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L G Korkina

Publications and source records attributed to L G Korkina.

At least 19 recordsLinked to original sources
PubMed1996

Cytogenetic, developmental, and biochemical effects of aluminum, iron, and their mixture in sea urchins and mussels.

The present study was undertaken to evaluate the toxicity of aluminum sulfate, ferric chloride and their 1:1 mixture (Mix) on early development, fertilization and offspring quality in three sea urchins species (Sphaerechinus granularis, Paracentrotus lividus, Psammechinus microtuberculatus) and in mussels (Mytilus galloprovincialis). The endpoints were the following: a) larval malformations; b) developmental arrest; c) embryonic mortality; d) fertilization success; e) cytogenetic effects, and f) luminol-dependent chemiluminescence (LDCL). Overall data point to the induction of developmental defects in both sea urchin and mussel embryos following exposure of embryos to Al(III) or Fe(III) (10(-7) to 10(-6) M), whereas Mix caused varied effects vs. Al(III) or Fe(III) alone, from scarce or no additive effects (M. galloprovincialis and P. lividus) to a dramatic rise in embryolethality even at nominal levels of 10(-8) M (Ps. microtuberculatus).S. granularis sperm underwent a dose-dependent decrease in fertilization success following exposure to Al(III), or Fe(III), or Mix at levels ranging from 10(-8) to 10(-5) M. A significant increase of developmental defects was observed in the offspring of S. granularis sperm exposed to micromolar levels of the agents, suggesting an Al(III)- and Fe(III)-related transmissible damage to sperm. The cytogenetic analysis of Al(III)-, Fe(III)-, or Mix-exposed S. granularis embryos showed a significant increase in mitotic aberrations. A relevant feature of the observed cytogenetic damage included scattered chromosomes, suggesting cytoskeleton damage. The LDCL emission in S. granularis embryos showed a dose-related inhibition by agent levels ranging from 10(-7) to 10(-5) M; this held true for both spontaneous and, to a larger extent, for horseradish peroxidase (HRP)-activated LDCL. LDCL associated with fertilization was affected by Al(III), Fe(III) and Mix, with a time- and dose-related shift from stimulation to inhibition. The changes observed in LDCL emission suggested that the observed damage to embryogenesis, fertilization and mitotic activity may be related, at least partly, to alterations of the embryo prooxidant state. The present data point to developmental, cytogenetic and biochemical changes related to realistic levels of Al(III), Fe(III) and their mixtures, raising concern as to their environmental, occupational and iatrogenic exposures.

Alum Compounds↗
PubMed1995

Different antioxidant activities of bioflavonoid rutin in normal and iron-overloading rats.

The effects of rutin on liver microsomes, peritoneal macrophages, and blood neutrophils isolated from iron-overloading (IOL) and normal rats were studied. The formation of 2-thiobarbituric acid-reactive products and the level of lucigenin-amplified chemiluminescence (CL) were determined in liver microsomes. Oxygen radical production by phagocytes was measured by luminol- and lucigenin-amplified CL and superoxide dismutase-sensitive cytochrome c reduction. These ex vivo findings were compared with the in vitro effects of rutin on cellular free processes. It was found that rutin administration sharply suppressed free radical production in liver microsomes and by phagocytes of IOL animals and only slightly affected these processes in normal rats. The selective inhibitory effect of rutin under pathologic conditions induced by iron overload is thought to be due to the formation of inactive iron-rutin complexes which are unable to catalyse the conversion of superoxide ion into reactive hydroxyl radicals, a process responsible for the free radical-mediated toxic effects of iron overload. These findings may account for the favourable effects of the treatment of pathologies associated with iron overload with rutin.

Acridines↗
PubMed1995

A possible interaction between acetylcholinesterase and dopamine molecules during autoxidation of the amine.

