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Comparative Study 2006; 27(Suppl 2): 31-34 PubMed PMID: 17159774 Citation  Keywords:  Hyaluronic Acid:chemistry, Hydrogen Peroxide:pharmacology, Manganese Compounds:pharmacology, Models, Biological, Molecular Weight, Oxides:pharmacology, Peroxynitrous Acid:chemical synthesis, Viscosity,.   

OBJECTIVES: This contribution presents the results of the kinetics of HA degradation by peroxynitrite, which represents one of the main reactive oxygen species degrading various biomacromolecules under inflammatory conditions.r />r /> METHODS: Two simple procedures have been adapted to prepare sodium peroxynitrite: the first containing an excess of H(2)O(2), and the second in which the H(2)O(2) excess had been decomposed by MnO(2) treatment. The kinetics of hyaluronan degradation by action of peroxynitrite was monitored by rotational viscometry.r />r /> RESULTS: High-molecular-weight hyaluronan was degraded by peroxynitrite. The degradation was increased in the presence of ONOO(-) previously treated by MnO(2) in order to remove residual hydrogen peroxide. One of the reasons of this finding could be that by the action of the residual metal the pathway of ONOO(-) decomposition starts to be manifested immediately on mixing traces of metals originally present in the HA sample with the ions of manganese.r />r /> CONCLUSIONS: Trace amounts of transition metal(s) should be taken into consideration on evaluating the experimental results. Purchase of the marketed peroxynitrite product appears to be the appropriate approach to simplify and standardize the quality of ONOONa....

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Journal Article 2006; 27(Suppl 2): 27-30 PubMed PMID: 17159773 Citation  Keywords:  Adenine:analogs & derivatives, Bacteria:ultrastructure, Cell Membrane:metabolism, Cytochrome P-450 Enzyme System:genetics, Drug Interactions, Humans, Liver:drug effects, Metabolic Detoxication, Phase I, Models, Biological, NADPH-Ferrihemoprotein Reductase.   

OBJECTIVES: To determine a possible influence of acyclic nucleoside phosphonates on FMO3 and CYP activity at molecular level in vitro.r />r /> METHODS: Inhibition of individual CYP and FMO3 activities in the reconstituted system and in artificial membranes (bactosomes) was studied.r />r /> RESULTS: Activity of FMO3 was inhibited by PMPA and bisPOC-PMPA even at low levels of these drugs (below 100 microM). In reconstituted system with CYP2C9, no inhibition of CYP2C9 activity was observed. On the other hand, experiments based on membrane coexpressed system showed a modest extent of inhibition (for PMEA, PMPA, bisPOM-PMEA and bisPOC-PMPA the level of inhibition was 77.8%; 74.1%; 64.2% and 68.6%, respectively at 400 microM).r />r /> CONCLUSIONS: PMPA and bisPOC-PMPA are able to inhibit FMO3 activity at relatively low levels (10-100 microM) indicating a relatively specific interaction. Activity of CYP2C9 was affected when using the membranes coexpressed with NADPHcytochrome P450 reductase. This is probably due to more natural conditions for maintaining the CYP activity in bacterial membranes. As the inhibitor concentration in the systemic circulation does not exceed 2 microM, the probability of a significant in vivo effect of adefovir, tenofovir and the respective prodrugs on the microsomal system of cytochromes P450 and FMO3 is relatively low....

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Evaluation Studies 2006; 27(Suppl 2): 23-26 PubMed PMID: 17159772 Citation  Keywords:  Animals, Antioxidants:analysis, Body Weight:drug effects, Bronchoalveolar Lavage Fluid:chemistry, Ceramics:toxicity, Glutathione Peroxidase:analysis, Inhalation Exposure:analysis, Lung:chemistry, Lung Diseases:chemically induced, Male, Mineral Fibers:toxi.   

OBJECTIVES: The programmes of asbestos replacement brought the need to use other fibres for insulation or reinforcement of material. The aim of the presented study was to follow the effect of refractory ceramic fibres (RCF3) alone or in combination with cigarette smoke (CS) on antioxidant status of the lung in experiment on animals. As free radicals are supposed to play a role in pathogenesis of lung diseases and the toxicity of particles has been associated with production of reactive oxygen species, the antioxidant status may serve as marker of lung injury. Our hypothesis was that the effect of combined exposure to RCF3 and CS will be additive or synergic.r />r /> DESIGN: Scheme of experiment: Wistar rats were randomly divided into 4 groups per 6 animals: control, intratracheal exposure to 4 mg of RCF3, inhalatory exposure to mainstream of cigarette smoke from 8 standard research 1R1 cigarettes per day, and both intratracheal exposure to RCF3 and inhalatory to CS. The exposure lasted 6 months, the inhalatory exposure was performed 5 times per week. After finishing the exposure bronchoalveolar lavage of lungs was performed and ascorbic acid, superoxide dismutase, glutathione and glutathione peroxidase were determined in lung tissue and cell free fraction of bronchoalveolar lavage fluid (BALF).r />r /> RESULTS: The results showed that the most sensitive indicator of changes in antioxidant status was glutathione, which was changed in all groups both in BALF and lung tissue homogenate....

