Non-toxic Substances Research Articles

Acute toxicity study of a new dibenzofuran oxime derivative GIZH-272 in mice

Relevance. Acute toxicity testing is a common procedure for preclinical safety testing of potential agents. The purpose of this study was to study the acute toxicity of the compound GIZH-272, a new dibenzofuran oxime derivative with anti-ischemic and anticonvulsant effects. Methods. The compound was administered to mice intraperitoneally and orally once. Within 14 days, the condition of the animals was monitored, clinical manifestations of intoxication were recorded, and changes in the dynamics of body weight and its growth were recorded. Results. It was found that the test compound at maximum doses did not lead to the death of mice. Therefore, the data obtained according to the classification of Sidorov K.K. (1973), make it possible to attribute GIZH-272 to the 5th class of toxicity — "practically non-toxic substance". In accordance with GOST 12.1.007-76, the GIZH-272 compound belongs to the 4th hazard class (low-hazard substance) for oral administration.

A Modified Murine Embryonic Stem Cell Test for Evaluating the Teratogenic Effects of Drugs.

Animal-based test systems have traditionally been used to screen for the potential teratogenic activity of drugs. Still, their deficits in predicting precise human-specific outcomes and ethical concerns have led to a need for alternative approaches. In vitro, teratogenicity testing using cell cultures or other in vitro systems is a potential alternative. Of the different in vitro platforms, the mouse embryonic stem cell test (mEST) is currently the most widely used and validated in vitro test for assessing the potential effects of teratogens on early embryonic development. The mEST involves exposing mouse embryonic stem cells to the test compound and monitoring their differentiation for several days.Nevertheless, its predictive ability was comparatively lower when distinguishing weak developmental toxicants from non-toxic substances. Since then, several modifications and adaptations of the mEST protocol have been developed. This chapter describes an alternative method based on molecular approaches to predict embryotoxicity. This method, originated from the mEST, analyzes the expression of differentiation genes involved in the development of mesoderm, endoderm, and stoderm and allows screening embryo-toxicants with different mechanisms of action. The hanging drops embryoid bodies used in the original mEST protocol have been replaced with monolayer culture, and thus the process has been shortened. In general, the method shows higher predictability compared with the traditional ones.

Implementation of a New Solution for the Preservation of Anatomical Specimens Made of Non-Toxic Substances

Implementation of a New Solution for the Preservation of Anatomical Specimens Made of Non-Toxic Substances

Design, Synthesis and Biological Activity of the 4-Thioquinoline Derivative

One of the promising areas in the creation of bioregulators is the modeling of compounds that combine several pharmacophores. The design of new highly efficient and low-toxic cytoprotectors is largely based on the derivatives of nitrogen-containing heterocycles, and quinoline plays a significant role among these compounds. The researchers evaluated the toxicity of the tested compounds in silico, in vitro, and in vivo, which allowed determiningseveral factors that affect the level of toxic action of 4-thioquinoline derivatives and the direction of non-toxic substances in this sequence. The studied 4-thioquinolines showed a moderate antiradical action in the experiment, inferior to the reference antioxidant Acetylcysteine. The most active compounds are 7-chloro-4-thioquinoline derivatives with propanoic acid residues in the 4th position. 2-(7-chloroquinolin-4-ylthio)propanoic acid and sodium salt of 2-amino-3-((7-chloroquinolin-4-yl)thio)propanoic acid showed the most promising results and their antioxidant action was higher than Tiotriazolin (the comparator) by 27 % and 41 %, respectively. The studied compounds showed a protective effect under H2O2-induced oxidative stress against male sperm according to the main indicators of sperm fertility. It was found that the compounds withresidues of succinic acid, cysteamine, or cysteine in the molecule structure are not inferior to reference drugs. On average, 2-((7-chloroquinolin-4-yl)thio)succinic acid and 2-((quinolin-4-yl)thio)ethanaminedihydrochloride exceeded the comparison drug Acetylcysteine and were on a par with the effect of Ascorbic acid.