Acetylcholinesterase has an action in the central nervous system, independent of hydrolysis of acetylcholine. This study explored the possible interaction between the two molecules: the effects of acetylcholinesterase on the autoxidation of the catecholamine were tested, and, in turn, modification of the catalytic activity of the enzyme by products of dopamine oxidation were studied. Acetylcholinesterase selectively inhibited the speed of quinone production from dopamine as well as accumulation of hydrogen peroxide, whilst the rate of generation of superoxide was increased. Analysis of absorption spectra revealed the formation of a new product, which appeared after mixing acetylcholinesterase and dopamine in neutral pH. In all cases, butyrylcholinesterase was ineffective. Incubation of acetylcholinesterase in the presence of dopamine resulted in a significant decrease in the catalytic activity of the enzyme. The effects of application of preparations modifying autoxidation of dopamine (SOD, catalase, peroxidase) suggested that inactivation of the enzyme occurred as a result of the direct interaction of a quinone and/or semiquinone oxidation product with enzyme, as opposed to any effects of reactive oxygen species. Because acetylcholinesterase and dopamine are co-released from the neurons degenerating in Parkinson's disease, a direct chemical interaction between these two molecules could have significance both for the normal functioning of the substantia nigra and for related pathological states.

Acetylcholinesterase↗
PubMed1995

Autoxidation of dopamine: a comparison of luminescent and spectrophotometric detection in basic solutions.

Oxidation products of catecholamines, particularly dopamine, could play an important role in the physiology and pathology of the nervous system. This study has therefore characterised autoxidation of dopamine monitored in a variety of systems. Lucigenin-dependent chemiluminescence and reduction of cytochrome c were exploited to register generation of the byproduct superoxide anion, whereas the quinone product was detected by a direct spectrophotometric measurement. Accumulation of hydrogen peroxide was followed as an increase in luminol-dependent chemiluminescence. In all cases, basic solutions were used to initiate the oxidation of dopamine. The results obtained could be interpreted as specific reactions at the particular stages of the autoxidation process: the luminol-dependent chemiluminescence system detected accumulation of hydrogen peroxide during dopamine oxidation, whereas the lucigenin-dependent chemiluminescence indicated generation of superoxide anion. Furthermore, cytochrome c reduction, observed during dopamine oxidation, was probably attributed to a direct interaction with dopamine semiquinone. In addition, the effects of superoxide dismutase, catalase, and peroxidase were examined in each of the systems: Each enzyme exhibited a different effect in each system used. The possible reaction mechanisms leading to different action of enzymes affecting reactive oxygen species are discussed. The methods described here of monitoring dopamine autoxidation could thus be used in parallel to detect the effects of different preparations on various stages of the dopamine autoxidation process.

Acridines↗
PubMed1995

Study of antioxidant properties of metal aspartates.

The effects of Zn, Mg, Cr, Cu, and Mn aspartates, their commercial formulation Inzolen, and the individual commercial medicine Unizinc, on oxygen radical production by enzymes [xanthine oxidase, horseradish peroxidase, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase] and phagocytic cells (human blood leukocytes) have been studied. The formation of oxygen radicals was measured by luminol- and lucigenin-amplified chemiluminescence and by the reduction of cytochrome c. All these compounds (excluding Cr aspartate) turn out to be inhibitors of oxygen radical formation in the systems studied (excluding horseradish peroxidase). Their inhibitory activities were a consequence of both the scavenging of free radicals and the inhibition of xanthine oxidase and NADPH oxidase activities. As expected, the most active free-radical scavengers were transition metal Cu and Mn aspartates, which mimicked the activities of copper-zinc and manganese dismutases. However, surprisingly non-transition metal Zn and Mg aspartates were also able to scavenge oxygen radicals. It was suggested that the scavenging activities of Zn and Mg aspartates may be explained by affecting the rate of spontaneous dismutation of the superoxide ion. In addition, it was found that Zn aspartate is an efficient inhibitor of the formation of the most reactive hydroxyl radicals. These antioxidant properties of Zn aspartate make it important in medicine for the prevention and treatment of free radical pathologies.

Antioxidants↗
PubMed1995

In vivo accumulation of 8-hydroxy-2'-deoxyguanosine in DNA correlates with release of reactive oxygen species in Fanconi's anaemia families.

