Abstract

Nuclear factor (NF)-kappa B is a redox sensitive cytosolic transcription factor. Redox regulation of NF-kappa B has been implicated in the activation of the human immuno-deficiency virus (HIV). Therefore, inhibition of NF-kappa B activation may be an effective strategy for acquired immunodeficiency syndrome therapy. Anetholdithiolthione (ADT, 5-[p-methoxyphenyl]-3H-1,2-dithiol-3-thione) is an antioxidant which has been used to protect against acetaminophen- and CCl4-induced hepatotoxicity, lipid peroxidation, radiation injury, and also has been used clinically as an anti-choleretic agent. The present study examined the effect of ADT pretreatment on NF-kappa B activation in response to a variety of stimuli such as H2O2, phorbol myristate acetate (PMA) or tumor necrosis factor alpha (TNF alpha). PMA and TNF alpha induced activation of (NF)-kappa B in human Jurkat T-cells was partially inhibited by ADT (0.1 mM) pretreatment. ADT (0.1 mM) also inhibited H2O2 induced activation of the transcription factor in the peroxide sensitive human Wurzburg T-cells. Furthermore, ADT treated Wurzburg cells had significantly higher glutathione levels as compared with untreated cells. H2O2 induced lipid peroxidation in Wurzburg cells was remarkably inhibited by ADT pretreatment. ADT, a pro-glutathione antioxidant, was observed to be capable of modulating NF-kappa B activation.