Detoxification Function Research Articles

Therapeutic strategy for Parkinson's disease: targeting zinc-binding protein in astrocytes

Parkinson's disease (PD) is a progressive neurodegenerative disease with motor symptoms, such as tremor, akinesia/bradykinesia, rigidity and postural instability due to a loss of nigrostriatal dopaminergic neurons; PD patients also exhibit non-motor symptoms, such as hyposmia, orthostatic hypotension and constipation, which precede motor symptoms. Pathologically, Lewy bodies and neurites, which contains α-synuclein, are observed in the central and peripheral nervous system. To date, it is hypothesized that PD pathology appears first in the olfactory bulb and the enteric nervous system, and propagates progressively through the substantia nigra to finally reach the cerebral cortex. Major medications at present are nosotropic treatments to improve motor dysfunction in PD. Therefore, development of disease-modifying drug is required to slow or prevent PD progression. Astrocytes are known to play an important role in the maintenance of the neuronal environment and exert neuroprotective effects by production of antioxidants and neurotrophic factors and clearing toxic molecules. In the previous study, we demonstrated that astrocytes produced antioxidative molecules metallothionein (MT)-1/2 in response to oxidative stress and protected dopaminergic neurons against oxidative stress. MTs are cysteine-rich proteins possessing antioxidative properties. MTs bind to metals such as zinc (Zn) and copper (Cu) and function in metal homeostasis and detoxification; MTs regulate Zn-mediated transcriptional activation of various genes. Recently, it is reported that MTs prevent Cu-induced aggregation of α-synuclein. In this article, we review a new therapeutic strategy of neuroprotection in PD by targeting MTs in astrocytes.

Pathomorphogenesis in goats with Coccidiosis

The problem of the spread of coccidiosis (eimeriosis) in animals is still an urgent problem for veterinary specialists around the world. In this regard, the aim of the study was to study the most complete pathomorphological picture of this disease in goats. The research material was the fallen kids of the Alpine breed. The research was carried out on the basis of one of the goat breeding farms in the Sverdlovsk region. Diagnostics was performed according to clinical, laboratory and pathomorphological studies. Research results. The article describes the morphological picture of pathological changes in the parenchymal and target organs. The scientific novelty lies in the fact that a morphological assessment of changes in target organs, parenchymal organs that provide detoxification function in the body, in the organs of the immune system and in parenchymal organs that perform vital functions in the body of blood circulation and gas exchange has been carried out.

Anti-Aging Physiological Roles of Aryl Hydrocarbon Receptor and Its Dietary Regulators.

The vast majority of the literature on the aryl hydrocarbon receptor is concerned with its functions in xenobiotic detoxification. However, in the course of evolution, this receptor had to have physiological (rather than toxicological) functions. Our aim was to review the aryl hydrocarbon receptor’s role in the physiological functions involved in aging. This study was performed by searching the MEDLINE and Google Academic databases. A total of 34 articles were selected that focused specifically on the aryl hydrocarbon receptor and aging, the aryl hydrocarbon receptor and physiological functions, and the combination of both. This receptor’s main physiological functions (mediated by the modulation of gene expression) were cell regeneration, the immune reaction, intestinal homeostasis, and cell proliferation. Furthermore, it was shown that the loss of this receptor led to premature aging. This process may be caused by the dysregulation of hematopoietic stem cells, loss of glucose and lipid homeostasis, increase in inflammation, and deterioration of the brain. We conclude that the aryl hydrocarbon receptor, apart from its well-established role in xenobiotic detoxication, plays an important role in physiological functions and in the aging process. Modulation of the signaling pathway of this receptor could be a therapeutic target of interest in aging.

