scholarly journals Metabolic changes on the background of acute exposure to paracetamol and evaluation of the effectiveness of hepatoprotective drug

2020 ◽  
Vol 99 (9) ◽  
pp. 1016-1021
Author(s):  
Gulnara V. Timasheva ◽  
D. O. Karimov ◽  
E. F. Repina ◽  
D. A. Smolyankin ◽  
N. Yu. Khusnutdinova ◽  
...  

Introduction. In modern conditions, caused by the pandemic of a new type of viral infection Covid 19, the use of paracetamol, which has hepatotoxic properties in overdose, has increased. It seems relevant to study metabolic disorders in the liver in acute paracetamol intoxication and evaluate the effectiveness of the timely use of hepatoprotective drugs. The purpose of this study is an experimental assessment of metabolic changes at the early stages of paracetamol exposure and pharmacological correction of toxic liver lesions with oxymethyluracil in comparison with known hepatoprotectors - ademetionine and Mexidol. Material and methods. Acute intragastric administration of paracetamol to laboratory animals was performed, and the corrective effect of the drug oxymethyluracil was studied in comparison with “Heptor” and “Mexidol”. Biochemical studies of biomaterial of laboratory animals were conducted. Results. The analysis found the use of known hepatoprotectors and oxymethyluracil after exposure to paracetamol to normalize the biochemical parameters that characterize the functional state of the liver in laboratory animals. Conclusion. Oxymethyluracil, along with known hepatoprotectors, has a protective effect on the liver of laboratory animals under acute exposure to paracetamol comparable to, and in some cases exceeding, the corrective action of “Heptor” and “Mexidol”.

2021 ◽  
Vol 100 (11) ◽  
pp. 1287-1291
Author(s):  
Ahat B. Bakirov ◽  
Elvira F. Repina ◽  
Denis O. Karimov ◽  
Samat S. Baigildin ◽  
Alfiya R. Gimadieva ◽  
...  

Introduction. Considering the prevalence of acute alcohol poisoning in Russia, it seems urgent to search for new effective means of correcting them. Along with taking measures to remove ethanol from the body, pathogenetic correction is effective. Oxymethyluracil and its derivatives have proven to be effective hepatoprotectors in various experimental models of liver damage. The aim of the research was the evaluation of the effectiveness of oxymethyl uracil on the model of acute alcohol intoxication. Material and methods. On the model of acute toxic liver injury of laboratory animals with ethanol, the efficiency of correction of pathological changes with oxymethyl uracil was studied compared to the drug “Mexidol”. A complex of biochemical, morphological and genetic studies was carried out. Results. The morphological studies showed that the correction with oxymethyluracil was more effective at both time points than the drug “Mexidol”, which was manifested in a lower intensity of damage to the liver parenchyma. In the group that received oxymethyluracil, a restoration of the frequency of expression of the Chek 1 gene was observed both after 24 and 72 hours. Upon acute exposure to ethanol, a slight decrease in the level of RIPK1 gene expression was observed. The level of expression of this gene decreased most significantly during the correction of oxy methyl uracil. A decrease in the frequency of expression of this gene can indicate a slowdown in necrosis processes and suppression of reactive oxygen species production in liver cells and, consequently, a curative effect of oxymethyluracil in this type of intoxication. Conclusion. Based on the complex biochemical, morphological and genetic studies carried out, it can be concluded that under acute exposure to ethanol, the corrective effect of oxymethyl uracil is more pronounced than Mexidol (ethylmethylhydroxypyridine succinate).


Author(s):  
Gulnara Vilievna Timasheva ◽  
Denis Olegovich Karimov ◽  
Elvira Faridovna Repina ◽  
Denis Anatolievich Smolyankin ◽  
Nadezhda Yurievna Khusnutdinova ◽  
...  

Paracetamol is one of the most widely used and popular over-the-counter analgesics and antipyretic drugs in the world. The number of registered cases of paracetamol-induced liver intoxication is constantly increasing in the world every year. It seems relevant to study early metabolic disorders in the liver in acute paracetamol intoxication and assess the effectiveness of the timely use of hepatoprotective drugs. The aim of this research is to study metabolic changes in laboratory animals at the early stages of exposure to paracetamol and against the background of correction with oxymethyluracil, ademetionine and mexidol. An experimental study of metabolic changes in laboratory animals under acute exposure to toxic doses of paracetamol and against the background of correction was carried out. Biochemical parameters in the blood serum of laboratory animals were investigated. The obtained results showed that the intake of paracetamol in toxic doses was accompanied by impaired hepatic metabolism at the earliest stages of exposure. With the corrective action of the studied drugs, metabolic disturbances caused by paracetamol intoxication were restored. At the same time, OMU, as well as ademetionine and ethylmethylhydroxypyridine succinate, is able to normalize metabolic changes after the acute toxic effect of paracetamol, and has a pronounced advantage in terms of the protein-synthetic function of hepatocytes.


2016 ◽  
Vol 31 (3) ◽  
pp. e3814 ◽  
Author(s):  
Shihui Bao ◽  
Jing Zhang ◽  
Zixia Lin ◽  
Ke Su ◽  
Jingjing Mo ◽  
...  

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).


