title: Enzymatic redox reactions of the explosive 4,6-dinitrobenzofuroxan (DNBF): implications for its toxic action.
abstract: With an aim to understand the toxicity mechanisms of the explosive 4,6-dinitro- benzofuroxan (DNBF), we studied its single-electron reduction by NADPH:cytochrome P450 reductase and ferredoxin:NADP(+) reductase, and two- electron reduction by DT-diaphorase and Enterobacter cloacae nitroreductase. The enzymatic reactivities of DNBF and another explosive 2,4,6-trinitrotoluene (TNT) were similar, except for the much lower reactivity of DNBF towards nitroreductase. DNBF was less cytotoxic in FLK cells than TNT. However, their action shared the same mechanisms, oxidative stress and activation by DT-diaphorase. The lower cytotoxicity of DNBF may be explained by the negative electrostatic charge of its adduct with water which may impede cellular membrane penetration, and by the formation of its less reactive adducts with intracellular reduced glutathione.
authors.affiliation: Institute of Immunology, Moletu Pl. 29, Vilnius 2021, Lithuania.
authors.forename: Ausra
authors.initials: A
authors.lastname: Nemeikaite-Ceniene
authors.forename: Jonas
authors.initials: J
authors.lastname: Sarlauskas
authors.forename: Lina
authors.initials: L
authors.lastname: Miseviciene
authors.forename: Zilvinas
authors.initials: Z
authors.lastname: Anusevicius
authors.forename: Audrone
authors.initials: A
authors.lastname: Maroziene
authors.forename: Narimantas
authors.initials: N
authors.lastname: Cenas
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival; D004136:Dinitrobenzenes / Q000737:chemistry / Q000633:toxicity*; D005287:Ferredoxin-NADP Reductase / Q000378:metabolism*; D007700:Kinetics; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D010084:Oxidation-Reduction; D014303:Trinitrotoluene / Q000737:chemistry / Q000633:toxicity
chemical_list: C454325:4,6-dinitrobenzofuroxan; D004136:Dinitrobenzenes; D014303:Trinitrotoluene; D005287:Ferredoxin-NADP Reductase; D009251:NADPH-Ferrihemoprotein Reductase