Study of toxicity and peculiarities of biological effects of nanocomposite pectin-Ag: results of a subchronic experiment

2021 ◽  
Vol 29 (5) ◽  
pp. 25-33
Author(s):  
Vadzim Michailovich Vasilkevich ◽  
Ruslan Valerievich Bogdanov ◽  
Ksenia Sergeevna Gilevskaya ◽  
Victoria Igorevna Kulikouskaya
Keyword(s):  
Biological Effects ◽  
Experimental Studies ◽  
Laboratory Animals ◽  
Intragastric Administration ◽  
Pectin Content ◽  
Target Organs ◽  
Toxicological Studies ◽  
Threshold Doses ◽  
20 Nm ◽  
Dose Dependent

Introduction. Nanocomposites synthesized by the “green chemistry” method do not contain toxic chemicals (reducing agents and organic solvents) as carriers and/or stabilizing shells. One of the representatives of this group of materials are nanocomposites based on silver, which are increasingly used in medical practice, veterinary medicine, and in some other fields. Material and methods. The nanocomposite is Ag0 nanoparticles coated with a highly methoxylated pectin shell. The concentration of Ag0 nanoparticles in the hydrosol of the pectin-Ag nanocomposite is 1.65 mmol/l, and the pectin content is 7.5 mg/ml. The size of the synthesized pectin-Ag nanocomposite is ~20-30 nm, more than 90% of the particles have a diameter of less than 20 nm, the value of the ξ-potential is 45.3 ± 0.7 mV. Toxicological studies were carried out on outbred rats. The main goal of the research was to study the toxic effects of the pectin-Ag nanocomposite in a subchronic experiment (90 days). At the end of the experiment, a complex of behavioral and clinical and laboratory parameters was determined, which made it possible to assess the biological effect of the nanocomposite on animals. The research results were statistically processed. Results. With subchronic intragastric administration of the pectin-Ag nanocomposite to laboratory animals (rats) for 3 months at doses of 50, 500, and 5000 mg/kg, it was found that the nanocomposite exhibits a dose-dependent general toxic effect with critical target organs - the liver and spleen and the main biochemical markers of toxicity effect - aminotransferase, alkaline phosphatase and lactate dehydrogenase. Conclusion. Experimental studies have made it possible to substantiate the threshold doses of the hydrosol of the pectin-Ag nanocomposite for the intragastric route of intake.

Actual issues of hygienic regulation and creation of safe working conditions at pharmaceutical manufacturing enterprises

2020 ◽  
Vol 60 (10) ◽  
pp. 640-644
Author(s):  
Vadim M. Vasilkevich ◽  
Ruslan V. Bogdanov ◽  
Elena V. Drozdova
Keyword(s):  
Pharmaceutical Industry ◽  
Working Conditions ◽  
Experimental Studies ◽  
Pharmaceutical Products ◽  
Laboratory Animals ◽  
Production Environment ◽  
Basic Principles ◽  
Toxicological Studies ◽  
Health Disorders ◽  
Safe Working

Introduction. The working conditions of pharmaceutical industry workers are characterized by the combined effect of unfavorable factors of the production environment, among which the leading one is chemical. The aim of study is to substantiate the basic principles and criteria for hygienic regulation of pharmaceutical products in their production to ensure safe working conditions for employees based on the results of their own research and existing requirements of technical regulations. Materials and methods. Analysis of working conditions and the prevalence of health disorders in pharmaceutical workers (according to literature data), toxicological studies of pharmaceutical substances on laboratory animals, scientific justification of hygiene standards in the air of the working area. Results. Among employees of the pharmaceutical industry, the predominant forms of production-related health disorders are diseases of the respiratory system, as well as skin dermatitis of allergic origin, liver and biliary tract diseases. Based on the results of experimental studies of domestic pharmaceutical products for the treatment of cardiovascular, oncological and mental diseases that have priority socio-economic significance, the basic principles and features of the practice of justifying the hygienic standards of medicines in the air of the working area are developed and systematized. Conclusions. During hygienic rationing of medicines, it is necessary to use a differentiated approach that allows, based on the analysis of information about the chemical structure, physical and chemical characteristics, production conditions, pharmacotherapeutic activity, and the results of studying the toxic effect in an experiment on laboratory animals, to determine the maximum permissible content in the air of the working area of medicines or to justify the prohibition of isolation with reasoned recommendations for their safe production.

