Biological effects of menadione photochemistry: effects of menadione on biological systems may not involve classical oxidant production

McCormick, Michael L.; Denning, Gerene M.; Reszka, Krzysztof J.; Bilski, Piotr; Buettner, Garry R.; Rasmussen, George T.; Railsback, Michelle A.; Britigan, Bradley E.

doi:10.1042/bj3500797

Cited by 10 publications

(3 citation statements)

References 22 publications

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“…Thus, the DMPO/ • OH signal is not an indication of the formation of superoxide or hydroxyl radicals in the reaction system. It may be a background signal or it may arise from the oxidation of DMPO by photoexcited 2,6-DCBQ. , The mechanism we propose is analogous to that proposed previously by Monroe and Eaton (1996) for menadione: …”

Section: Resultssupporting

confidence: 79%

Characterization of Mechanisms of Glutathione Conjugation with Halobenzoquinones in Solution and HepG2 Cells

Wang

Qian

et al. 2018

Environ. Sci. Technol.

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Halobenzoquinones (HBQs) are a class of emerging disinfection byproducts. Chronic exposure to chlorinated drinking water is potentially associated with an increased risk of human bladder cancer. HBQ-induced cytotoxicity involves depletion of cellular glutathione (GSH), but the underlying mechanism remains unclear. Here we used ultrahigh performance liquid chromatography-high resolution mass spectrometry and electron paramagnetic resonance spectroscopy to study interactions between HBQs and GSH and found that HBQs can directly react with GSH, forming various glutathionyl conjugates (HBQ-SG) in both aqueous solution and HepG2 cells. We found that the formation of HBQ-SG varies with the initial molar ratio of GSH to HBQ in reaction mixtures. Higher molar ratios of GSH to HBQ facilitate the conjugation of more GSH molecules to an HBQ molecule. We deduced the reaction mechanism between GSH and HBQs, which involves redox cycling-induced formation of halosemiquinone (HSQ) free radicals and glutathione disulfide, Michael addition, as well as nucleophilic substitution. The proposed reaction rates are in the following order: formation of HSQ radicals > substitution of bromine by GSH > Michael addition of GSH on the benzoquinone ring > substitution of chlorine by GSH > substitution of the methyl group by GSH. The conjugates identified in HBQ-treated HepG2 cells were the same as those found in aqueous solution containing a 5:1 ratio of GSH:HBQs.

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Section: Resultssupporting

confidence: 79%

Characterization of Mechanisms of Glutathione Conjugation with Halobenzoquinones in Solution and HepG2 Cells

Wang

Qian

et al. 2018

Environ. Sci. Technol.

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“…The possibility also exists that the complex I NADH-ubiquinone reductase is a nitroreductase itself, perhaps aided by semiquinone as a reductant, to render the ROT inhibition effective. MD also generates a superoxide anion and hydrogen peroxide; 91,92 however, its effect on 1-AP production did not reach statistical significance in A549 cells. The lack of a significant effect of MD implies that its target(s) (i.e., AOX) do not act as an aerobic 1-NP nitroreductase.…”

Section: ■ Discussionmentioning

confidence: 82%

Role of Human Aldo-Keto Reductases and Nuclear Factor Erythroid 2-Related Factor 2 in the Metabolic Activation of 1-Nitropyrene via Nitroreduction in Human Lung Cells

Penning

2023

Chem. Res. Toxicol.

