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

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.

2021 ◽  
Vol 29 (2) ◽  
pp. 69-71
Author(s):  
V. I. Korzhov ◽  
◽  
B. O. Osipenko ◽  
M. P. Budennaya ◽  
M. G. Palivoda

Experimental studies are among the important and promising approaches in the studying of the pathogenesis of pulmonary emphysema (PE). They make it possible to trace and understand the sequence of metabolic disorders wich occur in this condition. The aim of the trial was to study the nature of biochemical changes in blood plasma during the course of experimental PE. Materials and methods. The study was carried out on 36 sexually mature, outbred, white rats of both sexes, weighing 180-200 g, which were kept on a standard vivarium diet. Experimental papain PE in white rats was induced by a single intratracheal administration of 0.5 ml of papain solution (Merck KGaA, Germany) at a dose of 100 mg / kg body weight under light ether anesthesia. The rats were withdrawn from the experiment by decapitation under light ether anesthesia 10, 20, 30, 50 and 60 days after the onset of the disease. Biochemical studies of blood plasma - the content of alanine aminotransferase (ALT), aspartate aminotransferase (AST), protein, urea, creatinine, total bilirubin, glucose were carried out using automatic biochemical analyzer Selectra Pro-M (Netherlands). Results. It was found that 10 days after the onset of the disease, the levels of ALT and AST significantly decreased by 37%. The trend towards a decrease in ALT persisted after 20, 30 and 60 days; AST � after 20, 30, 50 and 60 days. It was found that the blood plasma protein significantly decreased 10 and 20 days after the onset of the disease by 33% and 38%, respectively. At the same time, the urea also decreased after 10 days by 36% and by 32% after 20 days. A similar trend of changes was found when studying the level of creatinine in blood plasma. After 10 and 20 days, creatinine decreased by 36% and 37%, respectively. As for total bilirubin, its blood plasma contentration increased by 68% after 10 days, and by 38% after 20 days. There were no changes in plasma glucose levels 10, 20, 30, 50 and 60 days after the onset of the disease. Conclusions. Experimental PE is characterized by the most pronounced changes in blood plasma biochemical parameters 10 and 20 days after the onset of the disease, which is manifested by a decrease of aminotransferases � ALT and AST, a decrease in total protein, urea, creatinine, and an increase of total bilirubin. Key words: experimental pulmonary emphysema, alanine aminotransferase, aspartate aminotransferase, protein, urea, creatinine, bilirubin, glucose. U


10.23856/4626 ◽  
2021 ◽  
Vol 46 (3) ◽  
pp. 202-207
Author(s):  
Svitlana Anokchina ◽  
Olena Yasinska

The aim of our scientific work was to study the effect of exogenous melatonin on the indicators of fibrinolytic processes in the heart tissues and to analyze the changes in fibrinolytic activity occurring in the heart tissues of enucleated hyper- and hypothyroid white rats. The experiments were carried out on white nonlinear male rats weighing 0.12-0.14 kg. 4 experimental groups of animals were formed. The control group consisted of 11 normothyroid rats, which were injected with a melatonin solution in appropriate volumes. The animals were euthanized under light ether anesthesia. Samples of the examined heart tissue were ground in a glass homogenizer with borate buffer (pH 9.0). The homogenate was used in biochemical analysis. Determination of the total, enzymatic and non-enzymatic fibrinolytic activity (TFA, EFA, NFA, respectively) in the heart tissues was carried out by the method of azofibrin lysis (LLC "Simko", Ukraine). Statistical processing of the results was carried out by the method of variation statistics using the Student's test. Experimental studies on nonlinear male white rats have shown that the introduction of exogenous melatonin, as well as modeling the conditions of endogenous melatonin overproduction by blinding (enucleation) cause an increase in the intensity of enzymatic and non-enzymatic fibrinolysis in heart tissue in normotyroid animals. At other hand, enucleation causes an increase in the intensity of fibrinolysis in the tissues of the heart in hypothyroid rats, but not in hyperthyroid.


