naphthoquinones and 9-10-phenanthrenequinone

Air pollutants such as diesel exhaust particles (DEP) are thought to cause pulmonary diseases such as asthma as a result of oxidative stress. While DEP contain a large number of polycyclic aromatic hydrocarbons, we have focused on 9,10-phenanthrenequinone (9,10-PQ) and 1,2-naphthoquinone (1,2-NQ) because of their chemical properties based on their oxidative and chemical modification capabilities. We have found that 9,10-PQ interacts with electron donors such as NADPH (in the presence of enzymes) and dithiols, resulting in generation of excess reactive oxygen species (ROS) through redox cycling. We have also shown that 1,2-NQ is able to modify protein thiols, leading to protein adducts associated with activation of redox signal transduction pathways at lower concentrations and toxicity at higher concentrations. In this review, we briefly introduce our findings from the last two decades.

Topics: Air Pollutants; Antioxidant Response Elements; Asthma; NADP; Naphthoquinones; Oxidation-Reduction; Oxidative Stress; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Reactive Oxygen Species; Signal Transduction; Sulfhydryl Compounds; Vehicle Emissions

Particulate matter with aerodynamic diameter ≤2.5 μm (PM

Topics: Animals; Antigen-Presenting Cells; Benzo(a)pyrene; Bone Marrow Cells; Carbon; Cytokines; Epithelial Cells; Humans; Lymphocytes; Mice; Naphthoquinones; Particulate Matter; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Respiratory Mucosa; Spleen; Vehicle Emissions

A method was developed for the quantification of 1-4 ring quinones in urine samples using liquid-liquid extraction followed by analysis with gas chromatography-mass spectrometry. Detection limits for the ten quinones analyzed are in the range 1-2 nmol dm(-3). The potential use of this approach to monitor urinary quinone levels was then evaluated in urine samples from both Sprague-Dawley rats and human subjects. Rats were exposed to 9,10-phenanthraquinone (PQ) by both injection and ingestion (mixed with solid food and dissolved in drinking water). Urinary levels of PQ were found to increase by up to a factor of ten compared to control samples, and the levels were found to depend on both the dose and duration of exposure. Samples were also collected and analyzed periodically from human subjects over the course of six months. Eight quinones were detected in the samples, with levels varying from below the detection limit up to 3 μmol dm(-3).

Topics: Adult; Animals; Biomarkers; Chrysenes; Environmental Exposure; Female; Gas Chromatography-Mass Spectrometry; Humans; Liquid-Liquid Extraction; Naphthoquinones; Phenanthrenes; Quinones; Rats; Rats, Sprague-Dawley

We have recently purified a tetrameric carbonyl reductase from the cytosolic fraction of pig heart (pig heart carbonyl reductase). Since pig heart carbonyl reductase efficiently reduces all-trans retinal as the endogenous substrate, it probably plays an important role in retinoid metabolism in the heart. The purpose of the present study was to evaluate the inhibitory effects of quinones and flavonoids on the reduction of all-trans retinal to all-trans retinol catalyzed by pig heart carbonyl reductase, using pig heart cytosol. Of quinones tested, 9,10-phenanthrenequinone, a component of diesel exhaust particles, was the most potent inhibitor for the all-trans retinal reduction, and a significant inhibition was also observed for plumbagin and menadione. The order of the inhibitory potencies for flavonoids was kaempferol > quercetin > genistein > myricetin = apigenin = daidzein. However, the inhibitory potencies of flavonoids were much lower than that of 9,10-phenanthrenequinone. 9,10-Phenanthrenequinone competitively inhibited the all-trans retinal reduction, whereas kaempferol exhibited a mixed-type inhibition. It is likely that 9,10-phenanthrenequinone strongly inhibits the reduction of all-trans retinal to all-trans retinol by acting as the substrate inhibitor of pig heart carbonyl reductase present in pig heart cytosol.

