The Journal “Toksikologicheskiy vestnik” (Toxicological Review)
A simultaneous analysis of scientific resources and regulatory and legal documents over 1970–2012 concerning a complex application of artificial detoxification methods (ADM) (operation of blood replacement and sorptiondialysis detoxification) at acute poisoning (AP) showed a close temporal relationship between the introduction of ADM in toxicological department of N.V.Sklifosovsky Research Institute of Emergency Medicine and other toxicological centers (departments) of Russia and appearing of legal documents requiring their application in accordance with guidelines based on clinical and laboratory data. Activities of the Toxicology Department at the N.V. Sklifosovsky Institute, unparalleled in scope and range, give reason to consider it is a leading scientific and methodological base for the development of normative and legal documents regulating the use of ADM as part of Toxicology Service of Russia. It is noted that delays in the implementation of a comprehensive detoxification in pathology under consideration at the regulatory and legal level entail the impossibility of providing the most effective specialized medical care.
Keywords: acute poisoning, treatment, artificial detoxification, regulatory and legal frame
A comparative assessment of new peptide drugs with a common molecular structure Acetyl–Lys– Lys–Arg–Arg–amide (index KK) and molixan as correction means for CNS functional disorders evolving in toxicogenic and somatogenic stages in ethanol-intoxicated rats is presented. 40% ethanol was delivered intragastrically in a dose of 1 LD50 (8 g/kg). Peptides KK1 and KK10 were administrated intranasally in a dose of 40 mkg/kg, molixan has been injected intraabdominally in a single dose of 30 mg/kg, 30 min. after the intoxication onset. It was found out that 1 LD50 dose of ethanol delivered to rats at the intoxication toxicogenic stage disturbs the neurological status and also leads to their 44% death and delivered at the somatogenic stage, ethanol causes impairments in survived rats memory, ability to training and physical activity over two weeks after intoxication onset. When acute alcohol intoxication was corrected with peptide preparations KK1 and KK10 , the rats survival was 100% and 88% when molixan was used. Along with it, the therapeutic introduction of KK1 and KK10 peptides allowed to avoid the emergency of states classified as “coma’” and posed anti-amnesic effect. The use of KK line peptides and molixan accelerates restoration rates of learning ability, physical endurance and motor coordination in poisoned animals by 1.5-2 times.
Keywords: ethanol, poisoning, treatment, peptides, survival, central nervous system function
Toxicity of AdeLact™, a novel medicinal product on the basis of recombinant pseudo-adenoviral particles expressing human lactoferrin gene, was studied. Acute toxicity was evaluated in mice and rats, and sub-chronic toxicity was evaluated in rats and rabbits. According to its acute toxicity, AdeLact™ was classified as a low hazardous preparation and according to its sub-chronic toxicity, as a moderate hazardous preparation. In toxic doses, AdeLact™demonstrated moderate hepatic and renotropic toxicity. Inflammatory processes might develop in lungs after administration of AdeLact™. Intravenous infusion of AdeLact™ produces a mild and fully recoverable local effect.
Keywords: AdeLact™, human lactoferrin gene, human lactoferrin, adenovirus of serotype 5, general toxicity, acute toxicity, sub-chronic» toxicity
Allergenicity and immunotoxicity of Stodal preparation was assessed. Immunization of guinea pigs with Stodal in doses of 1 ml/kg and 10 ml/kg according to a standard scheme or mixed with complete Freund’s adjuvant did not provoke a systemic anaphylactic reaction or delayed allergenic reactions in animals. A single per os administration of the Stodal preparation in doses of 1mg/kg and 10 ml/kg to CBA line mice did not affect the inflammation response to concanavalin A (Con.A). In F1 (CBA x C57BL/6) mice , Stodal perorally administrated at a dose of 1 ml/mg over 14 days caused a significant increase of thymus mass index and cellularity by 41.5% and in a dose of 10 ml/kg the thymus mass increased by 28.7% . The preparation administrated in the doses of 1 ml/kg and 10 ml/kg did not affect peritoneal macrophage phagocytic activity and indicators of the neutrophils hemi-luminescent response to opsonized zymosan. A two week administration of Stodal preparation in doses of 1 ml/kg and 10 ml/kg to CBA and C57BL/6 strain mice induced a significant stimulation of the humoral immune response. In F1 (CBA x C57BL/6) hybrid mice , 1 ml/kg dose administration induced an authentic increase of cellular immunity indicators. Thus, the Stodal preparation in the dose range investigated does not produce allergenic responses of non-delayed and delayed types and pseudoallergic reactions, stimulates humoral and cellular immunity and does not produce immune-toxic effect.
