Final Products Of Lipid Peroxidation Research Articles

Ferroptosis is involved in Staphylococcus aureus-induced mastitis through autophagy activation by endoplasmic reticulum stress

Cell death caused by severe Staphylococcus aureus (S. aureus) infection is a fatal threat to humans and animals. However, whether ferroptosis, an iron-dependent form of cell death, is involved in S. aureus-induced cell death and its role in S. aureus-induced diseases are unclear. Using a mouse mastitis model and mammary epithelial cells (MMECs), we investigated the role of ferroptosis in the pathogenesis of S. aureus infection. The results revealed that S. aureus-induced ferroptosis in vivo and in vitro as demonstrated by dose-dependent increases in cell death; the level of malondialdehyde (MDA), the final product of lipid peroxidation; and dose-dependent decrease the production of the antioxidant glutathione (GSH). Treatment with typical inhibitors of ferroptosis, including ferrostatin-1 (Fer-1) and deferiprone (DFO), significantly inhibited S. aureus-induced death in MMECs. Mechanistically, treatment with S. aureus activated the protein kinase RNA-like ER kinase (PERK)-eukaryotic initiation factor 2, α subunit (eIF2α)-activating transcription factor 4 (ATF4)-C/EBP homologous protein (CHOP) pathway, which subsequently upregulated autophagy and promoted S. aureus-induced ferroptosis. The activation of autophagy degraded ferritin, resulting in iron dysregulation and ferroptosis. In addition, we found that excessive reactive oxygen species (ROS) production induced ferroptosis and activated endoplasmic reticulum (ER) stress, manifesting as elevated p-PERK-p-eIF2α-ATF4-CHOP pathway protein levels. Collectively, our findings indicate that ferroptosis is involved in S. aureus-induced mastitis via ER stress-mediated autophagy activation, implying a potential strategy for the prevention of S. aureus-associated diseases by targeting ferroptosis. In conclusion, the ROS-ER stress-autophagy axis is involved in regulating S. aureus-induced ferroptosis in MMECs. These findings not only provide a new potential mechanism for mastitis induced by S. aureus but also provide a basis for the treatment of other ferroptotic-related diseases.

Chronic endometritis. Local prooxidant, antioxidant and immunometabolic disorders. An open-label, prospective, randomized study

Aim. To determine local features of lipoperoxidation processes, antioxidant defense, state of matrix metalloproteinases in chronic endometritis. Materials and methods. Eighty women aged 29.33±6.71 (min-max [24–36]) with histologically and immunohistochemically confirmed chronic endometritis and a history of reproductive losses were examined (group 1). The control group consisted of 30 patients without chronic endometritis confirmed by the results of a histochemical study and no history of reproductive losses, suffering from infertility of tubal-peritoneal origin at the age of 30.11±6.9 years (min-max [24–37]; group 2). All 130 patients underwent transvaginal echography of the pelvic organs, and histological and immunohistochemical examination of endometrial samples was performed. The activity of lipid peroxidation factors was analyzed: primary, secondary and final products of lipid peroxidation in heptane and isopropanolol fractions of uterine cavity aspirate, enzymes of the antioxidant system: superoxide dismutase, catalase, glutathione peroxidase, deoxyribonuclease I (DNase), by spectrophotometric method, remodeling factors – matrix metalloproteinases MMP-2, -9 by flow fluorimetry. Results. In patients of group 1, according to transvaginal echography of the pelvic organs, M-echo was 6.29±1.22 mm, in group 2 – 9.10±1.15 mm. In chronic endometritis, disruption of pro-oxidant and activity of antioxidant factors in the endometrium in women with chronic endometritis and a history of reproductive losses. In the heptane fraction of the phenolic extract, the concentration of primary products of lipid peroxidation (diene conjugates) was 12.98% higher than in the control, the content of secondary products of lipid peroxidation (ketodienes) was higher by 15.45%, conjugated trienes by 18.67% higher than the values in the control group, which indicates increased lipid peroxidation of endometrial cell membranes during CE. In the isopropanol phase, the products of lipid peroxidation of phospholipid acyl residues are detected. In the isopropanol fraction of the lipid extract, the amount of diene conjugates was higher, ketodienes by 24.32% and conjugated trienes by 26.14%. An increase in the activity of the enzymes superoxide dismutase by 23.98%, catalase by 14.34%, glutathione peroxidase by 12.39%, and DNase by 2.9 times was recorded compared to the indicators of group 2. Conclusion. Chronic endometritis is accompanied by changes in the system of pro-oxidant and antioxidant factors, the content of tissue remodeling products. The pathogenetic changes underlying oxidative stress in the endometrium may be increased leukocyte infiltration, imbalance of primary, secondary and end products of lipid peroxidation, enzymes superoxide dismutase, catalase, glutathione peroxidase, deoxyribonuclease I (DNase), expression of matrix metalloproteinases-2, -9.

