Vojenské Zdravotnické Listy, 2001 (vol. 70), Suppl.2
THE 6th CZECH AND SLOVAK INTERNATIONAL TOXICOLOGICAL CONFERENCE IN HRADEC KRÁLOVÉ FROM 3rd TO 5th SEPTEMBER 2001
Josef Fusek
MMSL 2001, 70(S2):53
This number of Suplementum contains further papers Of the 6th Czech and Slovak International Toxicological Conference held 3-5 September 2001 at the Purkyně Military Medical Academy in Hradec Králové. This conference was held by the Toxicological Section of the Czech Association for Experimental and Clinical Pharmacology and Toxicology of the Czech Purkyně Medical Association, the Toxicological Section of the Slovak Pharmacological Association, the Slovak Medical Association and the Purkyně Military Medical Academy in Hradec Králové....
THE LONG-TERM HEALTH CONSEQUENCES OF AGENT ORANGE IN VIETNAM
G. Sofronov, V. Roumak, N. Q. AN, S. Poznyakov, N. Oumnova
MMSL 2001, 70(S2):54-69
This paper concerns the results of the 12-years prospective scientific and practical researches on the problem of the Long-Term Health Consequences (LTHC) of exposure to dioxins. The results were obtained while solving the tasks of revealing, characterizing and identification of the LTHC of the war chemicals application in Vietnam, and the most prominent of them is “Agent Orange” (AO) — the dioxin—contaminated phytotoxicant used by the US Army during the 2nd Indochina War [IOM, 1994].
REPRODUCTION TOXICITY SCREENING TEST OF THE VULM 1457 SUBSTANCE
Irina Sadloňová, Eduard Ujházy, Michal Dubovický, Eva Flaškárová
MMSL 2001, 70(S2):70
The OECD 421 (1995) Reproduction/Development Toxicity Screening Test was used in preclinical screening of toxicity of the VULM 1457 original hypolipidemic from the group of ACAT inhibitors. The purpose of the test was to collect information on the effect of the substance on basic reproductive performance of male and female rats, and, in case of positive toxicity findings, to establish the region of adverse effects.
VARIABLES OF OXIDATIVE STRESS IN PRE- AND PERINATAL DEVELOPMENT OF THE RAT
Jana Navarová, Růžena Sotníková, Mojmír Mach, Eduard Ujházy, Vladimír Knezl, Pavel Blažíček, Michal Dubovický
MMSL 2001, 70(S2):71-74
The aim of the study was to evaluate models for studying possible preventive effects of selective antioxidants on biochemical changes induced by chronic intrauterine hypoxia and neonatal anoxia in Wistar//DV rats. Anoxia of newborn rats and chronic intrauterine hypoxia induced by phenytoin caused oxidative stress followed by organ ischaemia/reperfusion and reactive oxygen species generation. In biochemical quantification of oxidative stress we used the activity of the lysosomal enzyme N-acetyl-B-D-glucosaminidase (NAGA) and the level of glutathione (GSH) in foetal liver and brain, and in the placenta and brain, lungs and liver of newborn rats as markers...
PROTECTIVE EFFECT OF STOBADINE AGAINST ISOPROTERE-NOL INDUCED OXIDATIVE STRESS IN RATS
Tatiana Mačičková, Jana Navarová
MMSL 2001, 70(S2):75-78
This study was carried out to evaluate whether the pyridoindole stobadine (STO), which is an effective cardioprotective drug and a potent antioxidant, had any specific role in changes Of lysosomal enzyme (LE) activity in the rat heart during oxidative stress induced by a high dose of a synthetic catecholamine, isoproterenol (IPN). Oxidative stress induced by catecholamines is a well recognized toxic event. This effect has been extensively observed in the heart, where high levels of catecholamines cause lipid peroxidation, energy depletion and myocardial necrosis accompanied with leakage of lysosomal content and subsequent LE activity changes in most...
STRUCTURAL AND FUNCTIONAL CHANGES IN RAT OFFSPRING INDUCED BY PRENATAL PHENYTOIN ADMINISTRATION
Mojmír Mach, Eduard Ujházy, Michal Dubovický, Jana Navarová, Pavel Blažíček, Ladislav Šoltés
MMSL 2001, 70(S2):79-82
Phenytoin (sodium salt), a developmental neurotoxicant, was administered orally by gavage (150 mg/kg) to pregnant rats on days 7—18 of gestation. Various developmental and behavioural indices were evaluated. This study suggest that prenatal phenytoin exposure may result in developmental, behavioural deficits and neurochemical changes.
INTERACTION OF L-CARNITINE AND 3H-7-METHOXYTACRINE FROM THE ASPECT OF THE BIODISTRIBUTION AND EFFECT ON THE BRAIN ACETYLCHOLINESTERASE ACTIVITY
Zbyněk Svoboda, Josef Herink, Josef Bajgar, Jaroslav Květina, Bohuslav Černý
MMSL 2001, 70(S2):83-86
7-methoxytacrine (MEOTA) is a reversible inhibitor of acetylcholinesterase and it belongs to a group of drugs, which are known as activators of cognitive functions and could be useful in the therapy of some neurodegenerative disorders such as Alzheimer’s disease. The lower toxicity is its advantage in comparison with tacrine. L-carnitine (CRT) was used to increase penetration of MEOTA through the blood brain barrier in rat. 3H-MEOTA was administered intravenously (5 mg/kg), orally (5 and 0.5 mg/kg) or intramuscularly (100 mg/kg) to rats in order to evaluate its pharmacokinetic properties. The intramuscular administration was chosen...
