DIDOX MODULATES REACTIVE OXYGEN SPECIES PRODUCTION AND INFLAMMATORY EVENTS INDUCED BY LIPOPOLYSACCHARIDE (LPS) AND ARYL HYDROCARBON RECEPTOR (AHR) LIGANDS IN RAW 264.7 MURINE MACROPHAGES.

Aberrant activation of macrophages during inflammation results in oxidative burst release of reactive oxygen and reactive nitrogen species (ROS/RNS) which are widely accepted to participate in pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer\u27s disease and Parkinson\u27s disease), rheumatoid arthritis, and ageing. It is demonstrated here that Didox (3,4-Dihydroxybenzohydroxamic acid) possesses antioxidative and anti-inflammatory properties that can protect against inflammation and oxidative stress induced by lipopolysaccharide (LPS) and aryl hydrocarbon receptor (AHR) ligands (PCB126, E804, and IO) in Raw 264.7 murine macrophages. In brief, it is demonstrated here that Didox inhibits LPS-induced oxidative stress, ROS/RNS generations, IL-6 production, NO production, phagocytic activity, and NF-kappa B nuclear translocation in Raw 264.7 murine macrophages. Furthermore, Didox downregulated ROS production, cytochrome P450 1A1 (CYP1A1), and AHR nuclear translocation induced by PCB126, E804, and IO in Raw 264.7 murine macrophages. These data suggest that oxidative stress regulatory effects of Didox may be useful in managing inflammatory diseases conditions initiated by exposure to AHR activating xenobiotics or LPS