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Chunk #26 — 2. Inhibitors of the NF-κB activation pathway — 2.8. Other mechanisms of NF-κB inhibition — 2.8.2. Antioxidants

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Inhibiting NF-κB activation by small molecules as a therapeutic strategy.
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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 antioxidizing enzymes (e.g., manganese superoxide dismutase and catalase) can block TNFα-induced NF-κB activation [149–151]. Caffeic acid phenethyl ester, a phenolic antioxidant, has been reported to cause direct interference with DNA binding by NF-κB [152] that can be reversed by dithiothreitol [78]. Other antioxidants, viz., N-acetylcysteine, calcium chelators (e.g., EGTA, lacidipine), and vitamin C and E derivatives have been reported to inhibit hydrogen peroxide- or stimulus-induced NF-κB activation.