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Journal Article 2008; 29(5): 728-732 PubMed PMID: 18987592 Citation  Keywords:  Acetyl Coenzyme A:metabolism, Arylamine N-Acetyltransferase:metabolism, Arylsulfotransferase:metabolism, Autoradiography, Catalysis, DNA:chemistry, DNA Adducts:chemistry, Deoxyguanosine:chemistry, Ellipticines:chemistry, Hydrogen-Ion Concentration, Indica.   

OBJECTIVES: Ellipticine is a potent antineoplastic agent exhibiting multiple mechanisms of its action. Recently, we have found that 13-hydroxyellipticine, formed from ellipticine as the predominant metabolite in human livers, is bound to deoxyguanosine in DNA, generating the major DNA adduct in vivo and in vitro. The development of the methods suitable for the preparation of this adduct in the amounts sufficient for identification of its structure and those for its isolation and partial characterization is the aim of this study.r />r /> METHODS: High performance liquid chromatography (HPLC) was employed for separation of 13-hydroxyellipticine-mediated deoxyguanosine adduct. The 32P-postlabeling technique was utilized to detect this adduct in DNA.r />r /> RESULTS: The formation of the 13-hydroxyellipticine-derived deoxyguanosine adduct in DNA in vitro was increased under the alkaline pH of the incubations and by the formation of the sulfate and acetate conjugates of 13-hydroxyellipticine generated by reactions with 3'-phosphoadenosine-5'-phosphosulfate (PAPS) or acetyl-coenzyme A (acetyl-CoA) catalyzed by human sulfotransferases (SULTs) 1A1 and 1A2 and N,O-acetyltransferases (NATs) 1 and 2. The HPLC method suitable for separation the 13-hydroxyellipticine-derived deoxyguanosine adduct from other reactants, deoxyguanosine and 13-hydroxyellipticine, was developed. The structure of this adduct is proposed to correspond to the product formed from ellipticine-13-ylium with the exocyclic 2-NH2 group of guanine in DNA.r />r /> CONCLUSIONS: The data are the first report on HPLC isolation of the deoxyguanosine adduct formed by 13-hydroxyellipticine in DNA and its partial characterization....

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Journal Article 2008; 29(5): 675-679 PubMed PMID: 18987591 Citation  Keywords:  Adolescent, Age Factors, Animals, Child, Czech Republic:epidemiology, Dental Amalgam, Dental Restoration, Permanent, Diet, Female, Fishes:metabolism, Hair:chemistry, Humans, Male, Meat, Mercury:analysis, Poland:epidemiology, Sex Factors,.   

OBJECTIVES: Mercury and most of its compounds are extremely toxic and should be handled with care. It can be inhaled and absorbed through the skin and mucous membranes. The most toxic forms of mercury are its organic compounds such as dimethylmercury and methylmercury. Fish have a natural tendency to accumulate mercury. Methylmercury is produced by microbial methylation of inorganic mercury in water sediment then it infiltrates the food chain and it consequently accumulates in fish. Fish are the main source of methylmercury in human food. Mercury is transferred into a hair; and this can be than used to monitor the long-term exposure to mercury. The content of mercury in hair depends on the frequency of fish consumption. The aim of our study was to compare mercury content in the hair of children that had various amounts of fish consumption (increased or reduced).r />r /> DESIGN: Total mercury content in hair was determined by direct method of cold vapors using an AMA 245 analyzer. A total of 174 hair samples from the children (9-17 years old) were analyzed. In this study, the following localities were compared: Neratovice (n=42), Jeseníky (n=44), Prague (n=59) in Czech Republic and Olsztyn in Poland (n=29). Every sample was accompanied with questionnaire about age, gender, regions, amalgam fillings and fish consumption.r />r /> RESULTS: We did not find a correlation between the content of mercury in hair with age, gender or amalgam fillings. We did find a correlation between fish consumption and the amount of mercury found in the hair samples.r />r /> CONCLUSION: The amount of mercury in hair increases with more frequent consumption of freshwater and marine fish....

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Comparative Study 2008; 29(5): 755-758 PubMed PMID: 18987590 Citation  Keywords:  Acetylcholinesterase:chemistry, Algorithms, Alzheimer Disease:drug therapy, Biosensing Techniques, Cholinesterase Inhibitors:analysis, Electrochemistry, Enzymes, Immobilized:chemistry, Humans, Kinetics, Nootropic Agents:analysis, Tacrine:analogs & derivat.   