Exploring the utilization of polylactic acid-based materials in medicine: Contemporary innovations and trends

A biocompatible, non-toxic substance is polylactic acid (PLA), which is also biodegradable. This material has been studied for decades and has been commercially used in some fields. The potential of defined PLA for different medical applications, including drug delivery systems, wound healing, bone implants, and vascular grafts, was described in this paper. Various methods of characterization and modification of PLA have been investigated to optimize its properties for specific applications. Typically, additional polymers are introduced into PLA to enhance its functional properties. The key feature of PLA is its capacity for degradation in the human body without introducing harmful byproducts. Adjustments to PLA composition can control degradation rates, influencing drug delivery or the persistence of implants. By applying a cold plasma treatment in order to alter the PLA-based polymer's surface, the capacity of the material to transport drugs may be changed. The change of parameters in coaxial electrospinning can produce different PLA-based products for different use. However, certain challenges remain, such as improving the adhesion of PLA and production of low-price PLA.

Synergy of rapid adsorption and photo-Fenton-like degradation in CoFe-MOF/TiO2/PVDF composite membrane for efficient removal of antibiotics from water

The reasonable construction of composite membranes with dual functions of rapid adsorption and photo-Fenton-like oxidation degradation holds great significance in the field of wastewater purification. Herein, a poly(vinylidene fluoride)-based composite membrane (denoted as CFT/PVDF) was meticulously prepared through a nonsolvent induced phase separation (NIPS) process with the introduction of cobalt-iron metal–organic framework (CoFe-MOF) and TiO2 (Degussa P25). The composite membrane exhibited an excellent adsorption ability for removing a variety of organic pollutants from water. With the integration of adsorptive filtration and in situ photo-Fenton-like degradation, the removal efficiency of tetracycline hydrochloride reached up to 92.9% through the CFT/PVDF membrane in one filtration process, and the remarkable performance could be maintained after ten consecutive cycles. Moreover, a group of CFT/PVDF membranes was connected in series to realize the fast and continuous wastewater treatment. The photo-Fenton-like oxidation mechanism and possible degradation pathways were proposed on the basis of active-species detections and degradation intermediates analysis. The toxicological analysis indicated that tetracycline was in situ degraded into less toxic intermediates and even nontoxic substances by the CFT/PVDF composite membrane. This work provides some valuable guidance on the construction of self-cleaning membranes for sustainable wastewater remediation and potential applications.

Urban open-air chemical sensing using a mobile quantum cascade laser dual-comb spectrometer

Detection of airborne chemical releases in densely populated urban environments requires precise sensors with high temporal and spatial resolution capable of covering large areas. For this purpose, we present a mobile mid-infrared quantum cascade laser dual-comb spectrometer for identification and quantification of chemical plumes. Field tests with the remote sensor were conducted during daytime in the downtown Boston area over a five day period during which chemical releases were simulated by intermittently emitting non-toxic substances. Open-air sensing was performed with retroreflectors positioned at up to 230 m distance and with sensitivities in the ppm m range for one second of averaging time. The field campaign demonstrates a step toward a semiconductor dual-comb spectroscopic sensor in the mid-infrared fingerprint region, suitable for long-term deployments. These types of sensors will be valuable complements to existing optical sensors for urban hazardous gas leak monitoring, air quality assessments, and localization of clandestine chemical production.

STUDIES ON THE TOXICITY OF C-PHYCOCYANIN IN GUPPY FISH AND INFUSORIA PARAMECIUM CAUDATUM

One of the important and urgent tasks, whose successful solution depends on the supply of food to the population, is to increase the production of livestock products. Ensuring a high level of production of livestock products largely depends on the quality of feed, which is determined, first of all, by toxicological control.
 C-phycocyanin is a protein complex that belongs to phycobiliproteins and can be used as one of the potential natural components to improve the feeding of commercial fish.
 In order to establish the safety of the use of active feed components for feeding and ready-made feed into which these components are introduced, first of all, it is necessary to study their effect on the organisms of protozoa and fish, which are used for laboratory research.
 The high sensitivity of ciliates to the appearance of toxic substances in their environment and changes in their concentration led to the use of these organisms for testing the most diverse chemical elements and compounds.
 The article presents the results of studying the effect (harmlessness) of C-phycocyanin on the bodies of protozoa (Paramecium caudatum) and guppy fish.
 When studying the effect of C-phycocyanin on the body of protozoa (Paramecium caudatum), it was established that its use for 48 hours in doses of 5, 10, 25, 50, and 100 mg/l did not cause the death of ciliates. When studying the effect of C-phycocyanin on the body of guppy fish, it was established that its use in doses of 5, 10, 25, 50, and 100 mg/l did not cause the death of fish.
 So, on the basis of the conducted research, it was established that C-phycocyanin belongs to class 4, and is a non-toxic substance for Paramecium caudatum ciliates. In addition, it was established that its use in the above doses did not cause the death of fish, and its LC50 is higher than 100 mg/l.