Changes in the oxidative-antioxidant status of blood in freestyle wrestlers under the influence of physical exertion

Purpose of the study: to evaluate the “lipid peroxidation-antioxidant protection” system in freestyle wrestlers under the influence of intense physical activity in order to identify the nature of oxidative processes and the antioxidant status of the athletes’ body.Materials and methods: the study involved athletes — freestyle wrestlers, boys 18–22 years old, with sports qualifications: candidate master of sports or master of sports, regularly involved in freestyle wrestling. The control group consisted of students who did not have a sports category and were not involved in sports activities, comparable in gender, age, weight category with the comparison group. The material for the study was plasma and red blood cells. Blood sampling from athletes was carried out twice, at the end of the preparatory and competitive periods, in the morning, on an empty stomach from the ulnar vein, in accordance with generally accepted requirements. Components of lipid peroxidation and antioxidant defense were determined using spectrophotometric and fluorometric methods.Results: it was found that in athletes after intense physical activity (competitive period), there is a significantly significant decrease in substrates with double bonds by 61 %, primary products by 59 % and intermediate products by 44 %, an increase in the final products of lipid peroxidation by 25 % against the background of inhibition activity of antioxidant protection components: retinol by 40 %, superoxide dismutase by 7 % and reduced glutathione by 11 %.Conclusion: The level of free radical processes increases during physical activity due to the accumulation of oxygen in organs and tissues, and depends on the intensity and duration of the exercise. In the course of the study, it was established that the preparatory and competitive periods, in comparison with the control group, among freestyle wrestlers, depending on the previous level of physical activity, are characterized by activation of lipid peroxidation processes and inhibition of enzymatic and non-enzymatic components of antioxidant protection. The established changes are recommended to be taken into account when conducting comprehensive rehabilitation of athletes, when developing recommendations for improving the training process, as well as when using antioxidant complexes for athletes aimed at restoring various parts of the body’s antioxidant defense.

Endogenous hepatic toxicity and oxidative stress in the complications of gallstones associated with cholestatic jaundice

Introduction. Cholestatic jaundice installed in gallstones is considered a multifactorial pathogenetic process. The correlation of endogenous hepatic intoxication with the reaction of the pro- and antioxidant system, characteristic of various complications of gallstones associated with cholestatic jaundice, remains an undefined subject. Material and methods. The study included the investigation of 105 patients with complicated gallstones and associated cholestatic jaundice, and the control group – 35 patients with uncomplicated gallstones. The age of the patients varied between 51 and 72 years, with an F/M ratio of 3/1. Results. The degree of endotoxemia, assessed at hospitalization by peptides with average mass values, was consistent with the inflammation present in groups 2 and 3, reporting a statistically significant difference compared to the control group [p c/2 < 0.001 (t = 11.1); p c/3 < 0.001 (t = 11.07)]. DAM, as the final product of lipid peroxidation, evaluated at hospitalization, shows double marked values in all groups compared to the control group [p < 0.001 (t = 10.7); (t = 10.9); (t = 16.5)]. The antioxidant activity, assessed at hospitalization, shows a statistically significant decrease in superoxide dismutase values [p < 0.001 (t = 6.4); (t = 4.1); (t = 5.7)], as well as catalase [p < 0.001 (t = 6.7); (t = 5.6); (t = 7.2)] in all groups, by 30-40% compared to the control group. Conclusions. In established cholestatic jaundice, there is an obvious activation of lipoperoxidation processes, contributing to the increase of endogenous intoxication and early suppression of antioxidant activity. There is a direct relationship between the increase in prooxidant activity and the level of endogenous intoxication in all complications of gallstones associated with cholestatic jaundice, but it is more elevated in infectious complications, indicating a need for an early approach.

Clinical course of pro-oxidant processes in brain structures in rats under conditions of experimental hyperthyroxinemia in age-related dynamics

The search for a connection between changes in the indicators of the pro-oxidant system of brain structures and the thyroid gland as a target organ is an urgent issue. The goal is to investigate the features of the pro-oxidant system against the background of experimental hyperthyroxinemia and to evaluate the age-related changes of malondialdehyde and diene conjugates in brain structures. Among Wistar rats (n=50) intact animals ("control", Σ=20) and experimental animals (under simulated hyperthyroxinemia, Σ=30) were selected for observation. The principle of the model of experimental hyperthyroxinemia lies in the addition of levothyroxine in a dosage of 20 μg/day (manufactured by "Berlin-Chemie AG", Germany) in the form of tablets with subsequent grinding at 9 o'clock in the morning with food. On day 14, hyperthyroxinemia in the animals was found, while the thyroxine level in the peripheral blood was >10 μg/dL in the first 48 hours and further, being >25 μg/dL (the results were verified in the laboratory, confirmed by immunoenzymatic method with the participation of the "Humarlander" test system). After functional testing in rats, highly specific parameters (malondialdehyde, diene conjugates) in the cortex, trunk, and hippocampus were further recorded and evaluated. The humane treatment of animals is certified by the local protocol of the meeting of the commission of the Dnipro State Medical University No. 10 dated 21.06.2023, bioethical principles and rules are taken into account during the experimental research. In the presented work, the results of the biochemical method were used to discuss the importance of the pro-oxidant system at the stage of protection against manifestations of stress and anxiety. Functional dependence on the accumulation of intermediate and final products of lipid peroxidation in the structures of the brain during the study of the state of the pro-oxidant system was found; the age-related dynamics of the activity of malondialdehyde and diene conjugates from young to middle-aged rats under conditions of experimental hyperthyroxinemia was observed; age-related changes contribute to a certain depletion of the activity of pro-oxidant compounds in response to stress as a principle of nervous system protection.