scholarly journals To the problems of toxicity testing of nanorized objects (Literature review)

2021 ◽  
Vol 90 (1) ◽  
pp. 75-80
Author(s):  
OB Leonenko
Keyword(s):  
Biological Effects ◽  
Chorioallantoic Membrane ◽  
Toxicity Testing ◽  
Aquatic Organisms ◽  
Alternative Methods ◽  
Laboratory Animals ◽  
Scientific Publications ◽  
Toxicological Studies ◽  
Analytical Review

Aim of the Research. To present and summarize data on the problems of assessing the toxicity and hazards of nanosized particles due to the peculiarities of their activity and variability, which prove the need to develop a vector of research in vitro. Materials and Methods. Targeted testing can provide broad coverage of nanoproducts, reduce the cost and time of research, as well as the number of animals used in experiments. Various model test systems are proposed for use, the use of which is possible to detect harmful effects of man-made nanomaterials, and also for other chemicals: cellular and subcellular elements (mitochondria, microsomes, DNA, chorioallantoic membrane vessels), organs of laboratory animals, the simplest (unicellular) organisms, microorganisms, various aquatic organisms, plants, insects, sperm of cattle. Biotesting is one of the methods of research in the field of toxicology, used to determine the degree of toxic effects of chemical, physical and biologically unfavorable factors that are potentially dangerous to humans and components of ecosystems. An analytical review of scientific publications was carried out using the abstract databases of scientific libraries Pub Med, Medline and text databases of scientific publishing houses Elsevier, Pub Med, Central, BMJ group as well as other VIP databases. Results and Conclusions. Recently, publications emphasize that the manifestations of biological effects depend on changes in the characteristics and properties of nanomaterials. These facts cannot be taken into account in standard toxicological studies. One of the ways to intensify tests and reduce their cost may be the use of accelerated toxicological studies on simple biological systems (models). In this regard, the development and implementation of alternative methods in vitro has become one of the leading areas of toxicological research of nanomaterials. Key Words: nanoparticles, toxicity, testing.

scholarly journals Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food

2021 ◽  
Vol 18 (7) ◽  
pp. 3332
Author(s):  
Olga V. Naidenko ◽  
David Q. Andrews ◽  
Alexis M. Temkin ◽  
Tasha Stoiber ◽  
Uloma Igara Uche ◽  
...  
Keyword(s):  
Immune System ◽  
High Throughput ◽  
Environmental Protection Agency ◽  
High Throughput Screening ◽  
Molecular Mechanisms ◽  
Specific Activity ◽  
Laboratory Animals ◽  
In Vitro Assays ◽  
Toxicological Studies

The development of high-throughput screening methodologies may decrease the need for laboratory animals for toxicity testing. Here, we investigate the potential of assessing immunotoxicity with high-throughput screening data from the U.S. Environmental Protection Agency ToxCast program. As case studies, we analyzed the most common chemicals added to food as well as per- and polyfluoroalkyl substances (PFAS) shown to migrate to food from packaging materials or processing equipment. The antioxidant preservative tert-butylhydroquinone (TBHQ) showed activity both in ToxCast assays and in classical immunological assays, suggesting that it may affect the immune response in people. From the PFAS group, we identified eight substances that can migrate from food contact materials and have ToxCast data. In epidemiological and toxicological studies, PFAS suppress the immune system and decrease the response to vaccination. However, most PFAS show weak or no activity in immune-related ToxCast assays. This lack of concordance between toxicological and high-throughput data for common PFAS indicates the current limitations of in vitro screening for analyzing immunotoxicity. High-throughput in vitro assays show promise for providing mechanistic data relevant for immune risk assessment. In contrast, the lack of immune-specific activity in the existing high-throughput assays cannot validate the safety of a chemical for the immune system.