: Two drugs were tested using electrochemical biosensor with immobilized acetylcholinesterase (AChE). The first was commercialized drug tacrine (known also as Cognex) used for treatment of cognitive manifestation of Alzheimer\'s disease (AD). The second one was its 7-methoxy derivate (7-MEOTA) that has not been marketed. We determined the IC50 (6.67+/-0.92)x10-7 M for tacrine and (1.66+/-1.43)x10-9 M for 7-MEOTA. In this in vitro study, 7-MEOTA acts as stronger inhibitor of AChE and in this way could be more favorable for treatment of cognitive manifestation of AD. Our study shows that biosensor technology could be used as a quick and cheap tool for testing of promising AChE inhibitors (AD drug candidates)....

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Journal Article 2008; 29(5): 706-711 PubMed PMID: 18987589 Citation  Keywords:  Animals, Antioxidants:therapeutic use, Arthritis, Experimental:blood, Chromatography, High Pressure Liquid, Enzyme-Linked Immunosorbent Assay, Indoles:therapeutic use, Lipid Peroxidation:drug effects, Male, Mass Spectrometry, Muscle, Skeletal:drug effects.   

OBJECTIVES: To study possible oxidation of proteins and lipids in plasma and sarcoplasmic reticulum (SR) from skeletal muscles and to assess the effects of pyridoindole antioxidants in rats with adjuvant arthritis (AA) and to analyze modulation of Ca-ATPase activity from SR (SERCA).r />r /> METHODS: SR was isolated by ultracentrifugation, protein carbonyls in plasma and SR were determined by ELISA. Lipid peroxidation was analyzed by TBARS determination and by mass spectrometry. ATPase activity of SERCA was measured by NADH-coupled enzyme assay. Tryptophan fluorescence was used to analyze conformational alterations.r />r /> RESULTS: Increase of protein carbonyls and lipid peroxidation was observed in plasma of rats with adjuvant arthritis. Pyridoindole antioxidant stobadine and its methylated derivative SMe1 decreased protein carbonyl formation in plasma, effect of stobadine was significant. Lipid peroxidation of plasma was without any effect of pyridoindole derivatives. Neither protein oxidation nor lipid peroxidation was identified in SR from AA rats. SERCA activity from AA rats increased significantly, stobadine and SMe1 diminished enzyme activity. Ratio of tryptophan fluorescence intensity in SR of AA rats increased and was not influenced by antioxidants.r />r /> CONCLUSION: Plasma proteins and lipids were oxidatively injured in rats with AA; antioxidants exerted protection only with respect to proteins. In SR, SERCA activity was altered, apparently induced by its conformational changes, as supported by study of tryptophan fluorescence. Stobadine and SMe1 induced a decrease of SERCA activity, elevated in AA rats, but they did not affect conformational changes associated with tryptophan fluorescence....

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Journal Article 2008; 29(5): 649-652 PubMed PMID: 18987588 Citation  Keywords:  Animals, Antineoplastic Agents, Phytogenic:pharmacology, Antioxidants:pharmacology, Apoptosis:drug effects, Biphenyl Compounds, Chelidonium:chemistry, Dose-Response Relationship, Drug, Free Radical Scavengers, HL-60 Cells, Humans, Leukemia:drug therapy, L.   

OBJECTIVES: The purpose of this study was to assess whether a methanol extract isolated from the greater celandine Chelidonium majus L. (CME) had antioxidant effect and was able to inhibit proliferation and to induce apoptosis in leukemia cells in vitro.r />r /> METHODS: The potential antioxidant activity of CME was proved by the 1,1-diphenyl- 2-picrylhydrazyl (DPPH) radical scavenging assay. The cytotoxicity of CME was measured by the cell growth inhibition assay using murine leukemia L1210 cell line and human promyelocytic HL-60 leukemia cells. Apoptosis-inducing effect was determined by fluorescence microscopy (chromatin condensation and nuclear DNA fragmentation).r />r /> RESULTS: In the DPPH assay CME acted as a scavenger of DPPH free radical. The results on antiproliferative properties assessment clearly demonstrated that CME had a cytotoxic effect towards both leukemia cell lines in a dose-dependent manner. In addition, the human promyelocytic HL-60 cells were more sensitive to CME treatment than the L1210 cells.r />r /> CONCLUSIONS: We concluded that the extract of C. majus L. had a strong antioxidant potential and exerted the antiproliferative activity via apoptosis on leukemia cells. CME due to the presence of the isoquinoline alkaloids and the flavonoid components may play an important role in both cancer chemoprevention through its antioxidant activity and modern cancer chemotherapy as cytotoxic and apoptosis-inducing agent....

