithiocarbamate, a thiol-containing compound, cannot be attributed to its antioxidant function but rather to its effects as an inhibitor of IκB ubiquitin ligase activity [148]. The ways in which antioxidants block NF-κB activation remain unclear, but it is likely that they act at different steps in the NF-κB pathway in different cell types. Antioxidants have been suggested to inhibit NF-κB activation by scavenging reactive oxygen intermediates that act as signaling molecules to activate the NF-κB pathway and by directly inhibiting IKK kinase activity by modifying critical Cys residues in the IKK kinase activation loop [146, 147]. Mitochondrial electron transport inhibitors that suppress reactive oxygen intermediate production (e.g., rotenone) and overexpression of