Integral assessment of non-specific lipid peroxidation reactions blood in adolescent girls of the Siberian ethnos

BACKGROUND: Integral parameters, in particular, the oxidative stress coefficient are informative and can be used both for evaluation of pathological conditions and compensatory-adaptive reactions of the organism.
 AIM: To investigate an integral coefficient the activity of nonspecific reactions of lipid peroxidation in adolescent girls of the Buryat, Evenki and Tofalar ethnic groups, as compared to the non-indigenous ethnic groups, by applying.
 METHODS: Total 190 adolescent girls (Buryats, Evenki and Tofalar, and nonindigenous population (for example of Russians)) living in the Irkutsk region were the objects of research. The survey was carried out in expeditionary conditions, in the territories of compact residence of ethnic groups. To calculate the integral coefficient (oxidative stress coefficient), spectrophotometry and fluorometry methods we implemented. The individual indicators: primary, secondary, and final products of lipid peroxidation as well as antioxidant defense components were measured.
 RESULTS: According to the obtained data, a lower content of diene conjugates (DC) (p 0.0001), ketodienes and conjugated trienes (KD and СT) (p=0.0003), -tocopherol (p 0.0001) with elevated levels of TBA-active products (p=0.0074) and superoxide dismutase activity (p=0.0008) in the Buryat ethnic girls group relative to similar parameters of girls in the non-ingenious population was observed. Girls of Tofalar ethnic group had higher values of DC (p=0.0009), with reduced values of KD and CT (p=0.0044) compared to the non-indigenous population. There were no differences among girls of the Evenk ethnic group relative to Russians. An integrative analysis of the state of nonspecific lipid peroxidation reactions using the coefficient showed no significant differences between the studied groups.
 CONCLUSION: The conducted study demonstrates certain changes in the lipid peroxidationantioxidant defence system, in the absence of changes in the total indicator among girls representing Siberian ethnic groups and the Russian population living next to them, which can be the basis for subsequent monitoring of their health status.

Antioxidant, Anti-Inflammation and Antiaging Activities of Artocarpus altilis Methanolic Extract on Urban Particulate Matter-Induced HaCaT Keratinocytes Damage.

Particulate matter (PM) is one of the reasons that exacerbate skin diseases. Impaired barrier function is a common symptom in skin diseases, including atopic dermatitis, eczema and psoriasis. Herbal extracts rich in antioxidants are thought to provide excellent pharmacological activities; however, the anti-pollution activity of Artocarpus altilis extract (AAM) has not been investigated yet. The present study demonstrated that 5 μg/mL of AAM was considered to be a safe dose for further experiments without cytotoxicity. Next, we evaluated the anti-pollution activity of AAM through the PM-induced keratinocytes damage cell model. The results showed that AAM could reduce PM-induced overproduction of intracellular ROS and the final product of lipid peroxidation, 4-hydroxynonenal (4HNE). In addition, AAM not only reduced the inflammatory protein expressions, including tumor necrosis factor α (TNFα), TNF receptor 1 (TNFR1) and cyclooxygenase-2 (COX-2), but also balanced the aging protein ratio of matrix metalloproteinase (MMPs) and tissue inhibitors of metalloproteases (TIMPs) through downregulating the phosphorylation of mitogen-activated protein kinase (MAPK) signaling. For skin barrier protection, AAM could repair PM-induced barrier function proteins damage, including filaggrin, loricrin and aquaporin 3 for providing anti-aging bioactivity. In conclusion, AAM has the potential to be developed as an anti-pollution active ingredient for topical skin products to prevent skin oxidation, inflammation and aging, and restore the skin barrier function.

Effect of systemic ozone use on oxidative modification of lipids and proteins in the colon in experimental colitis

Introduction. The processes of free radical oxidation play a significant role in the pathogenesis of inflammatory bowel diseases. The aim of the work was to study the clinical status, the content of lipid peroxidation products, oxidative modification of proteins in the lesion of the colon in oxazole-induced colitis (OIC) under conditions of intraperitoneal application of ozone. Materials and methods. Wistar rats were modeled for OIC using oxazolone solution. Ozone-oxygen mixture (OX) was injected intraperitoneally once a day for six days. The clinic was assessed by disease activity index (DAI), the content of products of lipid peroxidation (LPO) and oxidative modification of proteins (OMB) was determined in colonic homogenate. Results. Under OIK DAI increases, the level of primary and secondary products in the heptane phase increases in the colonic homogenate; the level of secondary products and end products increased in the isopropanol phase. Under conditions of intraperitoneal application of ozone, DAI decreased, the level of isopropanol-soluble primary, secondary, final LPO products increased in colon homogenate on the 2nd day, the level of heptane- and isopropanol-soluble primary, secondary, final LPO products decreased on the 6th day, early and late LPO products decreased on the 4th, 6th day. We found a moderate and significant relationship on the Cheddock scale between DAI and the content of LPO and OMB products in the colonic homogenate mainly on day 6 of OIC under conditions of intraperitoneal application of ozone. Discussion. The increased content of LPO and OMB products in the lesion of the colon after the use of ozone is probably due to its mediated action (through the activation of ROS) and its ability to act as an oxidant of lipids and proteins of the cells of the mucosa of the colon. Conclusions. The positive effects of intraperitoneal application of ozone in OIC are the basis for further research in studying the mechanism of the protective effect of ozone with the possibility of further application in clinical conditions in inflammatory bowel diseases.