2020 ◽  
Vol 101 (1) ◽  
pp. 40-46
Author(s):  
G A Bayburina

Aim. To characterize the peculiarities of the dynamics of the level of corticosteroid receptors in the myocardium of animals with different resistance to hypoxia in the post-resuscitation period. Methods. Experimental studies were carried out on male non-inbred white rats, divided into 2 groups by hypoxia resistance. A 5-minute arrest of the systemic circulation was modeled under ether anesthesia with intrathoracic clamping of the cardiovascular cluster with subsequent resuscitation. The observation period was 35 days. The content of corticosterone and aldosterone was determined in the blood plasma, the concentration of glucocorticoid and mineralocorticoid receptors in myocard homogenates was determined as well. Results. On days 1 to 3 of the post-resuscitation period in rats highly resistant to hypoxia, the dynamics of plasma corticosterone concentration and the content of corticosteroid receptors was unidirectional. Starting from the 5th day, against the background of a statistically significant decrease in the level of plasma corticosterone, a gradual increase in the density of corticosteroid receptors, mostly glucocorticoid, was observed, most pronounced on the 14th day and remaining until the end of the observation. In animals with low resistance to hypoxia, the dynamics of corticosteroid receptors was characterized by a predominance of mineralocorticoid content in almost all periods of observation. On days 13 of post-resuscitation period on the background of high concentrations of corticosteroid hormones, the minimum content of glucocorticoid receptors was noted. A decrease in the mineralocorticoid receptor level was recorded only on the first day, and in all subsequent periods of the experiment, the control indicators were significantly higher by 1.41.6 times. Strengthened mineralocorticoid signaling in the myocardium, characteristic of animals with low resistance to hypoxia, may be associated with the development of hypertrophy and fibrosis, inflammation, impaired electrical function. An increase in glucocorticoid receptors, characteristic of animals with a high resistance to hypoxia, has an adaptive effect, limiting the inflammatory response, the potential mechanism may be associated with increased expression of type 11-hydroxysteroid dehydrogenase. Conclusion. The identified features can have a significant influence on the course of the post-resuscitation period and determine the long-term forecast.


Author(s):  
B.A. Katsnelson ◽  
M.P. Sutunkova ◽  
L.I. Privalova ◽  
S.N. Solovjeva ◽  
V.B. Gurvich ◽  
...  

The article presents in an experiment obtained principal results based on repeated low-level inhalation exposures of laboratory animals (white rats, outbred) to nickel oxide nanoparticles with a diameter of (23 ± 5) nm, 4 hours a day, 5 times a week for up to 10 months in a «nose only» installation. It was shown that non-specific body reactions to the action of NiO NPs include: diverse manifestations of systemic toxicity with a particularly pronounced influence on liver and kidney function, redox balance, damage to some areas of brain tissue, associated with proven movement of the nanoparticles themselves from the nasal mucosa along the olfactory tract; some cytological signs of probable development for allergic syndrome; paradoxically low severity of pulmonary pathology by pneumoconiotic type explained by a small chronic delay of nanoparticles in the lungs; the genotoxic effect of the organismal level, even at those low levels of chronic exposure, at which systemic toxicity is rather poorly. Along with that, NiO NPs also induce phase-stimulation of erythropoiesis, which is relatively specific for the toxic nickel effects.


1996 ◽  
Vol 318 (2) ◽  
pp. 489-495 ◽  
Author(s):  
Julia KAROW ◽  
Keith R. HUDSON ◽  
Mark A. HALL ◽  
Ann B. VERNALLIS ◽  
Jacky A. TAYLOR ◽  
...  

Interleukin-11 (IL-11) is a polyfunctional cytokine whose biological actions require a specific IL-11 receptor (IL-11R) and the transmembrane transducer gp130. Here we report the production of a soluble form of the murine IL-11R and demonstrate that it interacts with IL-11 ligand with high affinity. The affinity of IL-11 alone for gp130 is below the level of detection, but a complex of IL-11 and soluble IL-11R interacts with gp130 with high affinity. The addition of soluble IL-11R potentiates the effects of exogenous IL-11 in cells that are normally responsive to IL-11. A biological response to IL-11 can be reconstituted in BAF cells transfected with gp130 by addition of IL-11 and soluble IL-11R. These findings show that the cytoplasmic domain of the IL-11R is not required for the biological effects of IL-11 and that a complex of IL-11 and IL-11R mediates signalling by association with gp130.


