Hydroxyl Radical Generation Mechanism During the Redox Cycling Process of 1,4-Naphthoquinone

Airborne quinones contribute to adverse health effects of ambient particles probably because of their ability to generate hydroxyl radicals (center dot OH) via redox cycling, but the mechanisms remain unclear. We examined the chemical mechanisms through which 1,4-naphthoquinone (1,4-NQ) induced center dot OH, and the redox interactions between 1,4-NQ and ascorbate acid (AscH(2)). First, center dot OH formation by 1,4-NQ was observed in cellular and acellular systems, and was enhanced by AscH2. AscH(2) also exacerbated the cytotoxicity of 1,4-NQ in Ana-1 macrophages, at least partially due to enhanced center dot OH generation. The detailed mechanism was studied in an AscH(2)/H2O2 physiological system. The existence of a cyclic 1,4-NQ process was shown by detecting the corresponding semiquinone radical (NSQ(center dot-)) and hydroquinone (NQH(2)). 1,4-NQ was reduced primarily to NSQ(center dot-) by O-2(center dot-) (which was from AscH(2) reacting with H2O2), not by AscH(2) as normally thought. At lower doses, 1,4-NQ consumed O-2(center dot-) to suppress center dot OH; however, at higher doses, 1,4-NQ presented a positive association with center dot OH. The reaction of NSQ(center dot-) with H2O2 to release center dot OH was another important channel for OH radical formation except for Haber-Weiss reaction. As a reaction precursor for O-2(center dot-), the enhanced center dot 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 center dot OH and a deleterious end point.