scholarly journals EXPERIMENTAL EVALUATION OF HEPATOPROTECTIVE ACTIVITY OF A NEW COMPOSITION OF OXIMETHURACIL WITH CARBONIC ACIDS

2019 ◽  
Vol 98 (9) ◽  
pp. 1004-1010
Author(s):  
E. F. Repina ◽  
D. O. Karimov ◽  
G. V. Timasheva ◽  
N. Yu. Khusnutdinova ◽  
A. R. Gimadieva ◽  
...  

Introduction. The high frequency of chemical poisoning is accompanied by an increase in the absolute number of cases of chemical damage to the liver. There is growing evidence that acute chemical poisoning in Russia is among the leading non-infectious diseases leading to premature death of male and female working-age people. It seems relevant to search for new pharmacological agents with low toxicity and high hepatoprotective activity, which increase the body’s stability under the influence of adverse environmental factors. The use of metabolic action drugs combining antioxidant and antihypoxic activity as hepatoprotectors is promising. The purpose of this study is an experimental evaluation of the hepatoprotective activity of a new composition of oxymethyluracil with succinic and fumaric acids. Material and methods. The composition of 5-hydroxy-6-methyluracil with succinic and fumaric acids was first synthesized at the Ufa Institute of Chemistry. Using the model of acute liver toxic damage with carbon tetrachloride in laboratory animals, the prophylactic effect of a new drug was studied in comparison with heptor (ademetionine). Biochemical and morphological studies of laboratory animals’ biomaterial were conducted. Results. The analysis showed that when using the studied drugs, biochemical parameters were close to the level of control animals. Morphological changes in the liver were less pronounced in the group of animals treated with the new composition, compared with changes in the structure of the liver of animals treated with heptorator (ademetionin). Conclusion. The new composition of 5-hydroxy-6-methyluracil with succinic and fumaric acids has a protective effect on the liver of laboratory animals with the acute toxic effects of carbon tetrachloride, comparable, and in some cases, exceeding the preventive effect of heptoperam (ademetionine).

2020 ◽  
Vol 99 (9) ◽  
pp. 1001-1006
Author(s):  
Elvira F. Repina ◽  
Denis O. Karimov ◽  
Samat S. Baygildin ◽  
Gulnara V. Timasheva ◽  
Nadezhda Yu. Khusnutdinova ◽  
...  

Introduction. Among noninfectious diseases, one of the leading places belongs to pathologies caused by the action of industrial toxicants. In this regard, the search for drugs for the prevention and treatment of various intoxications is one of the priority tasks of public health. Treatment of intoxication with drugs with antioxidant and antihypoxic activity is more effective. The aim of this study was to investigate morphological changes in parenchymal organs (liver, kidneys, and pancreas) under acute exposure to high doses of carbon tetrachloride and to evaluate the effectiveness of their correction with a new composition of oxymethyluracil with ascorbic acid. Material and methods. The composition of 5-hydroxy-6-methyluracil with ascorbic acid was first synthesized at the Ufa Institute of Chemistry, Ufa Federal Research Center, RAS. The preventive effect of the new drug was studied in comparison with “Heptor” on the carbon tetrachloride-induced liver injury model. Morphological studies of the liver, pancreas, and kidneys of laboratory animals were carried out. Results. Studies have shown the prophylactic administration of new composition of 5-hydroxy-6-methyluracil with ascorbic acid to have a protective effect on the structure of parenchymal organs in acute carbon tetrachloride intoxication, comparable to the drug “Heptor” (possibly superior). However, reparative properties were observed only in the drug “Heptor”. Conclusion. Comparative estimation of morphological changes in parenchymal organs under acute exposure to high doses of carbon tetrachloride indicates the protective effect of prophylactic administration of the composition of 5-hydroxy-6-methyluracil with ascorbic acid, comparable to the drug “Heptor” (possibly superior).


Author(s):  
Е. F. Repina ◽  
D. O. Karimov ◽  
G. V. Timasheva ◽  
N. Yu. Khusnutdinova ◽  
L. A. Musina ◽  
...  

