Didox (3,4-Dihydroxybenzohydroxamic acid) is a potent anti-oxidant and anti-inflammatory compound (35.17)

Abstract

Abstract Didox (3,4-Dihydroxybenzohydroxamic acid) is a synthetic antioxidant and one of the most potent ribonucleotide reductase inhibitors developed to date. Little is known about the potential for Didox as an anti-inflammatory agent. After an analysis of more than 200 oxidative stress- and inflammatory-associated genes in mouse RAW264.7 macrophages we show that Didox significantly lowers LPS-induced expression of inflammatory genes (iNOS, IL-1α, IL-1β, IL-6, TNF-α, NF-KB, Cox-2, p38α, TLR4, GM-CSF, G-CSF, CCL2, CCL4, others), while upregulating expression levels of anti-oxidant and anti-inflammatory genes (Catalase, glutathione peroxidase, IL-10, superoxide dismutase, and peroxiredoxins, others). In addition, Didox dose-dependently inhibits LPS-induced IL-6 secretion and nitric oxide production. Buthionine Sulfoximine- and LPS-induced ROS production are also suppressed by Didox. We also show that phagocytosis of yeast particles is decreased as well. In terms of cellular signaling, Didox prevents NF-KB activation and translocation of NF-kappa beta p65 subunits in LPS-treated cells. These results suggest that the mechanism behind anti-oxidant and anti-inflammatory properties of Didox may be mediated, at least in part, via modulation of NF-kappa beta signaling. Didox may, therefore, may hold promise in managing chronic diseases exacerbated by LPS-induced oxidative stress and inflammation in macrophage-mediated inflammation.