ВЛИЯНИЕ ИНВАЗИВНОГО ВИДА UNIONICOLA YPSILOPHORA (BONZ, 1783) НА МОРФО- И ИММУНОФИЗИОЛОГИЧЕСКИЕ ПОКАЗАТЕЛИ МОЛЛЮСКА ANODONTA CYGNEA (L.) РЫБИНСКОГО ВОДОХРАНИЛИЩА

The effect of the invasive biological species of the Rybinsk Reservoir, the water mite Unionicola ypsilophora (Bonz, 1783) on the morphological and immunophysiological parameters of the infected bivalve mollusks Anodonta cygnea (L., 1758), was studied. The dependence of mollusk infection by water mite on the age, size, fatness coefficient, somatic indices of gills, legs, the content of immune complexes and malondialdehyde, one of the final products of lipid peroxidation, is shown. Indicators of size, total weight, content of immune complexes and malondialdehyde in infected individuals aged 7–10 years significantly exceeded those of uninfected young children 4-5 years old. It is concluded that with age, the level of innate mechanisms of the anti-acaricidal immunity of A. cygnea to water mite decreases, which leads to mass infection and death of older age groups of mollusks. The obtained data can be used to predict the propagation rate of biological invasion of U. ypsilophora in water bodies.

Prospective study of the cytokine profile and antioxidant status of patients with pyoderma

Background. The importance of studying the pathogenetic features of pyoderma associated with Streptococcus pyogenes is associated with the severity of the course of the disease, frequent relapses with a short inter-relapse period, and long-term disability.The severity of the course, long-term disability, violations of the pro-oxidate mechanisms recorded in patients with poidermias associated with Streptococcus pyogenes are priority and timely.
 Aims. Study of the cytokine, prooxidant and antioxidant profiles of patients with pyoderma associated with Streptococcus pyogenes.
 Мethods. А prospective study of the cytokine profile, the level of antioxidant defense enzymes, and lipid peroxidation factors in patients with pyoderma, lasting more than 2 years, associated with Streptococcus pyogenes, was carried out. The study included 100 people with diffuse lesions of smooth skin, identified on the skin surface of Streptococcus pyogenes, at the age of 28.76 6.24 years; in blood serum, the content of cytokines IL-2, IL-8, IL-10, TNF-, IFN-, IL-1 was studied by enzyme immunoassay, in whole blood the content of primary, secondary and final products of lipid peroxidation, antioxidant enzymes protection superoxide dismutase and catalase.
 Results. Analysis of the content of cytokines showed a significant decrease in the concentration of IL-2, an increase in IL-10, TNF-, IL-8, IL-1 in the blood serum of patients with streptoderma compared with the reference values of healthy people (p 0.05). In whole blood plasma, an increase in the concentration of primary, secondary and final products of lipid peroxidation was registered with a significant decrease in the activity of antioxidant enzymes of superoxide dismutase and catalase relative to the indicators of healthy volunteers (p 0.05).
 Conclusions. In patients with streptoderma, an increase in the production of cytokines with pro-inflammatory and chemotactic properties in response to the invasion of the pathogen and its persistence was revealed. The intracellular nature of the parasitization of Streptococcus pyogenes contributes to the enhancement of the systemic and local inflammatory process, the formation of oxidative stress, the accumulation of primary, secondary and final products of lipid peroxidation, and a decrease in the activity of antioxidant enzymes. A decrease in the content of interleukin 2, which has immunoregulatory properties in patients with streptoderma, leads to impaired immune homeostasis, a decrease in the processes of differentiation in the direction of the Th1 immune response, proliferation of T-lymphocytes, a violation of the qualitative and quantitative composition of the main subpopulations of peripheral blood lymphocytes, which is clinically expressed in this occurrence of relapses in categories of patients.