The article presents the results of morphological changes in the liver of rats after acute liver injury induced by carbon tetrachloride and prophylactic correction of injuries by combinations of oxymethyluracil with different types of medical products: «Mexidol», «Tonarol» and Acetylcysteine. The best corrective effect was established after applying a combination of oxymethyluracil with «Tonarol». Thus, according to the results obtained, the studied drugs combinations can be arranged in the following sequence in accordance with decreasing of hepatoprotective activity: OMU / «Tonarol» > OMU / Acetylcysteine> OMU / «Mexidol».


Author(s):  
O. V. Pelypenko

Every fifth inhabitant of the earth has been diagnosed with osteoarthritis of various etiologies. Morphological studies of arthritis provide a theoretical basis for creating optimal treatments for this pathology. Given the polyetiological nature of the disease, the choice of the optimal experimental model, which would be as close as possible to the real conditions of inflammatory process reproduction, is the topical issue. The purpose of the study was to confirm the pathological reaction of the joint tissues of laboratory animals in response to intraperitoneal administration of ƛ-carrageenan. The study was performed on 50 white Wistar rats males aged 12 weeks, weighing 130-150 g. The animals were euthanized by an overdose of anaesthesia according to the terms of the study (1 - 30 days). Fragments of the distal metaepiphyses of the femur and proximal metaepiphyses of the tibia were used for histological examination. Staining of sections obtained on the microtome was performed with haematoxylin, eosin, and Van Gieson`s stain. From the first day of the experimental study, a corresponding reaction of the joint tissues was being observed. Particularly pronounced were the changes in the synovial membrane in the form of oedema of the villi accompanied by an increased filling of blood vessels with foci of thrombosis. Gradually, up to 5 days in the synovial membrane, proliferative changes took place with a clear definition of the multilineage of the integumentary layer, vascular reaction with a tendency to thrombosis, in some places necrosis of synoviocytes was observed, but relative integrity of the morphological structure was still provided by protective barriers of bone and cartilage. On the 7th day pronounced resorption of both bone and cartilage tissue occurred, tissue structure became disorganized and functional layer became thin, accompanied by massive intracellular lysis. The process of synoviocytes necrobiosis with fatty degeneration spread. The histological picture of 10 days is characterized by generalized destruction of bone beams; the destroyed cartilage was replaced by granulation tissue with the presence of cavities. Massive foci of lymphocytic infiltration were observed in the synovial membrane. On the 14th day, a fragmentation of cartilage happened, most of the bone beams (trabeculae) were destroyed. After 3 weeks the morphological picture of cartilage tissue was determined by the appearance in the lacunae of viable cells, the number of which was close to normal. Bone beams were restored, although they remained thin. In a synovial membrane, the hyperplasia of apical departments of villi, leukocytes infiltration, disorganization of connective tissue, and separate vascular disturbances remained. 30 days of the experiment were characterized by a relative recovery of structural relationships to normal. The obtained data confirm the feasibility of using carrageenan in experimental studies of osteoarthritis.


Author(s):  
Semeleva E.V. ◽  
Blinova E.V. ◽  
Zaborovsky A.V. ◽  
Vasilkina O.V. ◽  
Shukurov A.S.

In this work, we studied the pharmacological activity of zinc and magnesium salts of 2-aminoethanesulfonic acid in white non-linear male rats with amyotrophic lateral sclerosis, which was modeled by neurotoxicantsimplication into the pelvic part of spinal cord. After the reproduction of the pathology in animals, the indices of motor activity were recorded in the Rotarod test, and morphological studies of spinal cord sections stained according to Nisl in the Belshovsky modification were carried out. It was shown that the magnesium salt of 2-aminoethanesulfonic acid (compound LHT-317) to a greater extent reduces the development of motor disorders in experimental animals compared with the control group on the 4th day of observation. The course of intravenous administration of the studied compounds of 2-aminoethanesulfonic acid did not inhibit morphological changes in the spinal cord that develop in degenerative-dystrophic pathology of the central nervous system: connections. Moreover, if, against the background of treatment with zinc salt, the total area of motor zones in animals of the experimental group exceeded that of control rats, then the number of motoneurons did not differ from the control.