Clinical and Immunomorphological Features of Liver Damage in Severe Preeclampsia

Background.Liver diseases associated with pregnancy are recorded in 0.73% of pregnant women, often accompanied by the development of hepatic dysfunction/insufficiency, and are the cause of increased morbidity and mortality in both mother and child. A pathomorphological study helps to understand the pathophysiology of severe liver damage in preeclampsia, and to optimize the management of such patients.Aims to study the clinical, morphological and immunohistochemical features of liver tissue lesions in the most severe forms of preeclampsia and eclampsia, which ended in death.Methods.Autopsy material analysis of 10 patients who died from preeclampsia, eclampsia and their complications (main group) and 3 patients who died from other causes (comparison group). Pathomorphological and immunohistochemical studies of organs and tissues (in particular, liver tissue) were performed using a marker of neurons and neuroendocrine cells -NSE and a marker of endotheliocytes CD-34.Results.An immunohistochemical study with a CD-34 endotheliocyte marker in the main group revealed a vascularization deficiency in the 2nd and 3rd zone of hepatic acini, there were also foci of necrosis. Such changes indicate deep and prolonged hypoperfusion. The use of the NSE marker in the group of patients who died from preeclampsia/eclampsia revealed a sharp increase in Kupffer cells in the first and second zones of acini with pronounced immunoexpression of NSE in the nuclei and cytoplasm of these cells, which indicates severe hepatic dysfunction (in particular, impaired detoxification and elimination functions of the liver). At the same time, only 3 out of 10 women in the main group are clinically registered with HELLP syndrome, while the rest had signs of multiple organ (including acute liver) failure.Conclusions.The clinical symptoms of liver damage, including those with severe preeclampsia, arise, as a rule, already against the background of severe morphological changes in its tissue and, as a rule, indicate functional decompensation. Liver immunology remains little studied, which requires further research on this problem.

Polymorphisms in oxidative stress, metabolic detoxification, and immune function genes, maternal exposure to ambient air pollution, and risk of preterm birth in Taiyuan, China

Exposure to air pollutants may be associated with preterm birth (PB) through oxidative stress, metabolic detoxification, and immune system processes. However, no study has investigated the interactive effects of maternal air pollution and genetic polymorphisms in these pathways on risk of PB. The study included 126 PB and 310 term births. A total of 177 single nucleotide polymorphisms (SNPs) in oxidative stress, immune function, and metabolic detoxification-related genes were examined and analyzed. The China air quality index (AQI) was used as an overall estimation of ambient air pollutants. Among 177 SNPs, four SNPs (GPX4-rs376102, GLRX-rs889224, VEGFA-rs3025039, and IL1A-rs3783550) were found to have significant interactions with AQI on the risk of PB (Pinteraction were 0.001, 0.003, 0.03, and 0.04, respectively). After being stratified by the maternal genotypes in these four SNPs, 1.38 to 1.76 times of the risk of PB were observed as per interquartile range increase in maternal AQI among women who carried the GPX4-rs376102 AC/CC genotypes, the GLRX-rs889224 TT genotype, the VEGFA-rs3025039 CC genotype, or the IL1A-rs3783550 GT/TT genotypes. After adjustment for multiple comparisons, only GPX4-rs376102 and AQI interaction remained statistically significant (false discovery rate (FDR)=0.17). After additional stratification by preeclampsia (PE) status, a strongest association was observed in women who carried the GPX4-rs376102 AC/CC genotypes (OR, 2.26; 95% CI, 1.41–3.65, Pinteraction=0.0002, FDR=0.035) in the PE group. Our study provided the first evidence that association between maternal air pollution and PB risk may be modified by the genetic polymorphisms in oxidative stress and immune function genes. Future large studies are necessary to replicate and confirm the observed associations.

Comparative assessment of biological activity of peloids of Ukraine of different genesis

The article presents the results of comprehensive studies of the influence of peloids from different geographic regions of Ukraine and different genesis on the course of experimental pathology. Methods:At the first stage of research we have determined the type of peloids these are medium-mineralized weakly sulfide magnesium-sodium silt peloids, low-ash organic sapropels, and peat low-mineralized high-ash sulfide-free peloids. Physicochemical parameters have been established: mass fraction of moisture, volumetric weight, hydrogen sulfide content, contamination with particles with a diameter greater than 0.25 × 10-3 m, shear stress, stickiness, specific heat capacity, the content of organic substances, colloidal complex, the concentration of water conduit ions (pH) , redox potential (Eh). In the second stage of the study, 55 white rats were examined for the state of the liverʹs detoxification function (by carrying out a metabolic test using sodium thiopental) and the morphological form of the liver in normal conditions and toxic alcoholic hepatosis. The toxic alcoholic hepatosis model was induced by daily (30 days) intragastric watering of animals with a 25% solution of ethyl alcohol. From the 15th day, the rats received a course of applications: a cake with the corresponding peloids was applied to the bare part of the back. Results: It was determined that the peloids used had a positive effect on animalsʹ condition, which was expressed in the restoration of the detoxification function of the liver and its structural and functional organization. The most substantial positive effect is observed when using silt-sulfide peloids, which, according to the authors, is due to the peculiarities of their physicochemical composition (increased content of magnesium, chlorides, sodium, as well as hydrogen sulfide). Conclusion: Based on the results obtained, it was concluded that the studied peloids meet the criteria for the quality of therapeutic peloids in terms of physicochemical parameters, biological activity, and expands the possibilities of their application in balneology. Keywords: liver, toxic alcoholic hepatosis, rats, peloids,

