Roberto Gleason

Captopril does not scavenge superoxide: captopril prevents O2-. production by chelating copper.

The purpose of this study was to use a direct method, that of electron spin resonance spectroscopy, to evaluate the ability of captopril, an angiotensin-converting enzyme inhibitor, to prevent the superoxide-mediated formation of phenyl radicals. Results indicate that, under certain conditions, captopril is a potent inhibitor of the generation of phenyl radicals, produced by the autoxidation of phenylhydrazine. The inhibitory effect of captopril, however, was better understood as a direct interaction of the drug with the metals that catalyze the autoxidation process rather than as a reaction of captopril with the free radicals generated. This last conclusion was supported by the finding that captopril was not able to inhibit the superoxide anion-mediated reduction of nitroblue tetrazolium.

Study of the interaction of cadmium with membrane-bound succinate dehydrogenase

Cadmium ions inhibit membrane-bound succinate dehydrogenase with a second-order rate constant of 10.42 mM−1s−1 at pH 7.35 and 25°C. Succinate and malonate protect the enzyme against cadmium ion inhibition. The protection pattern exerted by succinate and malonate suggests that the group modified by cadmium is located at the active site. The pH curve of inactivation by Cd2+ indicates the involvement of an amino acid residue with pKa of 7.23.

Correlation of ESR with lyoluminescence dosimetry using some sugars

Abstract Most applications involving ESR dosimetry currently center on aminoacids because of their relative tissue equivalence. Sugars, however, in addition to possessing high sensitivity and stability in their ESR and LL responses, are widely available as chemical reagents and as commercial sugar. In the present study, dosimetric characteristics of mannose, trehalose, sucrose and commercial sugar obtained by means of ESR and LL techniques are reported. Doses measured by both methods showed agreement within 5%.

Study of a Fenton type reaction: effect of captopril and chelating reagents.

The purpose of this study was to determine if captopril, an angiotensin-converting enzyme inhibitor, could interact with iron ions and so modify a Fenton type reaction. Results indicate that different degrees of thiobarbituric acid-reactive substance from deoxyribose are obtained in an ascorbate-driven Fenton system depending on the order of addition of captopril and iron to the incubation medium. Similar results were obtained with the chelating reagents ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid, indicating that the buffer solution plays a relevant role when a particular iron complex is formed with a chelating agent. These metal complexes produce oxidizing species in a Fenton type system whose nature is discussed.

EPR measurements of the spin-hamiltonian zero-field splitting parameters as a function of temperature in MN2+-doped Cs2NaLaCl6

Abstract The spin-Hamiltonian zero-field splitting parameter b 2 0 is measured as a function of temperature in Mn 2+ doped Cs 2 NaLaCl 6 single crystals (elpasolite type). The experiments showed that the Mn 2+ ion occupies two different tetragonal symmetry sites in the cubic crystalline lattice of Cs 2 NaLaCl 6 . Both sites possess principal Z-axes along 〈100〉 crystallographic directions. Electron spin resonance measurements were made at X-band frequencies (9.2 GHz) in the temperature range from 12.8 to 300 K. The present results are taken into account in order to establish a possible relation between the spin-Hamiltonian parameter b 2 0 and the temperature. A tentative determination of the Debye temperature is derived from the experimental data.

Piroxicam and meloxicam ameliorate hepatic oxidative stress and protein carbonylation in Kupffer and sinusoidal endothelial cells promoted by ischemia-reperfusion injury.

The present study was aimed to assess the effect of protein carbonylation (PC) in hepatic cells and effects of nonsteroidal anti‐inflammatory drugs (NSAIDs) on indicators of tissue damage induced by liver ischemia–reperfusion injury (LIRI). Warm ischemia was performed by partial vascular occlusion during 90 min in Wistar rats. In serum, we determined the catalytic activity of Alanine Aminotransferase, Aspartate Aminotransferase, Lacticate Dehydrogenase, and Ornithine Carbamoyltransferase. In liver samples, we studied cellular alterations by means of histologic studies, lipid peroxidation, PC by immunohistochemistry, apoptosis and reactive oxygen species in bile by electron paramagnetic resonance. Based on PC data, sinusoidal endothelial cells (SEC) and Kupffer cells (KC) were the first to exhibit LIRI‐associated oxidative damage and prior to parenchymal cells. Administration of piroxicam or meloxicam during the pre‐ischemic period produced a highly significant decrease in all studied injury indicators. No significant differences were revealed between the protective action of the two drugs. The data shown here suggest the potential use of NSAIDs such as piroxicam or meloxicam in minimizing ischemic event‐caused damage in liver. We also propose that PC may be employed as an adequate tool to assess tissue damage after oxidative stress.

Superoxide-Superoxide Oxidoreductase Activity of the Captopril-Copper Complex

BACKGROUND The purpose of this study was to determine whether the interaction of captopril, an angiotensin-converting enzyme inhibitor, with copper could modify the superoxide dismutase activity of this metal. Results may help to explain the interaction of captopril with reactive oxygen species in the stunned myocardium where substantial mobilization of copper and iron in the coronary flow following ischemia has been reported. METHODS An assay that generates superoxide anion radicals without the intervention of metal ions was utilized. In addition, direct EPR analysis was applied to assess the redox state of copper during reactions. RESULTS Captopril-copper complex inhibited the superoxide-mediated reduction of nitroblue tetrazolium. In addition, captopril-copper complex was able to suppress formazan production by potassium superoxide. Direct EPR analysis showed that copper was reduced to the cuprous state by captopril and remained in this state in the course of the reaction. Captopril was also stable during the dismutation reaction. CONCLUSIONS We conclude that cuprous-captopril complex is a catalytic species with properties different from those of Cu(2+) alone. A model in which sulfur acts as electron acceptor/donor in place of the metal is proposed and a mechanism of action for this complex is discussed.

Electron paramagnetic resonance studies of gamma-irradiated PVC at high pressure

Abstract PVC was compressed into discs with a pressure of 0-0.88 GPa and then irradiated with 200 kGy at room temperature and liquid nitrogen temperature, the polymeric radicals formed were studied by EPR spectroscopy. The radical concentration and its decay with temperature and time were investigated. The number of radicals increased with increase in pressure and decrease in temperature. The radicals produced by irradiation at atmospheric pressure had shorter half-lives than those formed for the compressed samples, and showed an asymmetric pattern of alkylperoxyl radicals. In the case of compressed samples, the formation of peroxyl radicals was not appreciable probably due to lack of oxygen diffusion. In all the cases three different radicals were formed and their half-lives were determined.