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Evaluation Studies 2006; 27(Suppl 2): 18-22 PubMed PMID: 17159771 Citation  Keywords:  Animals, Antineoplastic Agents:pharmacokinetics, Cytochrome P-450 Enzyme System:chemistry, DNA Adducts:metabolism, Ellipticines:pharmacokinetics, Metabolic Detoxication, Phase I, Microsomes, Liver:chemistry, Models, Biological, NADP:chemistry, NADPH-Ferri.   

OBJECTIVES: Ellipticine is a potent antineoplastic agent exhibiting multiple action mechanisms. Recently, we found that after cytochrome P450 (CYP)-mediated oxidation ellipticine forms covalent DNA adducts. Ellipticine oxidation by isolated CYP and its binding to DNA is the target of this study.r />r /> METHODS: High performance liquid chromatography (HPLC) was employed for separation and characterization of ellipticine metabolites generated by CYPs. The (32)P-postlabeling technique was utilized to determine ellipticine-DNA adducts.r />r /> RESULTS: Purified CYP enzymes reconstituted with NADPH:CYP reductase oxidized ellipticine to up to five metabolites, 7-hydroxy-, 9-hydroxy-, 12-hydroxy-, 13-hydroxyellipticine and ellipticine N(2)-oxide. However, only CYP1A1 was capable to form all metabolites. Using the reconstituted enzymatic system, we demonstrated that the detoxication ellipticine metabolites, 7-hydroxyellipticine and 9-hydroxyellipticine, are mainly generated by CYP1A1 and 1A2, while those responsible for DNA binding, 13-hydroxy-, 12-hydroxyellipticine and ellipticine N(2)-oxide, by CYP3A1 and 2C3. Likewise, the most efficient CYPs forming DNA adducts from ellipticine were CYP3A1 and 2C3.r />r /> CONCLUSIONS: The results showed that the system of purified CYPs reconstituted with NADPH: CYP reductase proved for ellipticine oxidation provide a true reflection of the situation in the microsomal membrane....

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Journal Article 2006; 27(Suppl 2): 14-17 PubMed PMID: 17159770 Citation  Keywords:  Adenine:metabolism, Animals, Colon:drug effects, Cytochrome P-450 CYP1A1:metabolism, DNA, Single-Stranded:metabolism, Electrochemistry, Enzyme Activation:drug effects, Flavonoids:metabolism, Guanidine:metabolism, Male, Microsomes, Liver:drug effects, Mode.   

OBJECTIVES: Flavonoids are widely accepted as health promoting phytochemicals, however, some flavonoids show ability of direct interaction with DNA and/or enhance carcinogen activation into DNA modifying agents. Thus, their potential harmful effect on the human body should be examined in detail.r />r /> METHODS: Direct interaction of flavonoids (quercetin, rutin) with DNA was examined using square wave voltammetry on carbon paste electrode. Induction effect of selected flavonoids on content of cytochrome P450 1A1, carcinogens activating enzyme, in colon and liver microsomal samples of animals exposed to flavonoids was determined by Western blotting, using anti-cytochrome P450 1A1 specific antibody.r />r /> RESULTS: Of the natural flavonoids tested, induction of CYP1A1 was elicited by the typical citrus flavonoid naringenin in the colon, as well as by flavone in the liver. Moreover, synthetic beta-naphthoflavone and naturally occurring chrysin, quercetin and diosmin induced CYP1A1 in both tissues. The oxidation signals of guanine and adenine in the DNA molecule were decreased in the presence of flavonoids.r />r /> CONCLUSIONS: Although flavonoids are often considered to be safe because of their "plant origin", ingestion of flavonoids should be taken with caution. Enhanced expression of CYP1A1 in colon tissue might be responsible for increasing incidence of colorectal carcinoma in humans. Electrochemistry can be used to study the interactions of flavonoids and DNA....

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Journal Article 2006; 27(Suppl 2): 9-13 PubMed PMID: 17159769 Citation  Keywords:  Adolescent, Adult, Aged, Aniline Compounds:metabolism, Animals, Anisoles:pharmacokinetics, Carcinogens:pharmacokinetics, Child, Child, Preschool, Cytochrome P-450 Enzyme System:metabolism, Female, Humans, In Vitro Techniques, Male, Metabolic Detoxication,.   