Interaction of liver arginase and L-arginine-NO system in the processes of detoxification, lipid peroxidation and the formation of the thyroid status in rats with chronic ethanol intoxication

A sufficient number of facts testifying the importance of liver arginase and nitrogen monoxide in the life processes in the normal and pathological conditions have been accumulated to date. The aim of the study was to determine the significance of the relationship and interaction of liver arginase and L-arginine-NO system in the processes of detoxification, lipid peroxidation and the formation of the thyroid status in rats with chronic ethanol intoxication. In rat experiments using the modern physiological, biochemical research methods and a pharmacological approach, it was found that chronic ethanol intoxication leads to a decrease in the liver arginase activity and the triiodothyronine concentration. At the same time, the increase in the level of “average molecules”, NO3 – /NO2 –, the content of lipid peroxidation products in the plasma, as well as the increase in the blood toxicity degree, the activity of alanine amino transferase, aspartate amino transferase and the narcotic sleep duration were observed. Hyperthyroid rats demonstrated the increased liver arginase activity, the processes of detoxification, lipid peroxidation and body temperature while rats with the experimental hypothyroidism showed the opposite results. The liver arginase depression caused by the injection of Nω-hydroxy-nor-L-arginine (Nor-NOHA), or L-valine into the body prevents the body temperature increase and the development of characteristic changes in the detoxification and lipid peroxidation processes acted upon by exogenous triiodothyronine. Under the conditions of the liver arginase inhibition by Nor-NOHA or L-valine, the ethanol action is accompanied by a more significant inhibition of the liver detoxification function and an increase of NO3 – /NO2 – levels in blood plasma. The preliminary injection of an NG-nitro-L-arginine methyl ester inhibitor of NO-synthase into the animal’s body weakensthe toxic ethanol effect on the liver, as well asthe development of characteristic changes in the liver arginase activity, in the processes of detoxification and lipid peroxidation in rats with chronic ethanol intoxication. Apparently, the activity of liver arginase and L-arginine-NO system determines the severity of detoxification, lipid peroxidation processes and the formation of the thyroid status in the conditions of chronic alcoholization, which is important in the ethanol intoxication pathogenesis.

Possible role of ECMO in multiorgan failure and prolonged CPR: Aluminum Phosphide poisoning

Introduction: Aluminum phosphide (ALP) is one of the most common causes of poisoning. Also, it is commonly used to attempt suicide. Extracorporeal Membrane Oxygenation (ECMO) is a therapeutic method that supports the function of the heart and lungs, giving body enough time for detoxification and organ function improvement; therefore, management of the problem using ECMO is critical in these patients and increases the survival chance. Moreover, the impact of COVID-19 on the treatment course during the COVID-19 pandemic and the patients' involvement and contact with the virus is a critical issue with unknown consequences. Case presentation: The patient was an 18-year-old girl who was hospitalized due to the poisoning aluminum phosphate. The ECMO was connected to the patient during CPR. Then, the patient was transported to a specialized healthcare facility. At the time of arrival, the EF (Ejection Fraction) was less than 5%. During the course of poisoning, the patient developed ARDS, fulminant hepatitis, massive gastrointestinal and vaginal bleeding, and septicemia. The ECMO was weaned on day 5 when the EF was reported 55%. In the following, the general and pulmonary conditions of the patient exacerbated when she was suspected of having COVID-19. The necessary therapeutic measures were done and finally, the patient was discharged after 45 days. Conclusion: ECMO is a useful therapeutic procedure in ALP poisoned patients. In case of careful management, it can be used in multiple organ involvement and prolonged PCR. Considering the COVID-19 pandemic, it is very important to notice the chance of COVID-19 infection in ICU during treatment.

