scholarly journals S-ADEMETHIONINE EFFECT ON THE ACTIVITY OF FREE RADICAL OXIDATION PROCESSES AND ARGININE/CITRULLINE CYCLE WITH DOXORUBICIN-INDUCED LIVER INJURY

Author(s):  
G.S. Maslova ◽  
R.I. Skrypnyk ◽  
І.М. Skrypnyk

Seeking for effective methods for doxorubicin-induced toxicity prevention is of great clinical importance. The aim of the study is to investigate the effect of S-ademethionine on the activity of free radical oxidation and antioxidant protection and arginine / citrulline cycle, and the relationship between the indicators during the modeled doxorubicin-induced liver injury in rats. Materials and methods. The series of study were performed on 30 white non-linear adult rats, 15 (50%) males, 15 (50%) females, weighing 160-220 g. The experimental animals were divided into 3 groups: I group (n=10) included rats (5 males and 5 females), which during 3 days were intraperitoneally administered with doxorubicin of 5 mg/kg/day to achieve cumulative dose of 15 mg/kg and 0.9% sodium chloride solution 1 ml; ІІ group (n=10) included rats (5 males and 5 females), which for 3 days were administered with doxorubicin in dosage similar to that in group I and S-ademethionine intraperitoneally in a dose of 100 mg/kg/day with a total dose of 300 mg/kg; ІІІ group (n=10) included rats (5 males and 5 females), which were injected intraperitoneally for 3 days with 0.9% sodium chloride 1 ml solution by 2 injections. Thiobarbituric acid reactants, arginine, catalase, arginase and ornithine decarboxylase activity were studied in the liver homogenate. Results. The rats of group I in the course of doxorubicin administration demonstrated the growth of the thiobarbituric acid reactants in 2.57 times (p=0.002) in the liver homogenate that was accompanied by 1.7-fold decreased arginase activity compared to the control group III. An inverse correlation was found between the content of thiobarbituric acid reactants and arginase activity in the liver homogenate of group I rats (r=-0.71; p=0.02). Coadministration of S-ademethionine and doxorubicin administration led to 1.4-fold increase in catalase activity in the liver homogenate of rats compared to the control (p=0.009) that reduced the severity of oxidative stress and prevented changes in the arginine/citrulline cycle. Conclusions: S-ademethionine combined with doxorubicin, reduces the activity of free radical oxidation by potentiating the production of antioxidant protective enzymes that prevent impairments in the arginine / citrulline cycle.

Author(s):  
O. V. Lototska

Toxic effects of heavy metals on animals and humans is aggravating the presence of surfactants. The aim of our research was to identify the peculiarities of free radical oxidation and antioxidant protection in the use of drinking water with subtoxic doses of potassium and sodium stearates in combination with copper on the body of warmblooded animals, such as the liver of experimental rats. Analysis of indicators allows asserting that in experimental rats liver homogenate observed activation of free radical oxidation, the intensity of which depended on the concentration of stearates in water. More pronounced changes were in animals that consumed water with potassium stearate.The action of potassium stearate observed inhibition of antioxidant systems while under the influence of sodium stearate – its activation. Changes in performance were more pronounced in combination stearates with copper.


Author(s):  
O. B. Furka ◽  
I. B. Ivanusa ◽  
M. M. Mykhalkiv ◽  
I. M. Klishch

Background. Acetaminophen is a drug used to relieve pain syndrome. It is used both independently and in composition of combined drugs. Type 2 diabetes is an age-related disease that is associated with a violation of insulin synthesis by pancreas.Objective. The aim of the research was to study the effect of acetaminophen on major free radical oxidation indices of rats with type 2 diabetes mellitus in time dynamics.Methods. We conducted two series of experiments. The first series comprised rats with type 2 diabetes mellitus and acute acetaminophen toxic lesions. The second series involved rats with type 2 diabetes mellitus and acetaminophen administration at a dose of 55 mg/kg for the period of 7 days.Results. Administration of acetaminophen for rats with type 2 diabetes mellitus caused the increase in the content of malondialdehyde, diene and triene conjugates and Schiff bases in blood plasma and malondialdehyde, diene and triene conjugates in liver homogenate. The maximum increase in these indices was observed on the first day of the experiment. Gradually these indices decreased on the 3rd, 5th and 7th days of the experiment.Conclusions. Free radical oxidation increased in both series of the experiment. This process developed in rats with type 2 diabetes mellitus and acute acetaminophen toxic lesions more intensively, than in rats with type 2 diabetes mellitus and administration of acetaminophen at the highest therapeutic dose during 7 days.