INTENSITY OF LIPID PEROXIDATION IN THE MICROSOMAL FRACTION OF RAT LIVER UNDER THE EFFECTS OF SODIUM BENZOATE AND ASCORBIC ACID

The effect of food preservatives on the state of free radical processes in rat liver cells are studied in the paper. The changes of lipid peroxidation (LPO) products (the level of primary products – diene conjugates (DK), secondary products – ketodienes and conjugated trienes (KD + CT), TBA-active products and final products – Schiff bases) in the microsomal fraction of rat liver were studied under conditions of introduction into the body of sodium benzoate and ascorbic acid. Animals were divided into four groups: group I – intact animals (control); group II – rats, which were administra-tion of ascorbic acid; group III – rats, which were administration of sodium benzoate; group IV – rats, which were administration of sodium benzoate 30 min before the introduction of ascorbic acid. Sodium benzoate and ascorbic acid were administered per os daily for 21 days. Euthanasia of animals was performed under light ether anesthesia on the 21st day after the administration of sodium benzoate and ascorbic acid. It was established that the daily introduction of sodium benzoate into the body leads to the initiation of LPO in the microsomal fraction of the liver, which is evidenced by an increase in the levels of primary, secondary and final prod-ucts of LPO compared to the indicators of intact animals. Sodium benzoate exhibits a higher pro-oxidant effect when combined with ascorbic acid. It has been shown that under the conditions of administration of sodium benzoate and ascorbic acid, LPO processes are intensified, as the levels of DK, KD + ST, TBK-active products and Schiff bases significantly exceed the indicators of the group of ani-mals that were administered only sodium benzoate.

INTENSITY OF FREE RADICAL PROCESSES IN THE POSTNUCLEAR FRACTION OF RAT KIDNEYS UNDER INFLUENCE OF LASER IRRADIATION AND ω-3 POLYUNSATURATED FATTY ACIDS

Introduction. The effect of laser irradiation on the body can lead to local tissue damage, which will be accompanied by changes in biochemical processes that occur in the kidneys. The direction of these changes is completely unclear, so the study of free radical oxidation of lipids and proteins as the main markers of oxidative stress in the body and their correction by ω-3 polyunsaturated fatty acids (PUFA) remains relevant. Aim. To evaluate the intensity of lipid peroxidation and oxidative modification of proteins in the postnuclear fraction of rat kidneys under the action of laser irradiation and additional administration of ω-3 PUFA. Methods. The studies used white outbred rats, which were irradiated daily for 4 minutes with a laser diode with a wavelength of 650 nm, power of 50 mW in the abdominal cavity at a distance of 10 cm from the skin surface. The state of lipid peroxidation (LPO) was determined by the level of primary, secondary and final products. The intensity of oxidative modification of proteins (OMP) was evaluated by the level of carbonyl derivatives and protein SH-groups. To correct the prooxidant state, the animals were additionally injected with ω-3 PUFA. Results. Low-intensity laser irradiation has a destructive effect on the cell membranes of the kidneys, which is expressed by an increase in primary, secondary and final products of LPO in phospholipid extracts and an increase in the intensity of OMP. The introduction of ω-3 PUFAs reduces free radical processes in the kidneys of irradiated rats, but this effect depends on the scheme of their introduction. ω-3 PUFAs do not show antioxidant effect under the conditions of their introduction after laser irradiation. Daily administration of ω-3 PUFA two hours before irradiation shows a slight antioxidant effect only in the initial stages of irradiation. Preliminary seven-day administration of ω-3 PUFA before laser irradiation is the most effective, as it helps to reduce free radical processes. Conclusion. It is established that ω-3 PUFAs are able to have a corrective effect on the action of low-intensity laser irradiation, which depends on the scheme of their introduction. The highest antioxidant effect is observed in groups of animals to which ω-3 PUFA was previously administered before the action of laser irradiation.

The level of products of lipid peroxidation in the blood of piglets at the action feed additive “Sylimevit”

Intensive pig breeding has been reported in the literature to suggest that early weaning of piglets from sows is an extreme stimulus that reduces the protective and adaptive responses of piglets. That is why the aim of the study was to study the effect of the feed additive “Sylimevit” on the level of lipid peroxidation products of piglets after weaning. Two groups of piglets were formed – control and experimental in the amount of 10 individuals in each group, selected on the principle of analogs – age, breed and body weight. During the weaning period, the piglets were kept under the sow in special machines, had constant access to the mother, and from the age of 5 days – free access to concentrated feed. While feeding of animals was carried out in accordance with the norms for a given age of pigs. Prior to the study, a clinical and physiological examination of the piglets was performed. Their general condition and activity when eating food were taken into account. On the 28th day of life, the piglets were weaned from the sow and regrouped from different nests in order to be further maintained during the period of fattening and rearing with a change in the structure of the diet, which served as technological stress for the animals. From the age of 5 days, piglets of all groups were fed pre-starter feed. Piglets of the experimental group, from 21 to 40 days of age, were additionally fed the feed supplement “Sylimevit” at a dose of 100 mg/kg body weight per day. The technological stress of weaning piglets from sows is accompanied by a gradual probable intensification of lipid peroxidation processes. Feeding Sylimevit feed to piglets after weaning helped to reduce the content of intermediate and final products of lipid peroxidation: lipid hydroperoxides – by 52 % (P < 0.001) and TBA-active products – by 22.5 % (P < 0.01). Thus, feeding the piglets of the experimental group of the feed additive “Sylimevit” helped to suppress the processes of lipid peroxidation in animals. Thus, the results of the use of feed additive “Sylimevit” in weaned piglets showed a pronounced antioxidant effect. The components of the feed additive directly interacted with reactive oxygen species and free radicals, preventing the development of oxidative stress.