Daylight-activated fumigant detoxifying nanofibrous membrane based on thiol-ene click chemistry

Daylight-activated detoxifying nanofibrous membranes (LDNMs) are fabricated by grafting benzophenone-3,3′,4,4′-tetracarboxylic dianhydride (BD) and biological thiols successively on poly(vinyl alcohol-co-ethylene) (EVOH) nanofibrous membrane. Taking the merits of photoactivity of BD, high-reactivity of biological thiols, and high specific surface area and porosity of the nanofibrous membrane, 1,3-dichloropropene (1,3-D) can be efficiently detoxified on the LDNMs under daylight irradiation via a thiol-ene click reaction. The detoxification function of the LDNMs is “switched on” by light irradiation and continues by following a cascade of chemical attacks of thiyl radicals formed during the photoexcitation process. The resultant LDNMs present rapid detoxification rate (i.e., t1/2 =~30 min) and massive detoxification amount (i.e., ~12 mg/g) against 1,3-D vapor under ambient conditions. More importantly, the LDNMs perform a detoxification tailing effect after moving the light-irradiated membrane to a dark environment, thus ensuring the protective function in the absence of sufficient light sources. The detoxification property of the LDNMs in an outdoor environment with sunlight irradiation shows comparable results to the lab-scale outcomes, enabling them to serve as innovative materials for personal protective equipment in practical applications. The successful fabrication of LDNMs may inspire new insights into the design of protective materials providing aggressive protection.

Cloning, purification and biochemical characterization of two glutathione S-transferase isoforms from Rutilus frisii kutum

Glutathione S-transferases are an important multifunctional family of intracellular enzymes that their detoxification function has been reported in fishes since 1970, but no studies have been conducted on Rutilus frisii kutum GSTs yet. In the present study, RkGSTA and RkGSTM encoding genes were cloned and sequenced and their nucleotide sequences were submitted to NCBI GenBank. In order to reduce the expression challenges of recombinant proteins including low solubility, low yield and insufficient purity issues in E. coli, the pKJE7 chaperone plasmid was used to increase the recovery of expressed proteins in the soluble fractions. Best expression clone was selected for purification by Ni-NTA affinity chromatography. The three-dimensional structural models were constructed by I-TASSER. The optimum temperature of purified RkGSTA and RkGSTM was 35 and 30 °C, with optimum activity at pH 9.0 and 8.5, respectively. The thermostability and pH stability results indicated that RkGSTA is more heat-tolerant than RkGSTM though both of them retained more than 80% of their activities at pH 6.5 to 9.0. Overall, this study represents a comprehensive perspective on the structural and biochemical aspects of this enzyme that would be even used in further researches such as drug design studies in order to eliminate toxicant compounds from the body and environment of fishes to protect them against undesired harmful damages.

Different Behavior of the Histidine Residue toward Cadmium and Zinc in a Cadmium-Specific Metallothionein from an Aquatic Fungus.

Metallothioneins (MTs) are a large superfamily of ubiquitous cysteine-rich metalloproteins with main functions in metal ion homeostasis and detoxification. Neclu_MT1 is a metallothionein from the aquatic fungus Heliscus lugdunensis and so far the only known MT that is solely induced by CdII but not by ZnII or copper ions. In addition to eight cysteine residues, Neclu_MT1 also contains a less common single C-terminal histidine residue. To better understand the role of this histidine residue in metal ion binding, for the first time, potentiometric pH titrations are applied, revealing insights into the protonation and metal ion binding processes. Additional studies with absorption and NMR spectroscopy complement the finding that while the histidine residue is not crucial for the overall metal binding capacity, it does serve as a ligand in the ZnII but not in the CdII form of the protein.

Several studies on the problem of management patients with chronic tonsillitis during periods of remission and exacerbation

Increase in the number of acute and chronic diseases is a global trend. On the one hand, the emergence of new types of viruses, their active mutation, an increase in antibiotic-resistant bacterial strains, a high frequency of immunodeficiency and allergic diseases contribute to this. On the other hand is inadequate treatment of inflammatory diseases of the upper respiratory tract, widespread use of systemic antibiotics without indications. The use of bioregulatory medicines with proven efficacy in the complex treatment can reduce the drug load on the body, reduce the bacterial complications and side effects. Traumeel®S joins the physiological course of inflammation and activates pro-resolving mediators, contributes to its faster completion and tissue repair. The efficacy and safety of Traumeel®S has been confirmed in many randomized clinical trials. The drug has proven its value in almost any inflammatory pathology of the upper respiratory tract and ear. The drug Lymphomyosot®, a multicomponent agent with lymphatic drainage action, has proven itself perfectly in the complex therapy of chronic tonsillitis. In November 2019, the Council of Experts of the National Medical Association of Otorhinolaryngologists on the problems of pathology of the lympharyngeal ring was held. It is recommended to use the multicomponent bioregulatory preparation Traumeel®S to correct the inflammatory process, which has shown in studies a modulating effect on inflammatory mediators without suppressing COX-2 (prostaglandins). With exacerbation of chronic tonsillitis and lymphadenitis of nonspecific etiology, it is possible to use the multicomponent preparation Lymphomyosot®, which helps to improve the drainage and detoxification function of the lymphatic system.