2021 ◽  
Vol 23 (103) ◽  
pp. 109-115
Author(s):  
L.-M. Kostyshyn ◽  
R. Sachuk ◽  
Ye. Kostyshyn ◽  
O. Katsaraba

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.


2020 ◽  
Vol 87 (9-10) ◽  
pp. 84-88
Author(s):  
R. I. Vynogradov ◽  
O. S. Tyvonchuk ◽  
K. O. Nadiein ◽  
V. V. Moskalenko

Objective. To study metabolic changes and peculiarities of mineral balance depending on the common loop length while constructing of the simulated model of gastric shunting with one anastomosis during 60 days. Materials and methods. Experimental simulation of gastric minishunting with one anastomosis of various length of bilio-pancreatic loop was constructed on the rats. In 10 rats the anastomosis was formatted on level of half of total length of small intestine (Group I), and also in 10 - a third part of general length of small intestine (Group II). Control Group consisted of 5 rats. The indices of the extra body mass loss and metabolic changes were compared. Results. In the rats of Group I the index of the body mass loss have constituted 16.6% (41.7 gm), and of the Group II -20.6% (53.2 gm). Lowering of indices of mineral and prion metabolism, comparing preoperative values, was observed in both Groups. Dystrophic changes in osseous tissue of vertebral bodies of lumbar vertebral column were noted in animals of both Groups, more pronounced - in Group II. Conclusion. The protein and mineral metabolism disorders may be observed not only in large resection volume, but in exclusion of half and more segment of small bowel from general transit, using gastric shunting, what lacks significant advantages in the extra body mass loss, but leads to more profound metabolic disorders.


2021 ◽  
Vol 29 (5) ◽  
pp. 25-33
Author(s):  
Vadzim Michailovich Vasilkevich ◽  
Ruslan Valerievich Bogdanov ◽  
Ksenia Sergeevna Gilevskaya ◽  
Victoria Igorevna Kulikouskaya

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.


2017 ◽  
Vol 36 (12) ◽  
pp. 1286-1294 ◽  
Author(s):  
J Yu ◽  
H Wu ◽  
Z Lin ◽  
K Su ◽  
J Zhang ◽  
...  

Suberoylanilide hydroxamic acid (SAHA) exerts marked anticancer effects via promotion of apoptosis, cell cycle arrest, and prevention of oncogene expression. In this study, serum metabolomics and artificial intelligence recognition were used to investigate SAHA toxicity. Forty rats (220 ± 20 g) were randomly divided into control and three SAHA groups (low, medium, and high); the experimental groups were treated with 12.3, 24.5, or 49.0 mg kg−1 SAHA once a day via intragastric administration. After 7 days, blood samples from the four groups were collected and analyzed by gas chromatography–mass spectrometry, and pathological changes in the liver were examined using microscopy. The results showed that increased levels of urea, oleic acid, and glutaconic acid were the most significant indicators of toxicity. Octadecanoic acid, pentadecanoic acid, glycerol, propanoic acid, and uric acid levels were lower in the high SAHA group. Microscopic observation revealed no obvious damage to the liver. Based on these data, a support vector machine (SVM) discrimination model was established that recognized the metabolic changes in the three SAHA groups and the control group with 100% accuracy. In conclusion, the main toxicity caused by SAHA was due to excessive metabolism of saturated fatty acids, which could be recognized by an SVM model.


2019 ◽  
Vol 18 (2) ◽  
pp. 114-119
Author(s):  
A. B. Smirnova ◽  
B. S. Pershin ◽  
N. V. Myakova

Modern technologies of treatment of children with oncohaematological diseases allowed to noticebly increase the survival indexes in this group of patients, enhancing the value of maintenance of their life quality. More than half of those who received long-term steriod and radiation treatment develop cataract that causes decrease in vision. In this review we represent data concerning mechanisms of cataract formation in patients after steriod and radiation treatment, results of anatomical, physiological and biochemical studies of the lens as well as metabolic changes in aqueous humor leading to cataract formation.


Author(s):  
R. M. Sachuk ◽  
S. V. Zhyhalyuk ◽  
I. M. Lukyanik ◽  
M. S. Mandyhra ◽  
Ya. S. Stravsky ◽  
...  

The purpose of the work was to determine, in experiments on rodents, the parameters of acute toxicity, allergenic and locally irritative effects of iodine-containing uterine drug for the treatment and prevention of intrauterine infections of animals. Materials and methods. Preclinical studies of acute toxicity of “Yodosol” containing iodine and potassium iodide were performed on 90 white mice, 30 white outbred rats and 6 rabbits. Clinical, pharmacotoxicological and statistical methods were used. Results of work. It has been found that at intragastric administration in experimental rats and mice, DL50 values exceed 8,000 mg/kg body weight and have no effect on the behavioral responses and physiological parameters of laboratory animals. It has been investigated that “Yodosol” aerosol has no local toxic and irritant effects on the skin and mucous membranes of laboratory animals (rabbits). Conclusions. The use of the drug «Yodosol», in doses above 8,000 mg/kg body weight, does not affect the behavioral responses and physiological parameters of laboratory animals. The drug has no local toxic and irritant effects on the skin and mucous membranes. According to the requirements of SOU 85.2-37-736:2011 and GOST 12.1.007-76, the newly developed drug “Yodosol” belongs to low-toxic substances — 4 toxicity classes


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