EFFECT OF ACETYL-L-CARNITINE ON THE ANTICHOLINESTERASE ACTIVITY OF 7-METHOXYTACRINE IN VIVO
Josef Herink, Jiří Bajgar, Zbyněk Svoboda, Jaroslav Květina, Pavel Živný, Vladimír Palička
MMSL 2001, 70(S2):87-89
The aim of this work is a comparison of repeated peroral (p.o.) administration, i.e., three consecutive doses separated by 24-hour intervals of acetyl-L-carnitine (ALC) and L-carnitine (CRT) on the antiacetylcholinesterase potency of 7-methoxytacrine (MEOTA) given intramuscularly (i.m.) in a dose of 100 mg/kg. Changes of acetylcholinesterase activity were determined in the frontal cortex, hippocampus, medial septum, and basal ganglia in rats.Repeated administration of CRT in doses of 100, 250, 300 and 400 mg/kg augmented the anticholinesterase activity of MEOTA in the frontal cortex and septum, higher doses of 250, 300 and 400 mg/kg also increased...
THE COMPARISON OF EFFECT OF BILE ACIDS ON THE HEART OF NORMAL RATS AND RATS WITH ISOPRENALINE INDUCED CARDIOMYOPATHY
D. Chaloupková, V. Štětinová, J. Květina
MMSL 2001, 70(S2):90
The aim of the work was the comparison of effects of bile acids, mostly used in the therapy, on some parameters of heart activity after their chronical administration. Their possible effects on cardiovascular system are partially known from literature (1,2). Chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA) were administered orally once a day in doses 1 g/kg and 0.5 g/kg respectively during 4 weeks. Female rats intoxicated with a dose of isoprenaline 30 mg/kg administered subcutaneously 24 hours before the experiment were used. ECG and blood pressure were measured using Mingograf Siemens-Elema at the beginning and...
ATTEMPT OF DRUG TARGETING USING MODEL CYTOSTATIC AGENT AND EXCIPIENT (EXPERIMENTAL RABBITS)
Jiří Pastera, Jaroslav Květina, Zbyněk Svoboda, Jaroslav Vižďa, František Trejtnar, Milan Dittrich, Leo Konrád
MMSL 2001, 70(S2):91-95
Selective biodistribution (targeted to liver only, without adverse reactions in other organs) of a model cytostatic agent, 131I-radiolabelled docetaxel, was studied with lipiodol (20% emulsion of lipophilic x-ray contrast, ethiodized poppy seed oil) as an excipient. 131I-lipiodol alone was compared with a mixture of 131I-alocetaxel + non-radiolabelled lipiodol. Emulsions were administered to rabbits in ketamine-xylasine anaesthesia by slow infusion either to v. portae (after laparotomy) or to v. jugularis. Time-dependence of biodistribution was qualitatively estimated by 12-min whole body scintigraphy with gammacamera,...
EFFECT OF DEFERIPRONE ON LEAD-INDUCED OXIDATIVE DAMAGE AND TRACE ELEMENT LEVEL IN RATS
Dana Kotyzová, Vladislav Eybl, Jaroslav Koutenský, Věra Míčková
MMSL 2001, 70(S2):96-100
Lead (Pb) exerts prooxidative effects and causes oxidative damage to various tissues by altering their antioxidant system. In the experiments male CD rats (Charles River) were treated twice a week with lead acetate at the dose of 12.5 mg/kg body weight ip for 4 weeks with and without Sc co-administration of deferiprone [Lipomed, Switzerland] (LI) at the dose molar ratio to lead acetate 10:1. Pb induced the lipid peroxidation (LPO) in both, the liver and the brain. LI prevented this effect of lead in the liver but not in the brain. L] alone did not change the LPO in liver whereas in the brain an elevation of LPO occured. The level of reduced glutathione...
AN APPRAISAL OF SINGLE ORGANS AND TISSUES LOADING AFTER XENOBIOTIC INVASION IN ORGANISM BY MEANS OF EXTRACTIONS POTENCIES CALCULATED USING FIRST PASS EFFECT (MODEL METHOTREXATE) IN RATS
V. Grossmann, J. Stuchlík, L. Šišpera, J. Martínková
MMSL 2001, 70(S2):101
In the study of effect of New Chemical Entity (NCE) entering in organism it is advantageous to know the concentration of its loading the single organs and tissues. The greater stress is, the higher probability of undesirable effect and higher influence of pathologically changed organ function on effect kinetics and dosing can originate. The indicator of the stress degree can be the extraction potency (EP) of organ and tissues calculated using AUCS of plasma levels after administration of NCE in part of blood circuit before and after supplying the studied organ or area (2). Subtracting relation between these AUCS from one it is possible obtain...
INDIVIDUAL SUSCEPTIBILITY TO TOXIC COMPOUNDS: ROLE OF CYTOCHROMES P450
Pavel Anzenbacher, Roman Zuber, Josef Fusek
MMSL 2001, 70(S2):102-103
The response of an organism to xenobiotic, often toxic, compounds is determined by various factors. One of the most important ones is the presence of enzymes metabolizing the xenobiotics; among them, the most prominent enzymes are cytochromes P450 (abbrev. CYP). The CYP enzymes metabolizing xenobiotics are present in the liver as well as in other parts of the gastrointestinal tract, in the lung, kidney, heart, nasal epithelium, leukocytes and other tissues. Their localization is expected to be connected with their yet unknown physiological function(s).