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Journal Article 2008; 29(5): 639-643 PubMed PMID: 18987587 Citation  Keywords:  Abnormalities, Drug-Induced:pathology, Animals, Antioxidants:toxicity, Female, Fetal Development:drug effects, Fetal Diseases:chemically induced, Indoles:toxicity, Neuroprotective Agents:toxicity, Pregnancy, Pyridines:toxicity, Rats, Rats, Wistar, Reprodu.   

OBJECTIVE: The 2-ethoxycarbonyl-8-methoxy-2,3,4,4a,5,9b-hexahydro-1H-pyrido-[4,3b] indolinium chloride (SMe1EC2) is a prospective antioxidant and neuroprotectant drug. The aim of the study was to evaluate the effect of SMe1EC2 on embryofetal development of rats.r />r /> METHODS: The substance tested was administered orally to Wistar/DV rats from day 6 to day 15 of gestation at the doses 5, 50 and 250 mg/kg/day. The animals were killed on day 20 of gestation and uterine content was inspected. Live fetuses were examined for gross, skeletal and visceral anomalies.r />r /> RESULTS: Administration of SMe1EC2 did not induce any signs of maternal toxicity. No adverse effect of the substance tested was found on reproductive variables. Morphological examination of fetuses revealed no evidence of teratogenesis.r />r /> CONCLUSION: The prenatal toxicity study showed that the substance SMe1EC2 tested did not have embryotoxic and teratogenic effects on developing rats. Neither were any signs of maternal toxicity found....

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Case Reports 2008; 29(5): 627-630 PubMed PMID: 18987586 Citation  Keywords:  Asphyxia Neonatorum:enzymology, Cardiopulmonary Resuscitation, Carnitine O-Palmitoyltransferase:deficiency, Heart Failure:etiology, Humans, Infant, Newborn, Male, Respiratory Insufficiency:etiology, Tandem Mass Spectrometry,.   

OBJECTIVES: To present a term newborn with severe asphyxial status due to dysrrhythmia induced by the neonatal form of carnitine palmitoyltransferase II deficiency (CPT II).r />r /> RESULTS: Term newborn delivered spontaneously (birth weight 3450 grams, birth length 52 cm, values of Apgar score 10/10) with good direct adaptation, on second day of life he manifested severe asphyxial status followed by cardiorespiratory insufficiency with circulatory failure. After prolonged resuscitation of 3 hours, the child was admitted to our neonatological department. Diagnosis of CPT II was confirmed (free carnitine level in blood 12.2 micromol/l; ratio (C16+C18):1/C2 was 0.760 by tandem mass spectrometry; activity of CPT II in leukocytes was 0.082 micromol/min x gram protein). After appropriate treatment the patient survived the critical period.r />r /> CONCLUSIONS: Neonatal form of CPT II deficiency is the most severe form and is considered to be invariably fatal. This kind of metabolic disease is congenital, but cardiac problems are not detectable during the prenatal period. Fasting in the early newborn period is a main trigger of CPT II deficiency signs. The authors emphasise the relevance of investigating acylcarnitine profiles and carnitine in serum in all cases of severe postnatal asphyxia and in cases of unusual newborn arrhythmias since some forms of disturbances in beta oxidation of fatty acids are partially treatable....

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Journal Article 2008; 29(5): 609-613 PubMed PMID: 18987585 Citation  Keywords:  Animals, Antioxidants:pharmacology, Drug-Related Side Effects and Adverse Reactions, Herbicides:toxicity, Humans, Melatonin:pharmacology, Metals:toxicity, Neurotoxins:toxicity, Oxidative Stress:drug effects, Prescription Drugs:toxicity, Reactive Nitrogen .   

: The purpose of this brief review is to introduce the reader to the vast amount of published literature related to the free radical scavenging and antioxidative activity of melatonin. However, this review summarizes only a few of the many conditions in which melatonin has been found to be protective against oxidative/nitrosative damage. Melatonin ameliorates the extensive free radical-mediated damage that ensues following exposure to a wide variety of environmental insults. Concisely reviewed in this report are the protective effects of melatonin against toxic prescription drugs, neural toxins, herbicides and metals. The findings have clear implications for the utility of melatonin in toxicology....

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