1920 ◽  
Vol 32 (5) ◽  
pp. 601-625 ◽  
Author(s):  
Hideyo Noguchi ◽  
I. J. Kligler

Injections into guinea pigs of the blood and the emulsions of liver and kidney obtained at autopsy from a fatal case of yellow fever in Merida induced in some of these animals, after a period of several days incubation, a rise of temperature which lasted 1, 2, or more days. When killed for examination at this febrile stage the animals invariably showed hemorrhagic areas of various size, sometimes few and sometimes numerous, in the lungs, and also, though less constantly, in the gastrointestinal mucosa, together with general hyperemia of the liver and kidneys. In a guinea pig (No. 6) inoculated with the liver emulsion of Case 1 there was a trace of jaundice on the 9th day. Injections of the blood or liver and kidney emulsions from such animals into normal guinea pigs reproduced the febrile reactions and the visceral lesions. The majority of the animals which were allowed to live and complete the course of the infection rapidly returned to normal (within several days). Examinations of these surviving guinea pigs after 2 weeks revealed the presence of rather old hemorrhagic foci in the lungs. In the course of further attempts to transfer the passage strain, a secondary infection by a bacillus of the paratyphoid group caused many deaths among the guinea pigs and resulted finally in the loss of the strain from Case 1. Most of the cultures made with the heart's blood taken at autopsy from Case 1 proved to be contaminated with a bacillus of the coli group. The contents of the apparently uncontaminated tubes were inoculated into guinea pigs, but the results were for the most part negative or vitiated by a secondary infection. Dark-field search for the leptospira with the autopsy materials was negative, although prolonged and thorough examination was not practicable at the time of these experiments. Our efforts were concentrated on obtaining positive animal transmission rather than on the time-consuming demonstration of the leptospira, which when unsuccessful does not necessarily exclude the presence of the organism in small numbers. Likewise, the dark-field work with the material from guinea pigs was confined to a brief examination and was omitted in many instances. Under these circumstances no leptospira was encountered in any of the material from Case 1. On the other hand, the results obtained with the specimens of blood from Case 2 were definitely positive, not only in the transmission of the disease directly, or indirectly by means of cultures, into guinea pigs, but also in the demonstration of the leptospira in the primary cultures and in the blood and organ emulsions of guinea pigs experimentally infected with such cultures. Definite positive direct transmissions were obtained with the specimens of blood drawn on the 2nd and 3rd days. No blood was taken on the 4th or 6th days. There were indications of abortive or mild leptospira infection in the guinea pigs inoculated with the blood taken on the 5th day. Regarding the inoculation of cultures from Case 2, it may be stated that only the cultures (leptospira +) made with the blood drawn on the 2nd day caused a definite fatal infection in guinea pigs. From this series a continuous passage in the guinea pig has been successfully accomplished. One of the guinea pigs (No. 48) inoculated with the culture 5 days old (leptospira +) made from the blood taken on the 3rd day presented typical symptoms, and a positive transfer from this to another animal (No. 98) was also made. Cultures of the blood drawn on the 5th and 7th days gave unsatisfactory results, owing to a secondary contamination. Leptospiras were detected in some of the culture tubes containing 2nd and 3rd day specimens of blood from Case 2; they were few in number and for the most part immotile, owing perhaps to some unfavorable cultural condition such as a fungus contamination. Charts 17, 18, and 19 give a summary of the experiments. See PDF for Structure


2021 ◽  
Vol 12 (4) ◽  
Author(s):  
B. V. Borysevych ◽  
◽  
V. V. Lisova ◽  
I. M. Derkach ◽  
S. S. Derkach ◽  
...  