Autonomous regulation of antioxidant protection and protein exchange in chickens

The tone of the autonomic nervous system, protein metabolism and the activity of the antioxidant system in Cobb-500 cross chickens aged 35 and 60 days were researched. The experiment involved 24 chickens, 8 in each group. In birds, the tone of the autonomic nervous system was determined by the method of variation pulsometry by recording the influence of the sympathetic and parasympathetic systems on the heart rate in chickens. The effect was determined by counting one hundred consecutive cardio intervals and the time interval between each cardiocycle. Venous blood samples were taken from each individual at the age of 35 and 60 days to determine protein metabolism (total protein, albumin, globulins), enzymatic and non-enzymatic links of the antioxidant system and lipid peroxidation depending on the tone of the autonomic nervous system. It was found that the antioxidant level in chickens with a predominance of the sympathetic division prevailed in all other groups regardless of the age of the bird. At 35 days of age, plasma concentrations of diene conjugates were significantly higher in normatonics and vagotonics (P ˂ 0.05). There was a higher level of activity of ketodienes and Schiff bases in chickens with a predominance of the sympathetic division of autonomic nervous regulation compared with normotonics and vagotonics (P ˂ 0.01). The content of total protein, albumin and globulins prevailed in normotonic hens and was the lowest in vagotonic hens at the age of 35 days. The two-month-old bird with a dominant parasympathetic division of the autonomic nervous system and normotonic hens had the highest levels of total protein, globulins, and conversely, sympathicotonic hens outnumbered the latter in albumin levels. Histidine content was highest in chickens with a balanced type of autonomic nervous system compared to sympathicotonics and vagotonics (P ˂ 0.05). The concentration of sulfur-containing amino acid methionine was highest in vagotonic chickens (P < 0.05) compared with sympathicotonics. Threonine was highest in sympathicotonics compared with other groups of animals and significantly outweighed vagotonics (P < 0.05). The level of lipid peroxidation products in 60-day-old sympathicotonic chickens was consistently higher in contrast to normotonics and vagotonics. At the same time there was the smallest increase in the activity of diene conjugates and ketodienes (P < 0.05) in chickens with a dominant sympathetic division of the autonomic nervous system, which indicates a slowdown in the accumulation of the final products of lipid peroxidation. It was found that the predominance of sympathetic tone is characterized by low activity of enzymes of the antioxidant system and tocopherol (P < 0.001, P < 0.01) at 35 and 60 days of age. Indicators of the activity of the antioxidant system had the highest level in vagotonic chickens of the studied age period (P < 0.05, P < 0.01, P < 0.001). The relationship between catalase and tocopherol levels in vagotonic chickens at 35 days of age, which increases at 60 days of age r = 0.53 (P < 0.01) was found.

Hybrid organotin compounds — modulators of apoptotic processes in the liver when administered once and repeatedly to Wistar rats

Introduction. The aim of the study was to evaluate the effect of hybrid organotin compounds bis(3,5–di– tert–butyl–4–hydroxyphenylthiolate) dimethylol (Me3) and ((3,5–di–tert–butyl–4–hydroxyphenylthiolate) triphenylolol (Me5) on the level of markers of oxidative stress and apoptotic processes in the mitochondria during acute and subchronic intragastric administration to Wistar rats (females) in the maximum tolerated dose. Materials and methods. The objects of study were hybrid organotin compounds, the administration was carried out at the maximum tolerated dose of 2000 mg/kg (Me3) and 750 mg/kg (Me5) with a single and multiple intragastric administration. The study was conducted on 60 Wistar rats (females) weighing 190-210g. The concentration of cytochrome C (ng / g protein), caspase-9(ng / g protein), 8-hydroxy-2' — deoxyguanosine (8-OHdG) (ng/g protein), malondialdehyde (MDA) (nM / g protein)was determined in mitochondrial liver samples using test systems by enzyme immunoassay; by the biochemical method-the amount of protein (mg / ml) — by the biuretic method. Results. Me3 in both series of the experiment showed itself as a more pronounced antioxidant than Me5, which did not show its antioxidant properties. In group I animals, there were no statistically significant differences in the level of MDA and Cit C in relation to the control group, no mitDNA damage was detected, but K9 activity increased by 17%. With the introduction of Me5, the value of the MDA indicator increased by 55.5%, 8 — OHdG by 12.4% and Cit C by 66.2%. In group IV, the amount of MDA as the final product of lipid peroxidation (POL) increased by 13.6%, in group V by 22.5%. With the introduction of Me3, the level of Cit C was reduced by 23.5%, with the introduction of Me5, on the contrary, it was slightly increased. K9 activity was reduced in both experimental groups, by 9.6% and 17.3%, respectively. Discussion. Hybrid OOS containing a fragment of 2,6-di-tert-butylphenol have a dual structure. The tin-containing component is prooxidant, and the radical of the spatially hindered phenol, on the contrary, is antioxidant. It is the different ratio of the described fragments in the molecules of the substances under study, in our opinion, that led to the appearance of different degrees of influence on the metabolism of mitochondria. Conclusion. Both substances that modulate changes in oxidative stress and the activity of apoptotic processes are recommended for further research as antitumor medicinal agents.