Author(s):  
AO Vorvul ◽  
II Bobyntsev ◽  
OA Medvedeva ◽  
IuE Azarova ◽  
AE Belykh ◽  
...  

Studying the effects of regulatory peptides on the stress-induced shifts in the bodily processes is of great fundamental and applied significance. Currently, a wide range of peptide neurotropic drugs, affecting the stress response development, are used in medicine, and new promising molecules are being studied. The study was aimed to assess the effects of the adrenocorticotropic hormone (ACTH) synthetic analog, ACTH(6-9)-Pro-Gly-Pro, administered at a dose of 5, 50 and 500 μg/kg, on the free-radical oxidation processes in Wistar rats, subjected to chronic restraint stress (CRS) during two weeks. Serum levels of 8-oxo-2'-deoxyguanosine (8-OHdG) and superoxide dismutase 3 (SOD3) were assessed by enzyme immunoassay, and the levels of thiobarbituric acid reactive substances (TBARS) were assessed by fluorimetric method. CRS lead to the significant increase in the 8-OHdG levels by 18.4% (p = 0.01) and the decrease in the SOD3 levels by 14.3% (p = 0.01), however, it had no effect on the levels of TBARS. ACTH(6-9)-Pro-Gly-Pro, administered at a dose of 5 and 50 μg/kg, significantly decreased the levels of 8-OHdG by 19.8% (p = 0.03) and 30% (p = 0.001), respectively. Thus, it was found that CRS resulted in oxidative stress in animals. ACTH(6-9)-Pro-Gly-Pro administration at a dose of 5 and 50 μg/kg inhibits the stress-induced free-radical oxidation processes.


2015 ◽  
Vol 17 (3) ◽  
Author(s):  
O. Y. Zarichna

<p>In experiments on rats with modulated hypothyroidism, acute galactosamine hepatitis, acute hepatitis combined<br />with merkazolil-induced hypothyroidism the changes in the indices of free-radical oxidation in blood and liver<br />homogenate were studied. Results of the investigation indicate a pronounced increase of lipid peroxidation products,<br />both in blood and in liver homogenate against the backdrop of exhaustion of the enzymatic and non-enzymatic links<br />antioxidant protection system in animals with hypothyroidism. In case of acute galactosamine hepatitis increase of<br />lipid peroxidation products, both in blood and in liver homogenate against the background of activation units both<br />components of the antioxidant protection system was established. The most significant inhibition of the enzymatic<br />and non-enzymatic links antioxidant protection system suffered rats with acute hepatitis on the background of<br />hypothyroidism. It is concluded that failure revealed a mutual gain reflects the negative impact of acute toxic liver<br />injury and thyroid hormone deficiency.</p>


Author(s):  
O. V. Dzhyhaliuk ◽  
H. I. Stepaniuk ◽  
N. V. Zaichko ◽  
S. I. Kovalenko ◽  
K. P. Shabelnyk

According to the literature the leading cause of mortality among the population of Ukraine are cardiovascular diseases, what incidence tripled over the past 25 years and today stands at801.6 in100 000. It necessitates a search for new chemical compounds, suitable for creating manufacturing with a better safety profile and a high degree of efficiency.The aim of the study was to describe the effect of 4-[4-oxo-4N-quinazoline-3- il] benzoic acid (PC-66), compared with kordaron on the processes of free radical oxidation, endothelial nitric oxide production and activity of marker enzymes cytolysis cardiomyocytes adrenaline myocardiodystrophy (AMD) in rats.The study was conducted on 28 nonlinear rats of both sexes (weight – 165–220 grams), divided into four groups: group I (n = 7) – intact rats; group II (n = 7) – rats with untreated AMD (control); group III (n = 7) – rats with AMD treated with entity PC-66 (10 mg/kg intraperitoneally (i/p)); Group IV (n = 7) – rats with AMD treated with kordaron (10 mg/kg, i/p).Research shown that the development of a pilot AMD in rats was characterized by increased free radical oxidation processes, depletion of antioxidant defense system (with decreased content of G-SH, activity of superoxide dismutase and glutathione peroxidase), oppression of endothelial NO production. The most expressive metabolic disturbances were registered in the acute period of AMD (as of 2nd day). The use of 4-[4-oxo-4N-quinazoline-3-il] benzoic acid (PC-66, 10 mg/kg, i/p) provided an expressive cardioprotective effect which was compared with kordaron (10 mg/kg, i/p) at various stages of AMD.The mechanisms of cardioprotective action 4-[4-oxo-4N-quinazoline-3-il] benzoic acid can be realized due to the stabilization of cellular and subcellular membranes (as evidenced by the dynamics of marker enzymes cytolysis cardiomyocytes in serum and reduction of TBA-reactive substances in the myocardium), increasing the efficiency of the antioxidant system and correction of cellular redox buffer (as evidenced by the increasing pool of reduced glutathione, glutathione peroxidase and superoxide dismutase activity increased) and anti-ischemic activity associated with increased activity of endothelial NO synthase in cardiac muscle.