Basic Substances and Potential Basic Substances: Key Compounds for a Sustainable Management of Seedborne Pathogens

Seedborne pathogens represent a critical issue for successful agricultural production worldwide. Seed treatment with plant protection products constitutes one of the first options useful for reducing seed infection or contamination and preventing disease spread. Basic substances are active, non-toxic substances already approved and sold in the EU for other purposes, e.g., as foodstuff or cosmetics, but they can also have a significant role in plant protection as ecofriendly, safe, and ecological alternatives to synthetic pesticides. Basic substances are regulated in the EU according to criteria presented in Article 23 of Regulation (EC) No 1107/2009. Twenty-four basic substances are currently approved in the EU and some of them such as chitosan, chitosan hydrochloride, vinegar, mustard seed powder, and hydrogen peroxide have been investigated as seed treatment products due to their proven activity against fungal, bacterial, and viral seedborne pathogens. Another basic substance, sodium hypochlorite, is under evaluation and may be approved soon for seed decontamination. Potential basic substances such as essential oils, plant extracts, and ozone were currently found effective as a seed treatment for disease management, although they are not yet approved as basic substances. The aim of this review, run within the Euphresco BasicS project, is to collect the recent information on the applications of basic substances and potential basic substances for seed treatment and describe the latest advanced research to find the best application methods for seed coating and make this large amount of published research results more manageable for consultation and use.

Ultra-small Ni@NiFe2O4/TiO2 magnetic nanocomposites activated peroxymonosulphate for solar light-driven photocatalytic mineralization of Simazine

In the heterogeneous photocatalytic degradation of environmental contaminants the recovery, reuse of employed nanocatalyst was crucial and it is essentially required for the scale up applications. Besides, designing a magnetic material with heterojunction that can effectively oxidize the toxic organic contaminants to non-toxic substance under different reaction conditions including direct solar light irradiation remains a challenge. Considering the above facts, herein, we tailored heterojunction between the magnetic materials and non-magnetic materials with ultra-small Ni nanoparticles modified NiFe2O4/TiO2 nanostructures (Ni@NiFe2O4/TiO2 magnetic nanocomposites) through a simple sonochemical route. The Raman phonons at ∼ 540 cm−1 consistent to nickel metal nanoparticles and the spinel ferrites crystal structure confirmed the formation of Ni@NiFe2O4/TiO2 magnetic nanocomposites. The reduced optical bandgap of the resulting nanocomposites indicated the effective absorption of direct solar light irradiation when compared to the bare TiO2. Thus in-turn, enhanced the photocatalytic efficiency of simazine degradation in the presence of Ni@NiFe2O4/TiO2 magnetic nanocomposites (k´= 11.0 × 10–4 s−1) and augmented the activation of peroxymonosulphate (PMS) in the presence of Ni@NiFe2O4/TiO2 magnetic nanocomposites (k´= 32.5 × 10–4 s−1). Ni@NiFe2O4/TiO2 +PMS exhibited 3 folds enhanced efficiency in the presence of sunlight. The as-prepared NiFe2O4/TiO2 magnetic nanocatalysts were more stable and the efficiency of simazine oxidation was approximately same for the continuous five cycles at the optimized experimental conditions. The Ni@NiFe2O4/TiO2 magnetic nanocomposites preparation and the activation of PMS may promise the applications in an efficient wastewater treatment.

Clinical and pharmacological aspects of vervain (Verbena officinalis L.) using in the treatment of respiratory system diseases (literature review)