Keywords: Stodal preparation, systemic anaphylactic reaction, delayed hypersensitivity, inflammation response to concanavalin A, phagocythosis, hemiluminescence, humoral immune response, cellular immune response, immunotoxicity
A combination of taurine (20g/mole, 2.5 g) with zinc diaspartate (1 g/mole, 0.35g) named “taucine”, administrated in the rat stomach at doses of 250 mg\kg and 500 mg/kg over 14 days has a dose-dependent nephro-protective action in rats with sublimate nephropathy ( intraabdominally 0.1 mg/kg over 14 days) . It manifests in an increased volume of the primary urine in cortical nephrons glomerales because of a weakened compression of their capsule by hydropic fluid, in reduction of the inner diameter of cortical nephrons proximal convoluted tubules as consequence of a less pronounced «inner tubular» hydronephrosis and increased height of lining epithelial cells. A detailed analysis of the latter shows that they are less damaged by sublimate: the percentage of undamaged cells increases because of decrease with destruction of apical sections and increase of cells height by as well.
Keywords: rats, sublimate nephropathy, combination of taurine with zinc diaspartate, nephro-protective action
Investigations were carried out into mutagenic and mitosis modifying action (Allium test) of imidazole new polycyclic condensed derivatives having a high ability to embed into DNA molecules: 7-trifluor methyl pyrido [1,2- a] benzimidazole, 7- nitropyrido[1,2-a] benzimidazole, 7- amino pyrido [1,2- a] benzimidazole, 8-nitro- 7-trifluor methyl pyrido[1,2-a]benzimidazole, 8-amino- 7-trifluor methyl pyrido[1,2-a] benzimidazole. The evaluation of cytotoxic effect of compounds under investigation was performed by comparing with toxicological characteristics of a widely used DNA –intercalator 9-amino acridine. All azagetero cycles induced reduction of the prophase index evidencing their impact on the process of DNA replication. The most wide spread mutations were “bridge” type pathologies as a result of reunion of different daughter cells chromosomes and obliteration and losses of entire chromosomes at cells division. All mono- and di-substituted pirido[1,2-a] benzimidazoles produced a lesser mitodepressive and mutagenic action than 9-amino acridine. Monosubstituted pirido[1,2-a]benzimidazoles had lesser cytotoxicity and mutagenicity in the A cepa test-system.
Keywords: cytotoxicity, mutagenicity, mito modifying effect, the Allium test, pirido[1, 2-a] benzimidazoles, DNAintercalators
The impact of Potassium Bichromate ( at 1 MAC dose) on morphological and immunological parameters of Wistar rats lymphoid organs was investigated in a chronic experiment (135 days). A lasting uptake of chromium by the Wistar rat organism induces a decrease of thymus mass and thymocytes number, causes a complex of structural and functional alterations evidencing about the status of accidental involution, lymphoreticular hyperplasia and plasmocytic and macrophage transformation of lymphoid nodes and spleen, induces a programmed death of thymocytes and lymphocytes in splenic T-zones and lymphoid nodes. Chromium induces morpho-functional changes in spleen shown by decrease in its weight and number of spelnocytes, lymphoid series cells and on the contrary by increase of erythroid series cells. The impact of chromium on the bone marrow was evident in a decreased level of myeloid series, neutrophils and on the contrary in increased amount of lymphoid cells and the content of erythroid cells as well.
Keywords: Chromium, lymphoid organs, rats .
Toxicity of the preparation BARAKOR 100 was assessed for standard test-objects: phytoplanctonic organisms Phaeodactylum tricornutum Bohin; zooplanctonic organisms Artemia salina and fishes, one-day old fishes – Poecillia reticulate Peters. Toxicity assessment to hydrobionts was based on indicators of mean lethal concentrations LC50 characterizing changes in survival (death) by50% for a determined duration- 24,48 and 96 h (LC50 -24;48;96 h). Based on the toxicity assessment of the preparation, it was established that the preparation BARAKOR 100 refers to very low toxic substances.
Keywords: preparation, phytoplankton, zooplankton, fish, toxicity