Pharmacia ◽  
2020 ◽  
Vol 67 (4) ◽  
pp. 253-259
Author(s):  
Sergii Shebeko ◽  
Igor Zupanets ◽  
Inna Otrishko

The efficacy of N-acetylglucosamine in rats with chronic kidney disease is described in this article. The results of the study show that N-acetylglucosamine significantly increased (p&lt;0.05) the excretion of nitrogen compounds (creatinine by 100.4% and urea by 46.6%) and as a result de-creased the level of azotemia. The intensity of free radical oxidation was significantly decreased (p&lt;0.05) (blood conjugated dienes by 32.9%, blood thiobarbituric acid reactive substances – by 14.1%, kidney conjugated dienes – by 40.1% and kidney thiobarbituric acid reactive substances – by 26.3%) and the balance of kidney antioxidant system was restored. N-acetylglucosamine was significantly superior (p&lt;0.05) to comparator quercetin in renal excretory function and nitro-gen metabolism by the most of indicators and was not inferior to the influence on the free radical oxidation and kidney oxidative stress. Thus, N-acetylglucosamine is advisable to further experimental studies at i.m. administration as a chronic kidney disease treatment.


2018 ◽  
pp. 9-13
Author(s):  
Yu.I. Silenko ◽  
M.V. Khrebor ◽  
Y.M. Silenko ◽  
O.A. Pisarenko

A number of scientists put forward and confirmed the assumption of the presence in the body of biological regulators, polypeptides, carrying out the transfer of information necessary for the functioning, development and interaction of cell populations. The problem of studying the mechanism of action and clinical application of polypeptides is key in modern medicine. The aim of the research is to examine the clinical parameters and the state of free radical oxidation in blood and periodontal tissues of white rats in the treatment of spontaneous generalized periodontitis with the use of polypeptides. Materials and methods of the research. Experiments were performed on 280 six-month-old of rats Wistar line of both sexes weighing 120-130 g. During the study, the animals were kept under vivarium conditions in individual cells, food and water were not limited. All animals were divided into the following groups: Group I – intact animals (70), Group II – animals with spontaneous periodontitis (70), Group III – animals with spontaneous periodontitis, treated with thymalin polypeptide preparation in a dose of 0.1 mg / kg i / m daily, for 10 days (70), Group ІV – animals with spontaneous paradontitis, treated with parodontylin polypeptide preparation at a dose of 1 mg / kg i / m, daily for 10 days (70). Blood for research in rats was taken against the background of hexenalum anesthesia with a syringe from the heart into a plastic syringe. Subsequently, it was mixed with sodium citrate (3.8% solution) in a ratio of 9:1 and centrifuged at 1500 rpm for 10 min. Periodontal tissues and jaws of animals were taken and examined immediately after euthanasia. For the study, the collection of periodontal tissues (gums with periosteum) was performed in the area of the upper and lower molars, since periodontitis often affects these tissues. Indicators of free radical oxidation were determined in blood and periodontal tissues. Resorption of bone tissue of the alveolar process was evaluated. Results and discussion. In the treatment of experimental spontaneous periodontitis using thymalin on the 7th day of observations, regression of symptoms of the disease in animals was observed. Hyperemia and edema, bleeding gums remitted. Whereas under the influence of thymalin there is a regression of dental symptoms by 3.8 times, under the influence of parodontylin – by 7.2 times. The condition of periodontal tissues in animals improved more significantly on the 20th day of observation, the scale assessment of dental status indicates that in animals, treated with thymalin, it is 1.1, and by parodontylin – 0.3 points per animal. In studying the processes of lipid peroxidation in periodontal tissues, their significant reduction in rats with spontaneous periodontitis after administering parodontylin has been established. We also observed an increase in the activity of antioxidant enzymes. Hence, the activity of SOD was twice as high, catalase – by 1.95 times. Reactions of lipid peroxidation had the same dynamics in the blood of animals after administering periodontal polypeptides and thymalin, as in periodontal tissues. We observed a significant decrease in the level of conjugated dienes, the concentration of the latter reaches the value of indices of intact animals. Similar results were obtained with regard to the level of TBA-active products, accumulation of MDA, spontaneous hemolysis of erythrocytes. Attention is drawn to the fact that parodontylin reduced lipid peroxygenation of blood to a greater extent than thymalin. We also observed increased activity of SOD, and, on the other hand, the concentration of ceruloplasmin decreased by 25.4%. Thus, administering periodontal polypeptides during spontaneous periodontitis leads to a decrease in the responses of lipid peroxidation in periodontal tissues and blood. To a greater extent this effect is characteristic of parodontylin in comparison with thymalin.