Effectiveness of oxidative stress correction at non-alcoholic steatohepatitis and diabetic kidney disease in patients with type 2 diabetes mellitus

Objective — to study the state of oxidative‑antioxidant homeostasis, intensity of hepatocytes’ apoptosis based on the blood levels of cytokeratin‑18 in patients with non‑alcoholic steatohepatitis (NASH) and type 2 diabetes mellitus (DM 2) depending on the stage of diabetic kidney disease, and to investigate effects of the medications’ complex on the above factors.
 Materials and methods. The investigation was performed in the dynamics of treatment of 75 NASH patients with DM 2 and DKD of stage I — III. Depending on the treatment type, patients were divided into two groups. The control group (37 patients) was administered a hypocaloric diet with account of dietary restrictions #9, received essential phospholipids (Essentiale forte H) 300 mg 2 caps. 3 times a day) during 30 days for the NASH treatment, and antidiabetic and lipid‑lowering therapy with metformin hydrochloride (Metformin ‑Teva) 1000 mg per day, rosuvastatin (5 mg 1 time per day) for 1 month. The main group consisted of 38 patients and in addition to the similar 30 days of dietary recommendations, essential phospholipids, hypoglycemic and hypolipidemic therapy, received quercetin and povidone (Corvitin) 500 mg intravenously in 100 ml of isotonic sodium 10 mg for 10 days. The mean age of patients was (54.7 ± 3.56) years. Both groups were randomized by age, gender ratio and disease duration.
 Results. Before the treatment, the significant degree of oxidative stress was established, which was accompanied by accumulation in the blood of intermediate and final products of lipid peroxidation and oxidative modification of proteins. Blood plasma levels of malonic aldehyde exceeded the reference values in 2.1 times (p < 0.05). The state of the antioxidant defense system was significantly disbalanced. The blood levels of reduced glutathione were in 1.7 times lower than in healthy individuals (p < 0.05), glutathione peroxidase activity was inhibited in 1.3 times (p < 0.05), which explains the high intensity of oxidative stress in the examined patients.
 Conclusions. In patients with type 2 diabetes mellitus, accompanied by diabetic kidney disease with comorbid non‑alcoholic steatohepatitis, the significant increase in the oxidative stress intensity was observed, together with 1 to 3‑fold raise (p < 0.05) in the blood levels of intermediate and final products of lipid peroxidation and oxidative proteins’ modification.

Indicators of protein metabolism and intensity of lipid peroxide oxidation in chickens with different vegetative status

The tone of the autonomic nervous system, protein metabolism and enzymes in Cobb-500 crossbred chickens aged 35 and 60 days were studied. The experiment involved 24 chickens, 8 in each group. In birds, the tone of the autonomic nervous system was determined by the method of variation pulsometry. The essence of the method is to record the effect of sympathetic and parasympathetic systems on heart rate in chickens. The effect was determined by recording one hundred consecutive cardio intervals and counting the time interval between each cardiocycle. Venous blood samples were taken from each individual at the age of 35 and 60 days to determine the indicators of protein metabolism (total protein, albumin, globulins) and lipid peroxidation depending on the tone of the autonomic nervous system. It was found that the antioxidant level in chickens with a predominance of the sympathetic division prevailed in all other groups regardless of the age of the bird. At 35 days of age, plasma concentrations of diene conjugates were significantly higher in normatonics and vagotonics (P ˂ 0.05). There was a higher level of activity of ketodienes and Schiff bases in chickens with a predominance of the sympathetic division of autonomic nervous regulation compared with normotonics and vagotonics (P ˂ 0.01). The content of total protein, albumin and globulins prevailed in normotonic hens and was the lowest in vagotonic hens at the age of 35 days. The two-month-old bird with a dominant parasympathetic division of the autonomic nervous system and normotonic hens had the highest levels of total protein, globulins, and conversely, sympathicotonic hens outnumbered the latter in albumin levels. Histidine content was highest in chickens with a balanced type of autonomic nervous system compared to sympathicotonics and vagotonics (P ˂ 0.05). The concentration of sulfur-containing amino acid methionine was highest in vagotonic chickens (P < 0.05) compared with sympathicotonics. Threonine was highest in sympathicotonics compared with other groups of animals and significantly outweighed vagotonics (P < 0.05). The level of lipid peroxidation products in 60-day-old sympathicotonic chickens was consistently higher in contrast to normotonics and vagotonics. At the same time there was the smallest increase in the activity of diene conjugates and ketodienes (P < 0.05) in chickens with a dominant sympathetic division of the autonomic nervous system, which indicates a slowdown in the accumulation of the final products of lipid peroxidation.