Elevated rates of positive selection drive the evolution of pestiferousness in the Colorado potato beetle (Leptinotarsa decemlineata, Say)

Contextualizing evolutionary history and identifying genomic features of an insect that might contribute to its pest status is important in developing early detection and control tactics. In order to understand the evolution of pestiferousness, which we define as the accumulation of traits that contribute to an insect population's success in an agroecosystem, we tested the importance of known genomic properties associated with rapid adaptation in the Colorado potato beetle (CPB), Leptinotarsa decemlineata Say. Within the leaf beetle genus Leptinotarsa, only CPB, and a few populations therein, has risen to pest status on cultivated nightshades, Solanum. Using whole genomes from ten closely related Leptinotarsa species native to the United States, we reconstructed a high-quality species tree and used this phylogenetic framework to assess evolutionary patterns in four genomic features of rapid adaptation: standing genetic variation, gene family expansion and contraction, transposable element abundance and location, and positive selection at protein-coding genes. Throughout approximately 20 million years of history, Leptinotarsa species show little evidence of gene family turnover and transposable element variation. However, there is a clear pattern of CPB experiencing higher rates of positive selection on protein-coding genes. We determine that these rates are associated with greater standing genetic variation due to larger effective population size, which supports the theory that the demographic history contributes to rates of protein evolution. Furthermore, we identify a suite of coding genes under positive selection that are putatively associated with pestiferousness in the Colorado potato beetle lineage. They are involved in the biological processes of xenobiotic detoxification, chemosensation and hormone function.

Expression of four new ferritins from grooved carpet shell clam Ruditapes decussatus challenged with Perkinsus olseni and metals (Cd, Cu and Zn)

Iron has a fundamental role in life and in its biochemical reactions but, when in excess, it can promote the formation of free radicals which can lead to cell death. Therefore, managing the levels of iron is essential to regulate the production of oxidative stress related to iron, and ferritins are one of the main protein families involved in this process. Ferritins are ≈480 kDa multimeric proteins composed by 24 subunits, each with 19−26 kDa, which can accumulate up to 4500 iron atoms. Besides their role in managing iron bioavailability, they have also developed a role in organism immunity and defence present throughout evolution. In this work, we identified and characterized, for the first time, four different ferritin subunits in the clam Ruditapes decussatus, a bivalve commercially and ecologically important along the south Atlantic coast and in the Mediterranean basin, which is a major target of the parasitic protozoa Perkinsus olseni, considered one of the main causes of high levels of clam mortality. Following phylogenetic annotation, the four ferritins subunits identified were subdivided into two cytosolic and two secreted forms. All four subunits maintain the canonical ferritin structure with four main helices α (A–D) and a small helix (E), but the secreted ferritins present an additional helix in their N-terminal region (F), located after the signal peptide and with possible antimicrobial properties. Additionally, we identified in ferritin 4 an extra helix α (G) located between helices B and C. These alpha helix domains revealed high degree of similarity with antimicrobial peptides associated with antibacterial and antifungal activities. Analysis of the expression of these subunits showed that ferritins 1 and 2 are ubiquitously expressed while ferritins 3 and 4 are present mainly in visceral mass. Ferritin 1 lacked a putative functional iron response element (IRE) and appeared to be under a tight regulation. Ferritins 2 and 3 showed a strong response to infection by parasite Perkinsus olseni in contrast to ferritin 4, whose main response was related to exposure to a combination of metals. The synergistic effect between metals and infection promoted a general upregulation of the four ferritins. In conclusion, our results suggest that ferritins, besides their function in iron and metals detoxification, may play a determinant role in clam immune response.