In the pharmacotherapy of the respiratory system diseases, phytotherapy attracts attention due to the high preventive and therapeutic potential of biologically active substances of medicinal plants. At the same time, verification of the effectiveness and safety of herbal drugs is necessary. That is why scientific research of folk medicine plants including common verbena (Verbena officinalis L.) of the Verbenaceae family has been carried out.
 The aim of the work is the analysis of verified data on the chemical composition of the herb verbena, the results of pharmacological and toxicological studies directed at determining the effectiveness and safety in the treatment of infectious and inflammatory diseases of the respiratory tract.
 The search for verified data using Internet resources, comparative analysis, systematization and generalization of data were carried out.
 The main secondary metabolites that determine the profile of verbena herb biological activity are iridoid glycosides (verbenalin, aucubine and gastatoside), as well as phenylpropanoid glycosides (verbascoside, isoverbascoside and eukovoside). Thus, the antibacterial and antifungal activity of certain verbena extracts against clinically significant strains of bacteria and fungi has been proven. The anti-inflammatory effect of various extracts of the Verbena herb was established on carrageenan-induced and formalin-induced edema models. The antioxidant effect of certain verbena herb fractions has been proven by in vitro methods. It is important at presence of diseases for which oxidative stress is an important pathogenetic factor. The results of clinical studies have confirmed the anti-inflammatory and antibacterial activity of the vervaine herb decoction applied topically in the case of chronic gingivitis. The expediency of verbascoside use for increasing the barrier functions of the oral mucosa, promoting epithelization, reducing pain and other signs of inflammation in oral mucositis against the background of tumour chemotherapy has been substantiated. Toxicological studies have shown that different verbena herb extracts belong to the class of low-toxic or practically non-toxic substances when taken orally.
 Thus, the antimicrobial, anti-inflammatory and antioxidant effects of verbena, as well as its high level of safety, substantiate the prospects for the use of this medicinal plant in the treatment of the respiratory system diseases.

Preparation of a Magnetic Core-Shell Bioreactor for Oil/Water Separation and Biodegradation.

With the frequent occurrence of offshore oil spills, the effective separation and treatment of oily wastewater are essential to the environment. In this work, the core-shell bioreactor (abbreviated as Fe3O4/MHNTs-CNF@aerogel) was prepared with a core composed of camphor leaf cellulose-based aerogels for loading microorganisms and a shell derived from hydrophobic silane-modified halloysite doping with Fe3O4 for selective absorption of oil and maganetic recycling. The core-shell-structured bioreactor Fe3O4/MHNTs-CNF@aerogel has excellent self-floating properties and can float on water for up to 100 days. The whole core-shell structure not only has excellent oil/water separation performance but also has good microbial degradation performance. By applying it in water containing 5% diesel for the biodegradation test, the biodegradation efficiency of Fe3O4/MHNTs-CNF@aerogel for diesel can reach 82.4% in 10 days. The efficiency was 20% higher than for free microorganisms, and it still had excellent degradation ability after three degradation cycles, with a degradation rate of over 75%. In addition, the result obtained from the study on environmental tolerance shows that Fe3O4/MHNTs-CNF@aerogel possessed a strong tolerance ability under different pH and salinity conditions. The Fe3O4/MHNTs-CNF@aerogel also has superior mechanical properties; i.e., nearly no deformation occurs at 30 kPa. Compared with those conventional oil/water separation materials which can only absorb or separate the oils for water with limited capacity and taking the risk of secondary contamination, our core-shell-structured bioreactor is capable of not only selectively absorbing oil from water through its hydrophobic shell but also degrading it into a nontoxic substance by its microorganism-loaded core, thus showing great potential for practical application in oily wastewater treatment.

Determination of the Toxicity and Sensitizing effect of a Therapeutic Probiotic agent against Intestinal and Concomitant human infections

Studies were conducted on the toxicity and possible sensitizing effect of the lyophilizate of a therapeutic probiotic agent from the most active strains of lactic acid and propionic acid bacteria isolated from healthy people: L. plantarum 2v/A-6+L. brevis B-3/A-26+L. acidophilus 27w/60+P. shermanii 8. Based on the studies conducted to evaluate acute toxicity with an oral single administration of probiotic agent solutions (lyophilizate of lactic acid and propionic acid bacteria) at doses of 300, 2,000, 4,000, and 5,001mg/kg of weight, the toxicity class of the preparation under study has been defined as a non-toxic substance. In the study on laboratory mice of subchronic (subacute) toxicity of probiotic agent (lyophilizate of lactic acid and propionic acid bacteria)) in doses of 5.0×106, 10.0×106, and 15.0×106 CFU, it has been found that the preparation does not have a toxic effect on the body in case of 28-day use. Studies of the chronic toxicity of the probiotic agent (lyophilizate of lactic acid and propionic acid bacteria) in doses of 5.0×106, 10.0×106, and 15.0×106 CFU, in laboratory mice have shown that this preparation does not have a toxic effect on the body in case of prolonged 60-day use and does not cause structural changes in internal organs. It has been established that the therapeutic probiotic agent (lyophilizate of lactic acid and propionic acid bacteria) does not have a potential sensitizing (allergenic) effect on rat peritoneal mast cells.