The Changes of Prooxidant-Antioxidant and Energy Homeostasis in Rates with Impaired Glucose Tolerance

Topicality.Violation of glucose utilization leads to disruption of all types of metabolic processes. Particularly dangerous in the prognostic aspect is the combination of carbohydrate metabolism disorders and other endocrine pathologies, in particular hypothyroid dysfunction.
 The objective of the study was to examine prooxidant-antioxidant changes ofblood serum, teeth pulp and oral mucosa in rats with impaired glucose tolerance on the background of iodine deficiency.
 Materials and Methods. The studies were carried on 60 female rats, which were divided into two research groups - rats with impaired glucose tolerance and insulin resistance on the background of iodine deficiency. Lipid peroxidation processes were evaluated due to the content of diene conjugates and active products that react with thiobarbituric acid in blood serum, teeth pulp and oral mucosa. Antioxidant defence of blood serum was characterized by catalase, ceruloplasmin, superoxide dismutase, glutathione peroxidase, glutathione reductase activity and iron transferrin saturation. Energy metabolism was examined by the activity of succinate dehydrogenase, malate dehydrogenase and lactate dehydrogenase in blood serum.
 Results.Impaired glucose tolerance was foundto lead to the activation of lipoperoxidation, mainly due to the accumulation of final products of lipid peroxidation in all studied tissues against the background of redistribution of the activity of antiradical enzymes. Under these experimental conditions, different changes in the activity of energy synthesis enzymes were observed. The development of combined endocrine pathology has led to more pronounced changes in the prooxidant-antioxidant system and significant suppression of serum dehydrogenase activity.
 Conclusions.The development of insulin resistance on the background of iodine deficiency causes the activation of oxygen-dependent processes in periodontal tissues against the background of reduced antiradical defence and disruption of energy synthesis system.

Amantadine prevented hypersensitivity and decreased oxidative stress by NMDA receptor antagonism after spinal cord injury in rats.

Neuropathic pain (NP) after spinal cord injury (SCI) is a disabling condition, without an effective treatment. Hyperexcitability of N-methyl-D-aspartate (NMDA) receptors and oxidative stress have been reported to be associated with pain development. Amantadine, an NMDA receptor antagonist, has been proposed as a potential therapy for NP. However, its use has not been tested for NP after SCI. To produce SCI, 120 female Wistar rats were used, a contusion injury to the T10 and T12 thoracic vertebrae was performed from heights of 6.25mm and 12.5mm. Nociceptive behaviour, was evaluated with the use of von Frey filaments for 31days. The final products of lipid peroxidation (LP) and concentration of reduced glutathione (GSH) in the injured tissue were quantified by fluorescence spectrophotometry. The antinociceptive effect of the acute (15days after the injury) and chronic (once daily for three days immediately after the injury) with amantadine (6.25-50mg/Kg. I.p.) was determined. Finally, the LP and GSH were quantified in the injured tissue. Acute treatment with amantadine reduced nociceptive behaviour. Concomitantly, LP was decreased by Amantadine treatment while GSH increased in the injured tissue. Similar effects were observed with chronic treatment with amantadine. Data from this study suggested that the antinociceptive effects of amantadine treatment are modulated through oxidative stress and excitotoxicity reduction associated with N-methyl-D-aspartate receptors activation. This study suggests that acute treatment with amantadine decreases hypersensitivity threshold and frequency of hypersensitivity response in a dose-dependent manner, in rats with SCI, by decreasing oxidative stress. Since amantadine is an easily accessible drug and has fewer adverse effects than current treatments for hypersensitivity threshold and frequency of hypersensitivity response, amantadine could represent a safe and effective therapy for the treatment of neuropathic pain. However, further research is required to provide evidence of the effectiveness and feasibility.

Manifestation of oxidative stress during pregnancy in women with chronic diseases of hepatobiliary system against the background of reproductive losses

In the early stages of gestation the changes in the lipid peroxidation can lead to violations of regulatory and protective functions of biomembranes in pregnant women. The objective: to study the changes in the concentration of intermediate and final products of LPO during the first trimester of gestation in patients with early miscarriage against the background of chronic diseases of the hepatobiliary system. Materials and methods. 118 pregnant women in the first trimester of gestation (7-10 weeks), aged 22 - 39 y. o. (mean age 29.4 ± 2.7 years) have been examined.64 women (54.2%) were diagnosed with a risk of miscarriage, and 17 patients were diagnosed with involuntary miscarriage within 10-12 days. All women were diagnosed with non-viral and non-alcoholic chronic HBS paathology: hepatic steatosis had 38 patients (32.2%), 80 patients (67.8%) had non-alcoholic steatohepatitis; in 97 patients (82.2%) chronic non-calculous cholecystitis was diagnosed. The state of lipid peroxidation was assessed by the content of malonic dialdehyde spectrophotometrically, as well as diene conjugates in the blood The indicator of erythrocyte peroxide hemolysis was examined by the level of erythrocyte peroxide resistance. Results. A significant increase in intermediate and final products of lipid peroxidation in pregnant women with an unfavorable premorbid background in the form of chronic diseases of the hepatobiliary system and a history of reproductive losses. A significant increase of MDA and DC concentration was found at the risk of premature termination of pregnancy. The degree of PLO processes activation makes these parameters integrative criteria for the detection of systemic metabolic disorders during gestation in women with GBS extragenital pathology. Conclusion. During physiological pregnancy there is an accumulation of metabolites of lipid peroxidation, which is associated with an increase in basic metabolism in women and an increase in oxygen consumption from the blood.