Ligand-Regulated Expression of TNF Receptors 1 and 2 Determines Receptor-Mediated Functional Responses

2021 ◽  
pp. 1-12
Author(s):  
Alina Alshevskaya ◽  
Olga Koneva ◽  
Irina Belomestnova ◽  
Julia Lopatnikova ◽  
Irina Evsegneeva ◽  
...  
Keyword(s):  
Biological Effects ◽  
High Expression ◽  
Functional Responses ◽  
Double Positive ◽  
Dependent Effect ◽  
Similar Expression Profile ◽  
Proliferation Response ◽  
Dose Dependent ◽  
Dose Dependent Effect ◽  
Mcf 7

<b><i>Introduction:</i></b> Modulating specific biological effects through the changes in cytokine receptors’ expression level remains poorly understood. This study aimed to investigate the influence of the dose-dependent effect of TNF on the balance between proapoptotic and proliferation response depending on the parameters of TNFR1/2 expression density. <b><i>Methods:</i></b> Tumor cell lines (HEp-2, K-562, MCF-7, ZR-75/1, MOLT-4, IM-9, and Raji) were characterized for TNFR1/2 co-expression using flow cytometry and were studied to reveal the dose-dependent effect of rhTNF on cell cycle and apoptosis parameters. The associations among the studied parameters were estimated by correlation and regression analysis. <b><i>Results:</i></b> It was found for ZR-75/1 cells (the cell line characterized by high expression of both types) that a dose-dependent increase in expression of both types of TNF-α receptors on cells reduces the proliferative activity of cells. For MOLT-4 cells (which are characterized by lower expression), an increase in proliferative response of cells was positively associated with the percentage of both TNFR1<sup>+</sup> and TNFR2<sup>+</sup> cells. However, opposite effects on the cells were shown for the K-562 and MCF-7 lines having a similar expression profile. A similarity (a large percentage of double-positive cells) was revealed for the lines having similar effects (K-562 and ZR-75/1). <b><i>Conclusions:</i></b> High expression of TNF receptor type 1 is not always associated with predominant activation of proapoptotic pathways. However, in the case of simultaneous high expression of both types of receptors, the proportion of double-positive cells is crucial for the activation of either the proapoptotic or proliferation pathways.

Protein kinase C isotypes in human erythroleukemia cell proliferation and differentiation

1992 ◽  
Vol 101 (3) ◽  
pp. 671-679
Author(s):  
B.A. Hocevar ◽  
D.M. Morrow ◽  
M.L. Tykocinski ◽  
A.P. Fields
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cellular Proliferation ◽  
Biological Effects ◽  
Growth Arrest ◽  
Tumor Promoter ◽  
Induced Differentiation ◽  
Megakaryocytic Differentiation ◽  
Kinase C ◽  
Dose Dependent

The human erythroleukemia (K562) cell line is induced to differentiate into megakaryocytic cells by treatment with the tumor promoter phorbol myristate acetate (PMA). PMA-induced differentiation is characterized by (1) almost complete cessation of cellular proliferation, (2) expression of the megakaryocytic cell surface marker glycoprotein IIb/IIIa (gpIIIa), (3) increased secretion of granulocyte/macrophage-colony stimulating factor (GM-CSF) and (4) increased secretion of interleukin-6 (IL-6). PMA-induced differentiation is dose-dependent with maximal activity seen at 10 nM PMA. In contrast, bryostatin (bryo), a structurally distinct protein kinase C (PKC) activator, fails to induce megakaryocytic differentiation or growth arrest at the concentrations tested (0.01-100 nM). Rather, bryo inhibits PMA-induced growth arrest and megakaryocytic differentiation in a dose-dependent fashion (full inhibition at 100 nM). The divergent biological effects of PMA and bryo correspond to the differential activation and translocation of PKC isotypes in K562 cells. PKC isotype analysis demonstrates that undifferentiated cells express both alpha and beta II PKC but no detectable beta I, gamma or epsilon PKC. Treatment of cells with either PMA or bryo leads to rapid translocation of both alpha and beta II PKC from the cytosol to the non-nuclear particulate fraction. However, bryo also induces selective translocation of beta II PKC to the nuclear membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