Assessment of the Two-Glutathione S-Transferase Genotypes GSTM1 and GSTT1 Polymorphism Frequencies in Epithelial Ovarian Cancer in Nasiriya Province

The family of glutathione S-transferases (GSTs) is composed of multiple isozymes with significant evidenceof functional polymorphic variation. Glutathione S-transferase GSTM1 and GSTT1 are members of theGST family, is responsible for metabolism of xenobiotics and carcinogens. Allelic variant of GST genepolymorphisms might impair detoxification function and increase the susceptibility to cancer. The nullgenetic polymorphism in the gene encoding GST Class µ, GSTM1 and GSTT1, has been reported to besignificantly elevated in cancer patient. This study aimed to investigate if these polymorphisms are usefulmarkers for predicting ovarian cancer susceptibility. 30 cases of epithelial ovarian cancer and 30 controlswas used to investigate the frequency of GSTT1 and GSTM1 genotypes by using multiplex conventionalPCR protocol. The frequency of GSTM1 null allele was significantly elevated (100%, P = 0.004) comparedwith GSTT1 active allele (13% P = 0.037). GSTT1 null showed no significant effect in prognosis epithelialovarian cancer (17%, P = 0.551). We conclude that the GSTs might affect in both risk to ovarian cancer.

Heat Stress Triggers Differential Protein Accumulation in the Extracellular Matrix of Sorghum Cell Suspension Cultures.

Plants reprogram gene expression as an adaptive response to survive high temperatures. While the identity and functions of intracellular heat stress-responsive proteins have been extensively studied, the heat response of proteins secreted to the extracellular matrix is unknown. Here, we used Sorghum bicolor, a species adapted for growth in hot climates, to investigate the extracellular heat-induced responses. When exposed to 40 °C for 72 h, heat-sensitive Arabidopsis cell suspension cultures died, while ICSB338 sorghum cell cultures survived by activation of a transcriptional response characterized by the induction of HSP70 and HSP90 genes. Quantitative proteomic analysis of proteins recovered from cell culture medium revealed specific heat stress-induced protein accumulation within the sorghum secretome. Of the 265 secreted proteins identified, 31 responded to heat (≥2-fold change), with 84% possessing a predicted signal peptide for targeting to the classical secretory pathway. The differentially accumulated proteins have putative functions in metabolism, detoxification, and protein modifications. A germin (SORBI_3003G427700) was highly heat-inducible at both protein and gene level. Overall, our study reveals new insights into sorghum responses to heat and provides a useful resource of extracellular proteins that could serve as targets for developing thermotolerant crops. Data are available via ProteomeXchange with identifier PXD021536.

Study of the effects of the principle of low-volume infusion therapy

Objective. To study the effects of low-volume infusion therapy on the pathogenetic elimination of endogenous intoxication in a patient with coronary heart disease.
 Materials and methods. The study included 30 patients diagnosed with COVID-19. The age of the patients was 45-65 years. All patients underwent generally accepted clinical laboratory and instrumental examinations. Rheosorbilact 200 ml intravenous was prescribed to all patients for the purpose of low-volume infusion therapy to reduce metabolic disorders, reduce the amount of free radicals and weaken inflammatory reactions, eliminate endogenous intoxication. The drug contains potassium chloride, calcium contains magnesium chloride, sodium lactate, sodium chloride and sorbitol.
 Results and discussion. The drug was positively received by patients during treatment and no side effects were observed. A “mild” effect on the pH of the blood was observed during the determination of Rheosorbilact. In addition, lactate has been shown to have a positive effect on cardiac function, liver and kidney detoxification function. The positive effect of Rheosorbilact on the functional state of the endothelial layer of microvascular vessels should be noted. As is known, the endothelial layer, which determines the motility of the vascular wall, has anti-inflammatory, antiplatelet, antiproliferative activity. Therefore, improvement of endothelial function under the influence of Rheosorbilact has been observed to increase the stability of hemovascular homeostasis and to maintain a stable level of adequate tissue perfusion in the examined patients. The unconditional advantage of the drug is the improvement of hemorrhagic parameters, as well as prophylactic antithrombotic effect. In elderly patients with ischemic heart disease, a 30 % decrease in platelet aggregation activity was observed during the administration of Rheosorbilact in combination with drugs for complex treatment. One of the positive effects of the drug was the improvement of rheological properties and microcirculation of the blood. In particular, a decrease in blood viscosity from 1.35±0.02 to 1.25±0.03 and a 25 % decrease in the erythrocyte aggregation index were observed in elderly patients.
 Conclusions. Thus, according to the results of the presented study, Rheosorbilact can be prescribed for the treatment of endogenous intoxication for small-volume infusion in patients with COVID-19 diagnosed with cardiovascular diseases. A positive effect on the size was observed.