Iron (IV) clathrochelate based on a macrobicyclic ligand of the hexahydrazide type is a unique compound that contains iron in a rare high valence IV. Preclinical and clinical studies of this complex, which were started for the first time in Ukraine, have an important theoretical and practical consequence as this complex can be recommended as an active substance in iron-containing drugs with antianemic action. In conducting preclinical studies of new drugs, pathomorphological studies are important because they are a necessary step in studying the biological response of animals to the action of test substances. It was found that some pathological changes develop in the body of white mice under conditions of experimental acute and chronic iron (IV) clathrochelate intoxication. They correlated with the dose of the test compound. During chronic intoxication, the microscopic changes in the liver and kidney of white mice treated with iron (IV) clathrochelate at a dose of 1/10 DL50 were similar to the microscopic changes in the liver and kidney of mice treated with the experimental drug at a dose of 1/5 DL50. However, the severity of these changes was lower, reflecting a lower degree of organ damage. In the myocardium of mice treated with iron (IV) clathrochelate at a dose of 1/5 DL50 on the 10th day, as in acute iron (IV) clathrochelate poisoning, only edema was recorded. The prospects for further research are the study of microscopic changes in the organs of laboratory animals of other species during experimental iron (IV) clathrochelate toxicosis.


2021 ◽  
Vol 1 (1) ◽  
pp. 72-78

The article presents the results of laboratory studies to assess the toxicological parameters of montmorillonite clay from the Pogadaevskoye deposit in the West Kazakhstan region in order to use them as an aluminosilicate sorbent in the composition of feeds that reduce the negative effects of mycotoxins on the body of animals and birds. The relevance of research is associated with the cultivation of healthy and highly productive animals and poultry in order to ensure the food security of the Republic of Kazakhstan.The studies carried out to assess the toxicological parameters of montmorillonite clay in order to use them as an aluminosilicate sorbent in experimental animals (rabbits and white rats) allowed the following results to be obtained: Visual study of the intensity of erythema when exposed to the test substance on the skin of rabbits showed their absence (0 points). The study of the intensity of edema (an increase in the thickness of the skin clutch of rabbits) when exposed to the test substance on the skin of rabbits showed no reaction (0 points). Studies evaluating the irritating effect of the test substances on the mucous membranes of the eyes of rabbits by symptoms of damage showed the absence of hyperemia (0 points). Weak eyelid edema (1 point), the minimum amount of discharge in the corner of the eye (1 point). The results of studies on the classification assessment of the test substance for the severity of the irritant effect on the eyes of rabbits showed that the average total score of the severity of the irritative effect corresponds to 1 point. A comprehensive analysis of the results obtained on the basis of scientific and experimental studies to assess the toxicological indicators of montmorillonite clay from the Pogadaevskoye deposit in relation to irritating effects on the skin and mucous membranes of experimental animals (rabbits) showed their harmlessness.


2020 ◽  
Vol 98 (Supplement_2) ◽  
pp. 21-22
Author(s):  
Wayne Zeller

Abstract As a class of plant polyphenolic compounds contained in some forages [i.e., sainfoin (Onobrychis viciifolia Scop.), big trefoil (Lotus pedunculatus Cav.), birdsfoot trefoil (Lotus corniculatus L.)], condensed tannins (CTs) exhibit a variety of biological effects on ruminants. The potential positive impact of CTs on the agricultural industry stems from their ability to modulate proteolysis during forage conservation and ruminal digestion, to prevent bloat, to reduce intestinal parasite burdens, and to abate methane and ammonia emissions from ruminants. How CTs exert these effects on ruminants focuses on the interaction of CTs with proteins. The structure-activity relationship in CT–protein interaction is not well understood but is known to be dependent on the structure and properties of both the CT and the protein. The objectives of this presentation are fivefold. First, examples of the structural diversity of CTs will be provided to enable the audience members to appreciate that not all CTs are the same. Second, examples of how CTs structural diversity affects their interaction with the protein, which in turn, dictates the biological response from the animal will be discussed. Third, the presentation will outline hurdles in obtaining highly pure and well-characterized CTs from natural sources for use in CT structural analysis and in vitro experiments. This will be followed by brief descriptions of improved and emerging techniques for CT analysis and, finally, the presentation concludes with questions to address in future investigations and a list of recommendations for CT researchers to follow.


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