The current state of mycotoxin biomarker development in humans and animals and the potential for application to plant systems

2011 ◽  
Vol 4 (3) ◽  
pp. 257-270 ◽  
Author(s):  
T. Baldwin ◽  
R. Riley ◽  
N. Zitomer ◽  
K. Voss ◽  
R. Coulombe Jr. ◽  
...  
Keyword(s):  
Disease Risk ◽  
Biological Effects ◽  
Fusarium Verticillioides ◽  
Laboratory Animals ◽  
Plant Tissues ◽  
Living Plant ◽  
Disease Symptoms ◽  
Mechanisms Of Toxicity ◽  
Livestock Feeds ◽  
Commercially Important

Filamentous fungi that contaminate livestock feeds and human food supply often produce toxigenic secondary metabolites known as mycotoxins. Among the hundreds of known mycotoxins, aflatoxins, deoxynivalenol, fumonisins, ochratoxin A and zearalenone are considered the most commercially important. Intense research on these mycotoxins, especially aflatoxin, has resulted in the development of 'biomarkers' used to link exposure to disease risk. In the case of aflatoxin this effort has led to the discovery of both exposure and mechanism-based biomarkers, which have proven essential for understanding aflatoxin's potential for causing disease in humans, including subtle effects on growth and immune response. Fumonisin biomarkers have also been used extensively in farm and laboratory animals to study the fumonisin-induced disruption of cellular and systemic physiology which leads to disease. This review summarises the status of mycotoxin biomarker development in humans and animals for the commercially important mycotoxins. Since the fungi responsible for the production of these mycotoxins are often endophytes that infect and colonise living plant tissues, accumulation of mycotoxins in the plant tissues may at times be associated with development of plant disease symptoms. The presence of mycotoxins, even in the absence of disease symptoms, may still have subtle biological effects on the physiology of plants. This review examines the question of whether or not the knowledge gained from mechanistic studies and development of biomarkers in animal and human systems is transferable to the study of mycotoxin effects on plant systems. Thus far, fumonisin has proven amenable to development of mechanism-based biomarkers to study maize seedling disease caused by the fumonisin producer, Fusarium verticillioides. Expanding our knowledge of mechanisms of toxicity and the overt and subtle effects on animal, human, and plant systems through the identification and validation of biomarkers will further our ability to monitor and limit the damage and economic impact of mycotoxins.

scholarly journals The acylation of proteins by xenobiotic amphipathic carboxylic acids in cultured rat hepatocytes

1988 ◽  
Vol 254 (1) ◽  
pp. 39-44 ◽  
Author(s):  
R Hertz ◽  
J Bar−Tana
Keyword(s):  
Protein Synthesis ◽  
Carboxylic Acids ◽  
Mode Of Action ◽  
Biological Effects ◽  
Rat Hepatocytes ◽  
Protein Adducts ◽  
Cultured Rat Hepatocytes ◽  
Acylated Proteins ◽  
Dose Dependent ◽  
Protein Acylation