Author(s):  
Sergey Staroverov ◽  
Sergey Kozlov ◽  
Alexander Fomin ◽  
Konstantib Gabalov ◽  
Alexey Volkov ◽  
...  

Background: The liver disease problem prompts investigators to search for new methods of liver treatment. Introduction: Silymarin (Sil) protects the liver by reducing the concentration of free radicals and the extent of damage to the cell membranes. A particularly interesting method to increase the bioavailability of Sil is to use synthesized gold nanoparticles (AuNPs) as reagents. The study considered whether it was possible to use the silymarin-AuNP conjugate as a potential liver-protecting drug. Method: AuNPs were conjugated to Sil and examine the liver-protecting activity of the conjugate. Experimental hepatitis and hepatocyte cytolysis after carbon tetrachloride actionwere used as a model system, and the experiments were conducted on laboratory animals. Result: For the first time, silymarin was conjugated to colloidal gold nanoparticles (AuNPs). Electron microscopy showed that the resultant preparations were monodisperse and that the mean conjugate diameter was 18–30 nm ± 0.5 nm (mean diameter of the native nanoparticles, 15 ± 0.5 nm). In experimental hepatitis in mice, conjugate administration interfered with glutathione depletion in hepatocytes in response to carbon tetrachloride was conducive to an increase in energy metabolism, and stimulated the monocyte–macrophage function of the liver. The results were confirmed by the high respiratory activity of the hepatocytes in cell culture. Conclusion: We conclude that the silymarin-AuNP conjugate holds promise as a liver-protecting agent in acute liver disease caused by carbon tetrachloride poisoning.


2001 ◽  
Vol 53 (11) ◽  
pp. 1569-1574 ◽  
Author(s):  
M. P. Germanò ◽  
V. D'Angelo ◽  
R. Sanogo ◽  
A. Morabito ◽  
S. Pergolizzi ◽  
...  

2021 ◽  
Author(s):  
Brilliance Onyinyechi Anyanwu ◽  
Anthonet N. Ezejiofor ◽  
Ify L. Nwaogazie ◽  
Orish Ebere Orisakwe

Abstract Technological developments have led to exposure to various substances that are harmful to the environment and public health, including heavy metals. In the environment, these grades of metals are usually diverse mixtures shown to cause physiological, biochemical and neurological dysfunctions in humans and laboratory animals. Cadmium, Lead, and mercury have been envisaged to exhibit their hepatotoxic effects by oxidative induction damage and synthesis of reactive oxygen species (ROS). The current work evaluated the protective activity of aqueous leaf extract of Costus afer (ALECA)) on liver damage arsing from exposure to trace metal mixture (TMM): cadmium chloride (CdCl2), lead chloride (PbCl2), and mercury chloride (HgCl2). Five groups of weight matched Sprague Dawley rats were treated for 90 days. Metal mixture and deionized water were used to treat the 2 groups of rats whereas the other 3 groups were treated with various doses of the ALECA through oral gavage alongside the metal mixture. Hepatic function parameters, oxidative biomarkers, inflammatory cytokines, Morphological changes and trace metals (concentrations were monitored in the liver). TMM treatment resulted in significant increase in ALT, AST, ALP, bilirubin, IL-6, MDA, but decreased albumin, total protein, IL-10, SOD, CAT and GSH levels. TMM also caused some morphological changes and increased the heavy metal (Pb, Cd and Hg) concentrations in the liver. The leaf extract gave a reasonable protective effect on the hepatotoxicity caused by trace metal mixture - through the mechanisms of metal chelation, anti-inflammatory, and antioxidant although this depends on the dosage to the rats. ALECA may be beneficial in the management of liver toxicity.


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