The present study was aimed at verifying the occurrence, if any, of in vivo oxidative DNA damage in FA homozygotes, their parents and siblings. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) was measured, by HPLC/EC, in DNA from circulating blood leucocytes from FA homozygotes and their relatives and compared with a group of paediatric and adult healthy subjects. The population studied consisted of: (i) 15 FA homozygotes; (ii) 24 FA heterozygotes; (iii) 11 siblings. The 8-OHdG level in FA homozygotes was significantly higher with respect to age-matched controls, with a mean level of 33.3 +/- 6.8 (mean +/- SE) and 3.9 +/- 0.26 8-OHdG/10(5) dG respectively. The FA parents (heterozygotes) also displayed higher 8-OHdG levels relative to controls. The release of hydroxyl (.OH) and .OH-like radicals from leucocytes was determined by luminol-dependent chemiluminescence (LDCL) in a subgroup of FA homo- and heterozygotes, showing a very large in vivo formation of non-superoxide radicals. Chromosomal instability was also measured in the FA population. When relating either 8-OHdG or LDCL levels to spontaneous or diepoxybutane-induced chromosomal instability (S-CI and DEB-CI respectively), a significant correlation was observed between the 8-OHdG, LDCL and S-CI data. Within families a positive association was found between 8-OHdG levels in homozygotes and their related heterozygotes, suggesting segregation of the genetic defect(s) underlying the abnormal oxidative metabolism. The present study provides evidence for an in vivo pro-oxidant state in FA, in terms of excess formation of .OH and .OH-like radicals, and of DNA hydroxyl adducts. This finding appears to be shared by homozygotes and, to a lesser extent, by heterozygotes.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1994

Free radical generation during interaction of chrysotile asbestos with natural compounds.

Free radical generation was found after the addition of some natural biological substances (adrenaline, ascorbate, ubiquinone Q9, etc.) to a chrysotile asbestos suspension. This was detected by the chemiluminescent method with lucigenin as an indicator. The detailed study of the chemiluminescent reaction in the adrenaline-chrysotile system indicated that the reaction required hydroxyl ions, which arose in the chrysotile suspension, and was accompanied by a superoxide radical formation. At the same time, the radical production was very low in suspensions of amphybole asbestos, talc, and quartz, which could not alkalinize the water medium. On the basis of these results, it may be concluded that chrysotile has a unique ability to generate free radicals upon interaction with some biological molecules in a water medium. This fact may explain the great carcinogenicity of chrysotile. The injection of cigarette smoke solution into chrysotile (but not into amphibole asbestos or talc) suspension induced intensive chemiluminescence. This suggests that smoke aggravates the effect of chrysotile on human health by increasing free radical generation on the surface of the fibers.

Asbestos, Amphibole↗
PubMed1994

[Chemiluminescent determination of superoxide dismutase activity].

A specific chemiluminescent method for the assessment of superoxide dismutase (SOD) activity in human blood has been developed. Intensive lucinogen-dependent chemiluminescence was observed during adrenalin oxidation in alkaline medium, and the level of this chemiluminescence essentially decreased in the presence of SOD. 50% inhibition of chemiluminescence was observed in the presence of 25 ng/ml of the enzyme, this indicating a high sensitivity of the method as against a similar spectrophotometric technique. SOD activities in donor blood samples were measured. The described method is offered for clinical application.

Humans↗
PubMed1994

[Use of the fluorescent indicator hydroethidine to study the oxidative metabolism of phagocytes].

Hydroethidene was found to interact with O2-. in a 1:1 molar ratio. This property may be used for measuring O2-. radicals in the systems generating exclusively superoxide radicals or to single out the superoxide-sensitive part of the reaction by introducing superoxide dismutase into the system. Hydroethidene permits analysis of endogenous and total APK production and helps obtain more complete information on the site and trends of APK generation. Use of this reagents seems to be promising in assessment of mitochondrial function in situ without preliminary isolation thereof, as well as of microsomal cytochrome P-450 containing monoxygenase system.

Animals↗
PubMed1993

Is superoxide an initiator of microsomal lipid peroxidation?