Three xenobiotic amphipathic carboxylates, namely MEDICA 16, nafenopin and bezafibrate, which differ remarkably in their hydrophobic backbones, were found to acylate membrane and cytosolic liver proteins in cultured rat hepatocytes. The acylation patterns observed were time- and dose-dependent, and the acylated residue consisted of the original xenobiotic. The acylation patterns generated by the three xenobiotic carboxylates included common proteins which were acylated by the three xenobiotics (e.g. proteins of 32, 52, 56 and 72 kDa) as well as unique proteins which were specifically acylated by the respective xenobiotics. The acylation of liver proteins by either MEDICA 16 or nafenopin remained unaffected under conditions where protein synthesis was completely inhibited by cycloheximide. Protein acylation thus offers a common mode of action of xenobiotic amphipathic carboxylates, which may, however, result in diverse xenobiotyl-protein adducts. The xenobiotyl-acylated proteins might be involved in triggering some of the biological effects exerted by xenobiotic amphipathic carboxylates employed as hypolipidaemic effectors, peroxisomal proliferators or preadipocyte convertors.

Possible mediation by luminal somatostatin of bombesin-induced satiety in the cat

1992 ◽  
Vol 263 (1) ◽  
pp. R84-R88
Author(s):  
A. Bado ◽  
L. Moizo ◽  
J. P. Laigneau ◽  
M. Gauthier ◽  
M. Dubrasquet ◽  
...  
Keyword(s):  
Food Intake ◽  
Intragastric Administration ◽  
Gastric Fistula ◽  
Daily Food ◽  
Dependent Inhibition ◽  
Gastric Lumen ◽  
Dose Dependent Inhibition ◽  
Bombesin Receptor ◽  
Dose Dependent ◽  
Somatostatin 14

Intravenous bombesin produced a dose-related stimulation of luminal gastric somatostatin output and a concomitant dose-dependent inhibition of food intake in the gastric fistula cat. Maximal food intake inhibition was observed at 1,280 pmol.kg-1.h-1 and corresponded to 65 +/- 7% (P less than 0.01). These effects of bombesin were dose dependently abolished by the specific bombesin-receptor antagonist, [Leu13-psi(CH2NH)-Leu14]bombesin. Furthermore, intragastric administration of somatostatin-14, at doses corresponding to those found in the gastric lumen in response to intravenously administered bombesin, significantly inhibited the first 30 min of food intake. This administration had however no effect on total (daily) food intake. We therefore suggest that luminal gastric somatostatin could at least account for bombesin-induced short-term satiety.

scholarly journals Preclinical evaluation of the veterinary drug “Amoxidev 15” for its use in surgical and obstetric practice

2021 ◽  
Vol 23 (103) ◽  
pp. 109-115
Author(s):  
L.-M. Kostyshyn ◽  
R. Sachuk ◽  
Ye. Kostyshyn ◽  
O. Katsaraba
Keyword(s):  
Body Weight ◽  
Soft Tissues ◽  
Control Level ◽  
Subcutaneous Administration ◽  
The Body ◽  
Laboratory Animals ◽  
Veterinary Drug ◽  
Intragastric Administration ◽  
Toxicological Evaluation ◽  
White Rats