S-ADEMETHIONINE EFFECT ON PATHOGENETIC MECHANISMS OF DOXORUBICIN-INDUCED LIVER INJURY IN RATS WITH NON-ALCOHOLIC STEATOHEPATITIS

Purpose – to investigate the effect of S-ademethionine on changes in prooxidantantioxidant status and arginine/citrulline cycle during doxorubicin-induced liver injury in rats with non-alcoholic steatohepatitis. Material and methods. Studies were performed on 30 white non-linear adult rats, 15 (50%) of them were males, 15 (50%) - females, weighing 160-220 g. Rats were divided into 3 groups: I (n=10) – rats (5 males and 5 females), whom from the 1st till the 63rd day NASH was simulated, then for 3 days (from the 64th till the 66th day) doxorubicin 5 mg/ kg/day was introduced intraperitoneally reaching cumulative dose of 15 mg/kg and 0.9% sodium chloride solution 1 ml; II (n=10) – rats (5 males and 5 females), whom NASH was simulated and doxorubicin was administered similarly to group I and additionally SAMe 100 mg/kg/day intraperitoneally with a total dose of 300 mg/kg; III (n=10) – rats (5 males and 5 females), which constituted a control group. The content of TBA reactants, arginine, citrulline, catalase activity, arginase, ornithine decarboxylase (ODC) were determined in the liver homogenate. Results. Doxorubicin administration in rats with NASH led to increase of TBA-reactants content with a simultaneous decrease in catalase activity, which was accompanied by a reduction in arginase and ODC activity compared with control (p<0.05). The SAMe injection allowed to reduce the manifestations of oxidative stress, potentiated by doxorubicin, as well as to prevent disorders of detoxification and protein-synthetic liver function.

Quantitative immunodetection of metalloprotein II in Perinereis aibuhitensis after heavy metal exposure

The metal detoxification mechanism is essential for the accumulation activity of some polychaetes. In order to investigate the detoxification function of metalloprotein II in polychaete Perinereis aibuhitensis, a recombinant fusion protein of MP II was successfully expressed in vitro and an anti-MP II polyclonal antibody was got. The tissue distribution of MP II in P. aibuhitensis and the protein expression under Cd, Pb and Zn exposure were detected by ELISA with this antibody. The results showed that MP II was higher in the intestine of P. aibuhitensis, followed by the body wall and parapodium. Cd, Zn and Pb exposure can induced MP II expression, but the change trend of MP II under various heavy metal exposure was different. The amount of MP II induced in P. aibuhitensis increased with the rises of Cd concentration, but there is no significant relationship between Zn and Pb concentration and MP II level.

Effects of both Pro- and Synbiotics in Liver Surgery and Transplantation with Special Focus on the Gut-Liver Axis-A Systematic Review and Meta-Analysis.

The gut-liver axis is of upmost importance for the development of infections after surgery. Further bacterial translocation due to surgery-related dysbiosis is associated with limited detoxification function of the liver compromising outcome of surgical therapy. After liver surgery, about 30% of patients develop a bacterial infection, with the risk of bacteremia or even sepsis-associated liver failure and mortality in >40%. The potential benefit of pro-/synbiotics given before surgery is still under debate. Thus, a systematic literature search on trials comparing patients with or without supplementation and outcome after liver resection or transplantation was performed. Our search strategy revealed 12 relevant studies on perioperative administration of pro-/synbiotics in liver surgery. The pro-/synbiotic combinations and concentrations as well as administration timeframes differed between studies. Five studies were performed in liver transplantation and 7 in liver resection. All studies but one reported lower infection rates (pooled RR: 0.46, 95% CI: 0.31–0.67) with pro-/synbiotics. Liver function was assessed after LT/LR in 3 and 5 studies, respectively. Pro-/synbiotics improved function in 1/3 and 2/5 studies, respectively. Concluding, perioperative pro-/synbiotics clearly reduce infection after liver surgery. However, standard protocols with both well-defined probiotic strain preparations and administration timeframes are pending.