2018 ◽  
Vol 3 (4) ◽  
pp. 9-14 ◽  
Author(s):  
I. A. Andrievskaya ◽  
N. A. Ishutina ◽  
O. L. Kutepova

The aim of the study was to assess free radical processes and their effect on oxygenation of hemoglobin in the blood of 18-21 weeks  pregnant women with exacerbation of cytomegalovirus infection. We  examined 40 pregnant women with exacerbation of cytomegalovirus  infection and various levels of specific antibodies (IgM) at 18-21  weeks and 30 pregnant women without cytomegalovirus. The  spectrophotometric method was used to determine the content of oxyhemoglobin, methemoglobin, thiobarbituric acid (TBA)-active  products, superoxide dismutase in blood erythrocytes; thin layer  chromatography – phosphotidylcholine, lysophosphatidylcholine;  gas-liquid chromatography – arachidonic acid. Exacerbation of  cytomegalovirus infection changes the activity of free radical  oxidation processes, the severity of which is determined by the level  of IgM antibodies and is manifested by a decrease in superoxide  dismutase (p = 0.000) and phosphatidylcholine (p = 0.000), an  increase in phospholipase A2 (p = 0.000), lysophosphatidylcholine (p  = 0.000), arachidonic acid (p = 0.000) and TBA-active products  (p = 0.000). Accumulation of superoxide anion radical and products of lipoperoxidation in erythrocytes decreases  oxyhemoglobin (p = 0.000) and increases methemoglobin (p =  0.000). Exacerbation of cytomegalovirus infection at 18-21 weeks is  associated with the enhancement of free radical lipid oxidation and a  deficiency in the antioxidant activity of superoxide dismutase. It  decreases oxygen transport properties and increases phagocytosis  by red blood monocytes; and pregnant women develop further  hemic hypoxia.


2015 ◽  
Vol 96 (5) ◽  
pp. 798-802
Author(s):  
G A Bayburina ◽  
E A Nurgaleeva ◽  
S A Bashkatov ◽  
D Z Shibkova

Aim. To study the association of rat liver and blood free radical oxidation indicators with different resistance to hypoxia on the long run after ischemic damage caused by systemic circulation arrest. Methods. Circulatory arrest lasting for 5 minutes was modeled at ether anesthesia on male white rats which were further allocated to 3 groups according to resistance to hypoxia. The observation period was 35 days. The levels of reduced glutathione, catalase, and products reacting with thiobarbituric acid were determined in liver homogenates, levels of erythrocyte catalase, total antioxidant activity, glutathione peroxidase, glutathione transferase, and products reacting with thiobarbituric acid - in blood. Statistical analysis was performed by parametric statistics, regression and factor analysis. Results. Rats with different resistance to hypoxia initially differed significantly on the number of safety systems functioning indicators levels in liver tissue and blood cells. Total factor analysis of the entire body of empirical data revealed two factors, conventionally called «resistance to hypoxia» and «antioxidant activity of blood». Daily analysis of the figures recorded at 1, 3, 5, 7, 14, 21 and 35 day of the experiment revealed similarities in common and daily factor solutions, demonstrating the objectivity of the revealed patterns, which emphasizes the significant role of free radical oxidation in anoxic conditions pathogenesis. Conclusion. The balance pro- and antioxidant systems activity in the liver and blood is an essential component of the body’s resistance to hypoxia affecting the survival of the animals after systemic circulation arrest. Their level predicts resistance to hypoxia at the recovery period.


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