Suspension for injection “Amoxidev 15” is prescribed to fur-bearing animals (mink, fox), dogs and cats for the treatment of respiratory diseases (tonsillitis, tracheitis, pneumonia, bronchitis, rhinitis, sinusitis, bronchopneumonia), digestive (gastritis, enteritis, enteritis). genitourinary systems (nephritis, urethritis, urocystitis, mastitis, metritis, agalactia), musculoskeletal system (arthritis, osteoarthritis, joint injuries, tendonitis, hoof lesions), skin and soft tissues (eczema, dermatitis) caused by sensitive drug by microorganisms, including colibacillosis, streptococcus, bronchopneumonia, etc. Toxicological evaluation of the veterinary drug “Amoxidev 15” under the conditions of acute and subacute toxicological experiments on a model of white rats. According to the results of an acute toxicological experiment with intragastric administration of the drug “Amoxidev 15” white rats DL50 could not be calculated because the death of laboratory animals was not detected within 14 days after administration. The maximum administered dose (in absolute weight of the drug) was 20000.0 mg/kg body weight, which allows to refer the drug to class VI toxicity of relatively harmless substances (DL50 > 15000 mg/kg body weight), and the degree of safety to class IV – low-hazard substances (DL50 > 5000 mg/kg). According to the results of an acute toxicological experiment with subcutaneous administration of the drug “Amoxidev 15” white rats DL50 could not be calculated because the death of laboratory animals was not detected within 14 days after administration, the maximum dose was 5000.0 mg/kg body weight, therefore, the drug “Amoxidev 15” when administered subcutaneously by toxicity can be classified as class VI substances relatively harmless (DL50 Subcut > 4500.0 mg/kg). When administered subcutaneously to white rats, the drug “Amoxidev 15” under conditions of subacute toxicological experiment in doses of 0.1–1.0 ml/kg does not cause hemo-, hepato- and nephrotoxic effects on the body of laboratory animals, although 3-day administration of the drug in a dose 1.0 ml/kg body weight caused an increase in the activity of hepatospecific enzymes ALT and AST by 12.5 and 11.1 % (P < 0.05), respectively, relative to the control, which was restored to the control level 7 days after cessation.

scholarly journals EVALUATION OF TOXIC EFFECTS OF MAGNETIC CONTRAST DIAGNOSTIC GADOLINIUM-CONTAINING NANOCOMPOSITE

2019 ◽  
Vol 98 (10) ◽  
pp. 1161-1165
Author(s):  
Larisa M. Sosedova ◽  
E. A. Titov ◽  
M. A. Novikov ◽  
V. A. Vokina ◽  
V. S. Rukavishnikov
Keyword(s):  
Nervous Tissue ◽  
Chemical Elements ◽  
Biological Effects ◽  
Experimental Studies ◽  
Biological Response ◽  
Immunohistochemical Method ◽  
Ether Anesthesia ◽  
Compensatory Response ◽  
White Rats ◽  
Liver And Kidney

Introduction. In recent years, magnetic nanoparticles, which can simultaneously have a therapeutic effect on the pathological focus, are used to magnify contrast enhancement and increase diagnostic sensitivity during magnetic resonance therapy (MRT). The last is carried out by the effective capture of neutrons, which among all the chemical elements is most pronounced in gadolinium. The use of gadolinium nanoparticles encapsulated in a polymeric matrix allows increasing the bioavailability of nanoparticles, reduces the possible toxicity of drugs. Aim. Evaluation of impact of new nanocomposite magnetically active metal complex gadolinium system on the morphofunctional state of the nervous tissue, liver, and kidney of rats. Material and methods. Experimental studies of biological effects of gadolinium-arabinogalactan nanocomposite (Gd-AG) were carried out on rats that were injected intraperitoneally for 10 days at the dose of 500 μg/kg in 0.5 ml of saline. Animals were sacrificed by decapitation under light ether anesthesia the next day after the end of exposure. To perform pathological studies, frontal sections of the temporal-parietal zone of the sensorimotor cortex, liver and kidney tissues were stained on ordinary histological glass slides with hematoxylin and eosin for viewing microscopic picture. The immunohistochemical method was used to determine the activity of the bcl-2, caspase-3 and hsp70 modulatory protein in apoptosis of white rats in brain neurons and to study the biological response of the organism at the subcellular level. Results. Histological analysis of tissues revealed a pronounced compensatory response of liver, a violation of the functional activity of kidneys. A decrease in the total number of normal neurons per unit area in brain tissue and an increase in the number of acts of neuronophagy indicate the initial stage of neurodegenerative process. Evaluation of the intracellular metabolism of neurons has not established the presence of signs characteristic of apoptotic process. Conclusion. The subacute effect of Gd-AG in a dose of 500 µg/kg causes a disturbance of morphofunctional state of liver, kidneys and nervous tissue, as well as modulation of cellular proteomics.

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