OBJECTIVES: The detoxifying metabolism of a potent rodent carcinogen, 2-nitroanisole (2-NA) by human, rabbit and rat cytochromes P450 (P450) was investigated. Comparison between P450s of experimental animals and humans is essential for the extrapolation of animal carcinogenicity data to the human situation and to assess health risk.r />r /> METHODS: HPLC with UV detection was employed for the separation and characterization of 2-NA metabolites formed by hepatic microsomes, human recombinant P450s and purified rat and rabbit P450s.r />r /> RESULTS: An O-demethylated metabolite of 2-NA, 2-nitrophenol (2-NP), and two oxidation products of this metabolite [2,5-dihydroxynitrobenzene (2,5-DNB) and 2,6-dihydroxynitrobenzene (2,6-DNB)] were generated by microsomes and P450s from the species investigated, but at different levels. All the metabolites are detoxication products. 2-NP is the major metabolite generated by rabbit and rat microsomes, but 2,5-DNB is the predominant product in human microsomes. Using human recombinant P450s and purified rodent P450s, we found that human P450 2E1, 1A1 and 2B6 as well as orthologous animal P450s were the most efficient enzymes oxidizing 2-NA to 2-NP, while P450 2E1 and 1A1 were the most effective in the formation of 2,5-DNB and 2,6-DNB. In human hepatic microsomes, 2-NA was oxidized mainly by P4502E1. 2-NA and its reductive metabolite o-anisidine induced rat hepatic and renal P450 1A1/2 and NAD(P)H:quinone oxidoreductase (NQO1), thus modifying their own detoxication and/or activation pathways.r />r /> CONCLUSIONS: The data demonstrated the participation of orthologous P450s in 2-NA oxidation by all species and indicated that the rat and rabbit might serve as suitable models to mimic 2-NA oxidation in man....

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Journal Article 2006; 27(Suppl 1): 61-68 PubMed PMID: 16892010 Citation  Keywords:  Adult, Aged, Chronic Disease, Corrosion, Dental Alloys:adverse effects, Electron Probe Microanalysis, Female, Gingiva:drug effects, Humans, Hypersensitivity:etiology, Lymphocyte Activation, Male, Metals:adverse effects, Middle Aged, Mouth Mucosa:drug effe.   

OBJECTIVE: Corrosion products of different metallic alloys used in prosthetic dentistry often cause the development of a bluish-grey pigmentation of gingiva and oral mucosa. The aim of this study was to determine the content of metals in metallic pigmentations and evaluate the immune response to metals found in the oral cavity.r />r /> MATERIAL AND METHODS: The local tissue reactions were investigated clinically by electron microscopy and by energy dispersive x-ray microanalysis. An extensive anamnesis of the patients was recorded as well as earlier contacts with health care institutions. The immunological response to metallic components of dental alloys was evaluated in 34 patients by MELISA, a modified test for lymphocyte proliferation. In addition, cytokines in culture media were determined in 10 persons by the Human Inflammation Antibody Array.r />r /> RESULTS: Dense particles containing metals were found in the matrix among collagen fibrils and in close proximity of the lamina basalis of the gingival epithelium. Particles were also localized intracellularly in fibroblasts, macrophages, and endothelial cells. Metallic depositions consisted predominantly of silver accompanied by selenium and sulphur. Twenty five out of 34 patients revealed high lymphocyte reactivity (positive MELISA test) to one or more metal components of dental restorations. A correlation between the positivity in MELISA test and number of dental alloys in the oral cavity was also found. Twenty MELISA positive patients suffered from serious health problems (various allergies, autoimmune diseases, Parkinson's syndrome etc.). Nickel and inorganic mercury were the most common sensitizers in vitro. The cytokine assay revealed that mercury chloride activated predominantly TH2 lymphocytes, while nickel chloride activated mainly TH1 lymphocytes.r />r /> CONCLUSIONS: Metallic pigmentations in the oral cavity demonstrate a corrosion process and may pose a risk in immunologically susceptible patients....

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Clinical Trial 2006; 27(Suppl 1): 69-72 PubMed PMID: 16892009 Citation  Keywords:  Dental Implantation, Endosseous, Dental Implants:adverse effects, Humans, Hypersensitivity:prevention & control, Materials Testing, Treatment Outcome, Zirconium,.   

: Titanium dental implants have been used successfully in implantology for more than 40 years. Recent research, however, suggests that titanium might have more side effects than previously believed. Zirconia ceramics have been employed in orthopaedic surgery for approximately 30 years and were recently introduced into dentistry as a metal replacement for crown and bridge work as well as implant abutments. Zirconium dioxide has been shown in both in vitro and in vivo studies to have desirable osseointegrative properties. This clinical study shows that dental implants made from zirconia are a feasible alternative to titanium dental implants. In addition to excellent cosmetic results, zirconia implants allow a degree of osseointegration and soft tissue response that is superior to titanium dental implants....

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