Physicochemical characterization and biological activity of polysaccharides from the seeds of the turnip brassica rapa

Analysis of the monosaccharide composition showed that the composition of the neutral polysaccharide BSP-1-1 is represented by monosaccharides in the following composition: ribose – 5.05%, arabinose – 56.38%, mannose – 5.87%, glucose – 8.63% and galactose – 24.05%. The composition of the anionic polysaccharide BSP-2-1 is represented by monosaccharides: ribose – 6.35%, arabinose – 60.15%, mannose – 7.19%, glucose – 4.12% and galactose – 22.16%. It was determined that the isolated polysaccharides consist mainly of arabinose (BSP-1-1 – 56.3%, BSP-2-1 – 60%) and galactose (BSP-1-1 – 24%, BSP-2-1 – 22%). Based on the data obtained, it can be assumed that the studied polysaccharides from the seeds of the turnip Brassica rapa belong to the type of arabinogalactans. According to the results of studying the properties of acute toxicity of the BSP polysaccharide from the seeds of the turnip Brassica rapa, it was found that this substance belongs to class V compounds - practically non-toxic substances. With intragastric administration of inulin at doses of 25, 50, and 75 mg/kg and BSP polysaccharide from the seeds of the turnip Brassica rapa at doses of 10, 20 and 30 mg/kg 14 days after the induction of diabetes mellitus, the indicator was close to that of the intact group of animals (intact - 3.07 ± 0.25, inulin 2.99 - 3.14 ± 0.23, and BSP polysaccharide from the seeds of the turnip Brassica rapa 2.53-3.14 ± 0.20), while the indicator of the control group was - 8.40 ± 0.35. This study will provide an opportunity to plan and conduct studies to study the action of substances in the metabolism of glucose and lipids, which examines the enzymes that regulate the lipid activity of the liver, as well as the morphology of the liver and adipose tissue.

Green synthesis of titanium dioxide nanoparticles using Thymus vulgaris leaf extract for biological applications

In the last few decades, the biosynthesis of nanoparticles using biological agents such as microorganisms or plant extracts has gained a lot of attention due to the growing need for generating safe and non-toxic substances, cost-effective techniques, ecologically friendly solvents, and renewable materials. The aqueous leaf extract of Thymus vulgaris was used in the current investigation to achieve the biosynthesis of TiO2 nanoparticles (TiO2 NPs). In this study, leaf extract was used as a size-reducer in synthesis of TiO2. Thyme leaf extract contains flavonoids, phenols, and saponins, which function as both reducing and stabilising agents and are crucial for the synthesis of TiO2 nanoparticles. Methods such as Fourier-transform infrared spectroscopy (FTIR), ultraviolet-visible diffuse reflectance spectroscopy (UV-DRS), x-ray diffraction (XRD), photoluminescence (PL), and scanning electron microscopy (SEM) with energy dispersive x-ray (EDX) were used to characterise TiO2 NPs. The XRD investigations showed that titanium dioxide nanoparticles are crystalline and average crystal size is 28 nm. Gram-positive bacteria like S. aureus and B. subtilis as well as Gram-negative bacteria like Pseudomonas aeruginosa were used as standardised test microbial inoculums to evaluate the antibacterial properties of biosynthesised nanoparticles (TiO2 NPs). Against each of the studied bacteria, the TiO2 nanoparticles demonstrated significant antimicrobial activity. TiO2 nanoparticles had the maximum activity against Staphylococcus aureus, with an inhibitory zone diameter of 14 mm at 100 g ml−1. By using DPPH, hydroxyl radical techniques, the comprehensive antioxidant activity of produced NPs was examined.