Topics: Alcohol Oxidoreductases; Animals; Apigenin; Barbital; Cytosol; Dose-Response Relationship, Drug; Flavonoids; Genistein; Isoflavones; Kaempferols; Kinetics; Molecular Structure; Myocardium; Naphthoquinones; Oxidation-Reduction; Phenanthrenes; Quercetin; Quinones; Retinaldehyde; Swine; Vitamin A; Vitamin K 3

We demonstrate for the first time that agglomerates of multiwalled carbon nanotubes (MWCNTs) can be formed in which the binder in the agglomerate is itself a redox-active molecular solid. Two separate agglomerates were formed by dissolving 9,10-phenanthraquinone (PAQ) or 1,2-napthaquinone (NQ) in acetone together with MWCNTs and adding an excess of aqueous solution to cause precipitation of agglomerates, approximately 10 microns in dimension, which consist of bundles of nanotubes running into and throughout the amorphous molecular solid that binds the agglomerate together. The nature of this structure, when immobilised on a substrate electrode and in contact with aqueous electrolyte solutions, gives rise to many three-phase boundaries, electrolyte|agglomerate|conductor, which is advantageous to the solid-state analytical electrochemistry of such a material as it imparts a larger electroactive surface area than other modified carbon electrodes. The two agglomerates each gave a voltammetrically measurable response to changes in pH; when abrasively immobilised on a basal plane pyrolitic graphite electrode a plot of peak potential against pH produced a linear response for both MWCNT-PAQ and MWCNT-NQ agglomerates over the pH range pH 1-12 and over the temperature range 20-70 degrees C.

Topics: Chemistry, Physical; Electrochemistry; Electrons; Hydrogen-Ion Concentration; Microscopy, Electron, Scanning; Models, Molecular; Nanotubes, Carbon; Naphthoquinones; Oxidation-Reduction; Phenanthrenes; Temperature

Guinea pig lens zeta-crystallin showed hyperbolic saturation curves with 9,10-phenanthrenequinone (PAQ). 5-hydroxy-1,4-naphthoquinone (juglone) and NADPH. Whereas camel lens zeta-crystallin showed hyperbolic saturation curves only with PAQ and NADPH, but slightly segmoidal with juglone. For both enzymes PAQ was the preferred substrate. The catalytic center activity (Kcat) values indicated that camel zeta-crystallin catalyzed the reduction of PAQ more efficiently than the guinea pig lens zeta-crystallin, although the Km values of the two enzymes for this quinone were very similar. The guinea pig lens zeta-crystallin catalyzed the reduction of Juglone far more efficiently than that of the camel lens zeta-crystallin. Juglone did not serve as an efficient substrate for both zeta-crystallins compared to PAQ and appeared to act as a potent competitive inhibitor, with Kl values of 75 nM and 20 microM for guinea pig lens zeta-crystallin and camel lens zeta-crystallin, respectively. Thus, the camel lens zeta-crystallin was less active toward juglone as a substrate as well as less sensitive to its inhibitory action, when compared with guinea pig lens zeta-crystallin. The inhibition mechanism of guinea pig and camel lens zeta-crystallin by juglone is discussed.

Topics: Animals; Camelus; Crystallins; Enzyme Inhibitors; Guinea Pigs; Kinetics; NADP; Naphthoquinones; Phenanthrenes; Quinone Reductases; Structure-Activity Relationship; Substrate Specificity

Studies of the acceptor reductase reaction of yeast glutathione reductase (EC 1.6.4.2) revealed that the competitive inhibitors for NADPH, 2',5'-ADP and Br- decrease the rate constants for the enzyme oxidation by ferricyanide, phenanthrene quinone, and juglone. A similar effect is observed when NADH which does not bind to the reduced enzyme is used as substrate. These observations support the hypothesis that non-physiological redox agents are reduced at the NADP(H)-binding center of glutathione reductase and that NADP(H) binding stimulates the reaction by displacing tyrosine-197 which protects FAD from the solvent.

Topics: Binding Sites; Ferricyanides; Glutathione Reductase; Indicators and Reagents; NADP; Naphthoquinones; Oxidation-Reduction; Phenanthrenes; Saccharomyces cerevisiae