1.Impact of dioxins on antipyrine metabolism in firefighters.
Chernyak YI1, Merinova AP2, Shelepchikov AA3, Kolesnikov SI2, Grassman JA4. Toxicol Lett. 2016 Apr 8. pii: S0378-4274(16)30058-3. doi: 10.1016/j.toxlet.2016.04.006. [Epub ahead of print]
Antipyrine (AP) metabolism was used to assess factors associated with the activity of hepatic oxidative enzymes in firefighters. Emphasis was placed on 3-hydroxymethylantipyrine (3HMAP), the metabolite with the greatest dependence on dioxin-inducible cytochrome P4501A2 (CYP1A2) activity. AP urinary metabolites were measured by HPLC in 38 male subjects from Eastern Siberia. Subjects were divided into three groups having similar ages and BMIs: current firefighters (n=11); former firefighters (n=17) and non-firefighters (n=10). Multiple regression models were constructed using the three major AP metabolites as dependent variable to assess the influence of age, smoking as urinary cotinine concentration, dioxin exposure (as either WHO-TEQ or body burden), group, and CYP1A2*F (-163C>A) genotypes. Models for the proportion of dose excreted as the metabolite 3HMAP produced the best fit (adjusted R2=0.46, p<0.05). When the models were restricted to current firefighters, only those based on 3HMAP were statistically significant (adjusted R2 of 0.
2.Pyrazolones metabolites are relevant for identifying selective anaphylaxis to metamizole.
Ariza A1, García-Martín E2, Salas M3, Montañez MI1,4, Mayorga C1, Blanca-Lopez N5, Andreu I6, Perkins J1, Blanca M3, Agúndez JA2, Torres MJ3. Sci Rep. 2016 Mar 31;6:23845. doi: 10.1038/srep23845.
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common cause of hypersensitivity reactions, with pyrazolones the most frequent drugs inducing selective reactions. Immediate selective hypersensitivity to pyrazolones is thought to be mediated by specific-IgE. Sensitivity of in vitro diagnostic tests is low and this may be due to the incomplete characterization of the structures involved. Here we investigated whether main metabolites of metamizole (dipyrone) in human could be involved in the immune response using the basophil activation test (BAT). We studied subjects with confirmed selective immediate hypersensitivity to metamizole and performed BAT with metamizole and its metabolites: 4-methylamino-antipyrine (MAA), 4-aminoantipyrine (AA), 4-acetylamino-antipyrine (AAA) and 4-formylamino-antipyrine (FAA). BAT results showed an increase of positive results from 37.5% to 62.5% using metamizole plus metabolites as compared with the BAT carried out only with the parent drug, demonstrating that metamizole metabolites have a role in the reaction and can induce specific basophil activation in patients with immediate hypersensitivity to this drug.
3.Zr-doped TiO2 supported on delaminated clay materials for solar photocatalytic treatment of emerging pollutants.
Belver C1, Bedia J2, Rodriguez JJ2. J Hazard Mater. 2016 Feb 15. pii: S0304-3894(16)30148-0. doi: 10.1016/j.jhazmat.2016.02.028. [Epub ahead of print]
Solar light-active Zr-doped TiO2 nanoparticles were successfully immobilized on delaminated clay materials by a one-step sol-gel route. Fixing the amount of TiO2 at 65wt.%, this work studies the influence of Zr loading (up to 2%) on the photocatalytic activity of the resulting Zr-doped TiO2/clay materials. The structural characterization demonstrates that all samples were formed by a delaminated clay with nanostructured anatase assembled on its surface. The Zr dopant was successfully incorporated into the anatase lattice, resulting in a slight deformation of the anatase crystal and the reduction of the band gap. These materials exhibit high surface area with a disordered mesoporous structure formed by TiO2 particles (15-20nm) supported on a delaminated clay. They were tested in the solar photodegradation of antipyrine, usually used as an analgesic drug and selected as an example of emerging pollutant. High degradation rates have been obtained at low antipyrine concentrations and high solar irradiation intensities with the Zr-doped TiO2/clay catalyst, more effective than the undoped one.
4.Enantioselective analysis of 4-hydroxycyclophosphamide in human plasma with application to a clinical pharmacokinetic study.
de Castro FA1, Scatena Gdos S2, Rocha OP1, Marques MP1, Cass QB2, Simões BP3, Lanchote VL4. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Feb 1;1011:53-61. doi: 10.1016/j.jchromb.2015.12.049. Epub 2015 Dec 28.
Cyclophosphamide (CY) is one of the most common immunosuppressive agents used in autologous hematopoietic stem cell transplantation. CY is a prodrug and is metabolized to active 4-hydroxycyclophosphamide (HCY). Many authors have suggested an association between enantioselectivity in CY metabolism and treatment efficacy and/or complications. This study describes the development and validation of an analytical method of HCY enantiomers in human plasma by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) that can be applied to pharmacokinetic studies, filling this gap in the literature. HCY enantiomers previously derivatized with phenylhydrazine were extracted from 200-μL plasma aliquots spiked with antipyrine as internal standard and a mixture of hexane and dichloromethane (80:20, v/v) was used as the extraction solvent. The derivatized HCY enantiomers were resolved on a Chiracel(®) OD-R column using water:acetonitrile:formic acid (55:45:0.