Effect of citric acid on porcine plasma protein bioplastics processed through injection moulding

The replacement of petrochemicals by biopolymers in the production of plastics has some limitations, such as the poorer mechanical properties of the latter. Thus, when using porcine plasma protein (PPP) as raw material for developing bioplastics, the use of strengthening agents is required. Common additives currently used for that purpose, such as glutaraldehyde, negatively impact the biodegradability and toxicity of those materials. This study evaluates the effect of a green crosslinker like citric acid (CA) on PPP-based bioplastics. Therefore, using glycerol (gly) as a plasticizer, CA was added to the blend at different contents (0, 2.5, 5, 10%), either keeping the PPP/gly or (PPP + CA)/gly ratios at 1/1. Then, blends were injection moulded into biodegradable plastics, for which both mechanical properties and thermal stability improved as CA content was higher, as water absorption was hindered. However, it increased as CA content got higher, due to the acidification of the immersion media, but being always lower than the system without crosslinker. These findings suggest that citric acid, a natural, non-toxic, and abundant substance, could replace synthetic crosslinking agents in the development of PPP-based bioplastics.

Microbial remediation of oil-contaminated shorelines: a review.

Frequent marine oil spills have led to increasingly serious oil pollution along shorelines. Microbial remediation has become a research hotspot of intertidal oil pollution remediation because of its high efficiency, low cost, environmental friendliness, and simple operation. Many microorganisms are able to convert oil pollutants into non-toxic substances through their growth and metabolism. Microorganisms use enzymes' catalytic activities to degrade oil pollutants. However, microbial remediation efficiency is affected by the properties of the oil pollutants, microbial community, and environmental conditions. Feasible field microbial remediation technologies for oil spill pollution in the shorelines mainly include the addition of high-efficiency oil degrading bacteria (immobilized bacteria), nutrients, biosurfactants, and enzymes. Limitations to the field application of microbial remediation technology mainly include slow start-up, rapid failure, long remediation time, and uncontrolled environmental impact. Improving the environmental adaptability of microbial remediation technology and developing sustainable microbial remediation technology will be the focus of future research. The feasibility of microbial remediation techniques should also be evaluated comprehensively.

Production of the exopolysaccharide from Lactiplantibacillus plantarum YT013 under different growth conditions: optimum parameters and mathematical analysis

ABSTRACT Exopolysaccharides (EPSs) are highly heterogeneous natural polymers, can exhibit some unique bio-logical activities, such as anti-oxidation, inflammation regulation, anticancer and anti-viral activities, etc. A new type of EPS was obtained from the fermentation supernatant of Lactiplantibacillus plantarum YT013. However, the low yield of EPS posed a challenge for further research and application. Therefore, in this study, the production process of EPS was optimized, and anti-cancer cells proliferation activity was investigated. Identified the best single-factor conditions for EPS production, including initial pH 6, inoculation amount 5% (v/v), temperature 37°C, cultivation time 36 h, glucose 3% (w/v), soy peptone 1.5% (w/v), KH2PO4 0.3% (w/v). Under these conditions, the maximum production of EPS reached 0.630 mg/mL, which is 1.31 times higher than that before optimization. Concurrently, the nonlinear model was used for fitting, and it was found that the Voigt nonlinear model was in better agreement with the optimization results, which can be used as an effective tool for optimizing EPS production conditions. Furthermore, the anti-proliferative activity of EPS was evaluated using the human gastric cancer AGS cell line in vitro. MTT assay revealed a strong inhibitory effect of EPS on AGS cell proliferation. Additionally, flow cytometry analysis indicated that EPS promoted apoptosis in AGS cells. Lactiplantibacillus plantarum YT013 EPS, as a biodegradable and nontoxic natural active substance, shows potential as a natural antitumor substance.

