title: Hydroxyl radical generation mechanism during the redox cycling process of 1,4-naphthoquinone.
abstract: Airborne quinones contribute to adverse health effects of ambient particles probably because of their ability to generate hydroxyl radicals (·OH) via redox cycling, but the mechanisms remain unclear. We examined the chemical mechanisms through which 1,4-naphthoquinone (1,4-NQ) induced ·OH, and the redox interactions between 1,4-NQ and ascorbate acid (AscH(2)). First, ·OH formation by 1,4-NQ was observed in cellular and acellular systems, and was enhanced by AscH(2). AscH(2) also exacerbated the cytotoxicity of 1,4-NQ in Ana-1 macrophages, at least partially due to enhanced ·OH generation. The detailed mechanism was studied in an AscH(2)/H(2)O(2) physiological system. The existence of a cyclic 1,4-NQ process was shown by detecting the corresponding semiquinone radical (NSQ·-) and hydroquinone (NQH(2)). 1,4-NQ was reduced primarily to NSQ·- by O2·- (which was from AscH(2) reacting with H(2)O(2)), not by AscH(2) as normally thought. At lower doses, 1,4-NQ consumed O2·- to suppress ·OH; however, at higher doses, 1,4-NQ presented a positive association with ·OH. The reaction of NSQ·- with H(2)O(2) to release ·OH was another important channel for OH radical formation except for Haber-Weiss reaction. As a reaction precursor for O2·-, the enhanced ·OH response to 1,4-NQ by AscH(2) was indirect. Reducing substrates were necessary to sustain the redox cycling of 1,4-NQ, leading to more ·OH and a deleterious end point.
authors.affiliation: State Key Laboratory for Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, Peking University, Beijing 100871, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shang
authors.forename: Chenyong
authors.initials: C
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Jincai
authors.initials: J
authors.lastname: Zhao
authors.forename: Tong
authors.initials: T
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D016227:Benzoquinones / Q000737:chemistry; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004578:Electron Spin Resonance Spectroscopy; D017665:Hydroxyl Radical / Q000737:chemistry*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008954:Models, Biological; D009285:Naphthoquinones / Q000737:chemistry* / Q000633:toxicity; D010084:Oxidation-Reduction / Q000187:drug effects
chemical_list: D016227:Benzoquinones; D009285:Naphthoquinones; C025232:semiquinone radicals; D017665:Hydroxyl Radical; D001205:Ascorbic Acid; C035342:1,4-naphthoquinone