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1-Nitropyrene (1-NP) is a constituent of diesel exhaust and classified as a group 2A probable human carcinogen. The metabolic activation of 1-NP by nitroreduction generates electrophiles that can covalently bind DNA to form mutations to contribute to cancer causation. NADPH-dependent P450 oxidoreductase (POR), xanthine oxidase (XO), aldehyde oxidase (AOX), and NAD(P)H/quinone oxidoreductase 1 (NQO1) may catalyze 1-NP nitroreduction. We recently found that human recombinant aldo-keto reductases (AKRs) 1C1–1C3 catalyze 1-NP nitroreduction. NQO1 and AKR1C1–1C3 are genes induced by nuclear factor erythroid 2-related factor 2 (NRF2). Despite this knowledge, the relative importance of these enzymes and NRF2 to 1-NP nitroreduction is unknown. We used a combination of pharmacological and genetic approaches to assess the relative importance of these enzymes and NRF2 in the aerobic nitroreduction of 1-NP in human bronchial epithelial cells, A549 and HBEC3-KT. 1-NP nitroreduction was assessed by the measurement of 1-aminopyrene (1-AP), the six-electron reduced metabolite of 1-NP, based on its intrinsic fluorescence properties (λex and λem). We found that co-treatment of 1-NP with salicylic acid, an AKR1C1 inhibitor, or ursodeoxycholate, an AKR1C2 inhibitor, for 48 h decreased 1-AP production relative to 1-NP treatment alone (control) in both cell lines. R-Sulforaphane or 1-(2-cyano-3,12,28-trioxooleana-1,9(11)-dien-28-yl)-1H-imidazole (CDDO-Im), two NRF2 activators, each increased 1-AP production relative to control only in HBEC3-KT cells, which have inducible NRF2. Inhibitors of POR, NQO1, and XO failed to modify 1-AP production relative to control in both cell lines. Importantly, A549 wild-type cells with constitutively active NRF2 produced more 1-AP than A549 cells with heterozygous expression of NFE2L2/NRF2, which were able to produce more 1-AP than A549 cells with homozygous knockout of NFE2L2/NRF2. Together, these data show dependence of 1-NP metabolic activation on AKR1Cs and NRF2 in human lung cells. This is the second example whereby NFE2L2/NRF2 is implicated in the carcinogenicity of diesel exhaust constituents.

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“…Under proper photoirradiation, groundstate MSB can be excited to the singlet state followed by ISC and the formation of a triplet state (Figure 1a), the latter of which is widely thought of as the starting material in various photoreactions due to its relatively long lifetime and oxidative property. 22,25 Several subsequent reactions could occur to MSB after the formation of the triplet state, such as electron transfer 26 or a hydrogen abstraction reaction from substrates, 27 singlet oxygen sensitization, 28 and microbial oxidation and disruption. 15 A UV−vis absorption spectrum of MSB was The prominent absorption peaks of MSB in the UVB region can be attributed to its multiple singlet excited states, such as S 5 (279.86 nm) and S 13 (235.76 nm), based on computational modeling.…”

Section: ■ Introductionmentioning

confidence: 99%

Photoactive Water-Soluble Vitamin K: A Novel Amphiphilic Photoinduced Antibacterial Agent

Zhang

Wisuthiphaet

Nitin

et al. 2021

ACS Sustainable Chem. Eng.

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Menadione sodium bisulfite (MSB), also known as water-soluble vitamin K3 widely used as an animal food additive due to its low toxicity and low cost, is for the first time proven to be photoactive and antibacterial under various photoirradiation sources, evidenced by a computational modeling method and well-designed experiments. MSB demonstrates its robust photoactivity and application potential under ultraviolet A (UVA, 315–400 nm) irradiation. The results reveal that MSB could effectively generate reactive oxygen species (ROS) under UVA irradiation due to the formation of its oxidative triplet excited state. The photoinduced antibacterial tests also demonstrate the nonselective bacterial inactivation functions of MSB under proper photoirradiation. MSB was challenged against Gram-negative Escherichia coli (E. coli) and Gram-positive Listeria innocua (L. innocua) under UVA irradiation and exhibited excellent antibacterial performance (99.999% bacterial inactivation in 30 min of UVA exposure) in PBS. The antibacterial performance of MSB does not decay after five times of repeated exposures to bacteria and UVA irradiation, indicating the photostability and durability of MSB as a photoinduced antibacterial agent. More interestingly, solvents played a significant role in photoinduced antibacterial properties but not in the generation of ROS of MSB, indicating that the solvents may serve as contact media between MSB and bacteria cells. Intimate contact of MSB and microorganisms is thought of as a determinant in the bacterial inactivation by ROS or triplet excited states due to their relatively short lifetime and limited diffusion and function radius.

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Biological effects of menadione photochemistry: effects of menadione on biological systems may not involve classical oxidant production

Cited by 10 publications

References 22 publications

Characterization of Mechanisms of Glutathione Conjugation with Halobenzoquinones in Solution and HepG2 Cells

Characterization of Mechanisms of Glutathione Conjugation with Halobenzoquinones in Solution and HepG2 Cells

Role of Human Aldo-Keto Reductases and Nuclear Factor Erythroid 2-Related Factor 2 in the Metabolic Activation of 1-Nitropyrene via Nitroreduction in Human Lung Cells

Photoactive Water-Soluble Vitamin K: A Novel Amphiphilic Photoinduced Antibacterial Agent

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