STUDIES ON THE ACUTE TOXICITY OF THE EXTRACTS OF GENTIANA ASCLEPIADEA L

The search and creation of new medicinal products based on plant raw materials is one of the important tasks of medicine and pharmacy. Toxicological studies are an important stage in the development of new medicinal products. Studies on the acute toxicity make it possible to obtain information about the danger of the studied drug in the conditions of short-term studies and the prospects for conducting further tests.
 Gentiana (G.) asclepiadea, which has long been used in traditional medicine, is promising for research and further creation of medicinal products.
 The aim is to study the acute toxicity of liquid and thick extracts of Gentiana asсlepiadea roots.
 Materials and methods. The objects of the study were liquid and thick extracts of the roots of G. аsсlepiadea, which were obtained from the crushed roots by the method of remaceration with 40% ethanol, followed by evaporation for a thick extract.
 The acute toxicity of G. asсlepiadea roots extracts in order to determine the LD50 was studied in accordance with the methodological recommendations of the State Pharmacological Center of the Ministry of Health of Ukraine on male mice by a single intragastric injection. The animals were divided into four groups of 6 animals each. Animals of group I (intact animals) were given drinking water; animals of the II group were injected with 40 % ethanol; animals of III and IV groups were injected with liquid and thick extracts of G. asсlepiadea roots, respectively. The studied extracts, 40 % ethanol and drinking water were injected intragastrically at a dose of 25 ml/kg.
 The animals were observed for 14 days. The degree of toxicity of the extracts was assessed by changes in the general condition of the animals, lethality, the effect of the extract on the dynamics of the body weight of the animals, macroscopic signs of internal organs, their mass coefficients were calculated, hematological and some biochemical blood parameters were determined.
 Results of the research. No deaths of animals were noted, appearance and behavioral reactions did not differ from intact animals with a single intragastric injection of G. asсlepiadea roots extracts at a dose of 25 ml/kg. During the observation period, there was a physiological increase in the body weight of the animals relative to the initial data. Macroscopic examination of the internal organs of animals revealed no pathological changes, the mass coefficients of internal organs did not differ from intact animals, which indicates the absence of hepatotoxic and nephrotoxic effects when taking extracts of G. asсlepiadea. The lack of toxic effect of G. asсlepiadea extracts is confirmed by hematological and biochemical indicators, since the number of leukocytes, erythrocytes, hemoglobin level, activity of ALT and AST in the blood of the animals of the experimental groups were within the parameters of intact animals.
 Thus, the maximum administered dose of the liquid root extract of G. asclepiadea in terms of dry matter was 5015 mg/kg, and the thick root extract was 5000 mg/kg.
 Conclusions. According to the results of the study of acute toxicity of liquid and thick extracts of the roots of G. asclepiadea when administered intragastrically to male mice in doses of 25 ml/kg and 5000 mg/kg, respectively, it was established that they have no toxic effect. This means that the studied extracts of the roots of G. asclepiadea can be attributed to practically non-toxic substances (toxicity class V, LD50 > 5000 mg/kg), according to the classification of substances by toxicity.

Preclinical evaluation of a gel composition based on a flavonoid complex for the treatment of periodontal diseases in orthodontic patients

The aim of the work was a preclinical assessment of acute toxicity, skin resorptive, irritant effects, cumulative and catalase activity, as well as sensitizing properties of the local gel composition “Benzidaflaziverdine” (GCB) used for the treatment of periodontal diseases in orthodontic patients. Materials and methods. 119 animals were involved in the experiment, assigned to seven main and two control groups. GCB was administered intragastrically in doses of 300–600 mg/kg and intradermally of 200 μg into the outer surface of the ear. The native solution of GCB was applied to the skin and mucous membranes, administered orally by the method of “subchronic toxicity” and to the surface of the chorioallantoic membrane (CAM) of chicken embryos. The intensity of lipid peroxidation (LPO) was assessed by the level of diene conjugates (DCs) and malondialdehyde (MDA), and the antioxidant system by catalase activity. The specific leukocyte agglomeration reaction (SLAR), the specific leukocyte lysis reaction, and neutrophil damage indicators were used. Results. The median lethal dose LD50 for rats and mice of both sexes exceeded 5000 mg/kg. The irritant effect of GCB on the mucous membranes was manifested by hyperemia on the second day. Symptoms of irritation disappeared after 3–4 days without medical intervention. An analysis of the CAM blood vessels after exposure to GCB in two observations at the 120th second showed the beginning of hemorrhages. In one observation, GCB caused minor hemorrhages at the 300th second of the experiment. It was found that the coefficient of GCB irritant action was 5 (the mean score of Me (Q1; Q3) was 5 (4; 5)). The coefficient of cumulation (Kcum) exceeded 8.2. An insignificant increase in the median or mean values of catalase enzyme activity, DCs, and the amount of LPO end product such as MDA was observed compared to the control group animals. The SLAR test indicated the development of a delayed-type allergic reaction under the influence of GCB in a 1:10 dilution. One-hundred-fold dilution did not cause significant changes in the indicator in the main group compared to the control one. Conclusions. GCB belongs to the 4th class of toxicity – practically non-toxic substances, does not have sex- and species sensitivity, has weak cumulative activity, minimal effect on the system of LPO. GCB can be recommended for the use in clinical periodontology for medical support of orthodontic patients.