The effects of "pro-oxidant" quinones, doxorubicin, Fe(3+)-ADP-doxorubicin complex, and menadione, as well as of free radical scavengers possessing superoxide-dismuting activities, Fe(3+)-rutin and Cu(2+)-rutin, on superoxide production and lipid peroxidation in rat liver microsomes have been studied. All quinone compounds efficiently suppressed lucigenin-dependent chemiluminescence produced in NADPH-dependent microsomal lipid peroxidation, but exhibited different effects on cytochrome c reduction: doxorubicin and Fe(3+)-ADP-doxorubicin weakly inhibited and menadione enhanced it. In accord with previous findings, menadione inhibited malondialdehyde (MDA) formation in microsomes, while Fe3-ADP-doxorubicin enhanced it. Efficiency of inhibition of MDA formation by the Fe(3+)-rutin and Cu(2+)-rutin complexes correlated well with their superoxide-dismuting activities in contrast to the findings obtained in nonenzymatic liposomal peroxidation, where the formation of superoxide ion is not expected. On these grounds, we propose that superoxide ion is an obligatory initiation species in microsomal lipid peroxidation; the effects of pro-oxidant quinones on lipid peroxidation depends on their ability to chelate iron ions and not on their redox-cycling activities.

Acridines↗
PubMed1993

Peculiarities of the clastogenic properties of chrysotile-asbestos fibers and zeolite particles.

It has been established that chrysotile-asbestos fibers and zeolite particles induce chromosome aberrations in human lymphocytes from whole blood cultures, peritoneal fluid cells and bone marrow cells of mice. It is shown that the level of cytogenetic response from the intraperitoneal administration of chrysotile-asbestos fibers and zeolite particles depends on the time of their exposure. Further, it is shown that SOD eliminates the cytogenetic effect of chrysotile-asbestos fibers, while catalase inhibits that of zeolite particles. Recommendations concerning testing for the mutagenic properties of mineral fibers and particles are given, and possible mechanisms of their damaging effects are discussed.

Animals↗
PubMed1993

[Remote effects in the mutagenic action of chrysotile asbestos and zeolite dusts in vivo].

It was proposed that there are a generalized mutagenic actions of chrysotile-asbestos fibers and zeolite particles in vivo. Chrysotile-asbestos fibers and different species zeolite particles in doses 50 mg/kg, intraperitoneally, increased the levels of damaged chromosomes not only in peritoneal cells, but also in bone marrow of C57BL/6 mice. Cytogenetic effect of chrysotile-asbestos does not depends on the time exposure of animals with mutagenic factor. In four weeks followed after administration chrysotile-asbestos fibers there were revealed 19-22% peritoneal cells with damaged chromosomes and 3.2-4.4% aberrant cells of bone marrow. Cytogenetic effect of zeolite particles was observed on 14-28 days after the administration, with peaks at 35.6% in peritoneal and 3.6-4.2% in bone marrow cells. Our data indicate the mutagenic action is realised as in cells contacted with dusts as in cells of other tissues. Probably, these effects are mediated by products of lipid peroxidation.

Animals↗
PubMed1992

Release of active oxygen radicals by leukocytes of Fanconi anemia patients.

The release of oxygen radicals by blood and bone marrow leukocytes of patients with Fanconi anemia (FA) has been studied. It was found that the nonstimulated FA leukocytes and those stimulated by concanavalin A, SiO2, latex, and opsonized zymosan produced enhanced levels of luminol- and lucigenin-dependent chemiluminescence (CL) in comparison with normal leukocytes. At the same time, the ratio of the intensity of lucigenin-dependent CL to that of luminol-dependent CL was significantly smaller for FA leukocytes than for normal leukocytes. From these findings and from the effects of antioxidative enzymes and free radical scavengers on CL, it was concluded that FA leukocytes release enhanced amounts of oxygen radicals and that these free radicals contain enhanced amounts of hydroxyl or hydroxyl-like radicals more active than superoxide ion. It was proposed that elevated reactivity of the oxygen radicals released by FA leukocytes may be a major factor in the development of Fanconi anemia; this proposal is supported by the first positive results of treatment of FA patients with rutin (a nontoxic natural free radical scavenger and chelator).

Acridines↗