Sensitization of the radiation-induced chain oxidation of aromatic amines in polymer films (038)
NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS
Authors: Kolninov, OV; Kolesnikova, VV; Podsobljaev, A; Shelukhov, IP
Abstract
The sensitization of the chain redox reaction in gamma-irradiated solid films of poly(vinyl chloride) (PVC), containing N,N,N',N'-tetramethyl-4,4'-diaminodiphenylmethane (Am), CBr4 and naphthalene, was investigated by the electron spin resonance and optical spectroscopy methods. The ESR spectra of the gamma-irradiated PVC films at 77 K with the additives of Am, CBr4 and naphthalene were studied. The effects of radiation dose and annealing temperature on the transformation radicals were investigated. The spectra of radicals, taking part in the chain reaction, were separated and identified. The radiation-chemical yields of these radicals and their thermal stability were determined. The dependencies of radical concentration on the annealing temperature for samples in the presence and in absence of naphthalene were compared. It was established that the addition of naphthalene up to 0.2 kmol/m(3) results in an increase of the chain reaction yield from 80 to 150 particle/100 eV in the case if the samples are irradiated at 300 K. If the irradiation is made at 77 K, the yield of oxidized amine Am+ after annealing at 293 K rises from 20 to 45 particle/100 eV as a result of action of naphthalene. The analysis of ESR spectra, made by a computer subtraction, showed that the radiation-chemical yield of free radicals Am-., initiating the chain reaction, is not changed in consequence of the addition of naphthalene. Therefore we suggest that the sensitizing activity of naphthalene is caused by increasing the polymer chain flexibility and, consequently, the diffusion coefficient of active CBr3. radicals, the chain propagating species. (C) 2003 Elsevier B.V. All rights reserved.
The role of carbonyl reducing enzymes in oxcarbazepine in vitro metabolism in man
CHEMICO-BIOLOGICAL INTERACTIONS
Authors: Malatkova, Petra; Havlikova, Lucie; Wsol, Vladimir
Abstract
Oxcarbazepine, a second generation antiepileptic drug belonging to the family of dibenz[b,f] azepines, is subjected to a rapid and extensive biotransformation. Oxcarbazepine demonstrates a low potential for drug interactions because its biotransformation is mainly mediated by the reduction pathway instead of oxidative pathways, which are very susceptible to drug interactions. The reductive metabolism of oxcarbazepine yields a 10-monohydroxy derivative (10,11-dihydro-10-hydroxy-carbazepine), which is responsible for the pharmacological activity. The identity and localization of enzymes participating in the reduction of oxcarbazepine in response to this active metabolite have remained unknown until now. Thus, we investigated the reductive metabolism of oxcarbazepine in human liver subcellular fractions and using recombinant carbonyl reducing enzymes. The reduction of oxcarbazepine was shown to occur largely in the liver cytosol rather than liver microsomes. Furthermore, the activity and stereospecificity of cytosolic carbonyl reducing enzymes toward oxcarbazepine were assessed. Of the eight tested enzymes, six reductases were identified to contribute to the reduction of oxcarbazepine. The highest activities were demonstrated by AKR1C1, AKR1C2, AKR1C3, and AKR1C4. The contribution of CBR1 and CBR3 to the reduction of oxcarbazepine was also significant, although their role in oxcarbazepine metabolism in vivo is unclear. (C) 2014 Elsevier Ireland Ltd. All rights reserved.