Lipid Peroxidation System Research Articles

Targeting oxidative stress, iron overload and ferroptosis in bone-degenerative conditions

Abstract Introduction Bone-degenerative conditions, including osteoporosis, rheumatoid arthritis, and osteoarthritis, are major public health concerns worldwide, associated with oxidative stress and iron overload that disrupts bone homeostasis. Ferroptosis, an iron-mediated form of cell death, has emerged as a critical factor in bone degeneration, necessitating a comprehensive review of its role in these conditions. Content This review comprehensively examined the latest research on oxidative stress, iron metabolism, and ferroptosis related to bone biology and degeneration, focusing on their interconnections and potential therapeutic implications. The review revealed that oxidative stress affects various bone cell types, including osteoclasts, osteoblasts, and chondrocytes, contributing to bone loss and cartilage degradation. Iron homeostasis was found to be crucial for bone cell function, with both iron overload and deficiency potentially leading to pathological conditions. Ferroptosis regulation involves a complex interplay between iron metabolism, lipid peroxidation, and antioxidant systems, including the SLC7A11-GSH-GPX4 network and the FSP1-CoQ10H2 pathway. Different bone cell lineages, including mesenchymal stem cells, osteoblasts, osteoclasts, and chondrocytes, exhibit varied responses to ferroptosis induction and regulation. Summary Understanding the molecular mechanisms underlying ferroptosis regulation in bone cells offers promising avenues for developing targeted therapies for bone-degenerative conditions. Outlook Future research should focus on elucidating the specific roles of ferroptosis in different bone disorders and exploring potential therapeutic interventions targeting oxidative stress, iron overload, and ferroptosis pathways to improve the management of these debilitating conditions.

Ferroptosis in schizophrenia: Mechanisms and therapeutic potentials (Review).

Schizophrenia, a complex psychiatric disorder, presents with multifaceted symptoms and important challenges in treatment, primarily due to its pathophysiological complexity, which involves oxidative stress and aberrant iron metabolism. Recent insights into ferroptosis, a unique form of iron‑dependent cell death characterized by lipid peroxidation and antioxidant system failures, open new avenues for understanding the neurobiological foundation of schizophrenia. The present review explores the interplay between ferroptosis and schizophrenia, emphasizing the potential contributions of disrupted iron homeostasis and oxidative mechanisms to the pathology and progression of this disease. The emerging evidence linking ferroptosis with the oxidative stress observed in schizophrenia provides a compelling narrative for re‑evaluating current therapeutic strategies and exploring novel interventions targeting these molecular pathways, such as the glutathione peroxidase 4 pathway and the ferroptosis suppressor protein 1 pathway. By integrating recent advances in ferroptosis research, the current review highlights innovative therapeutic potentials, including N‑acetylcysteine, selenium, omega‑3 fatty acids and iron chelation therapy, which could address the limitations of existing treatments and improve clinical outcomes for individuals with schizophrenia.

Dynamics of Free Radical Oxidative Processes During the Latent Period of Experimental Metastasizing to the Liver

Purpose — to investigate the dynamics of the content of antioxidant enzymes superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPO1), glutathione reductase (GR) and lipid peroxidation products diene conjugates (DC), malondialdehyde (MDA) in the spleen and liver during the latent period of growth and metastasis of experimental tumor.Materials and methods. Using 28 white male rats, a model of hematogenous liver metastasis was created by transplanting sarcoma 45 cells (S45) into the spleen, previously lead out under the skin 3 weeks before. Previously, was determined that a tumor visualized in the spleen at 5 weeks, and liver metastases at 7 weeks after transplantation S45. Levels of SOD1, GPO1, GR and MDA were determined using ELISA and DC by biochemical method in spleen and liver homogenates during the latent period of tumor growth and metastasis (1–2 weeks post-transplantation).Results. Significant changes (1.5–5.2 times, р < 0.050–0.001) in studied factors levels were observed compared to intact rats and rats with the spleen lead out. Activation of lipid peroxidation and antioxidant system was noted in the spleen (tumor-carrying organ) during tumor growth and metastasis. At the same time, in the liver (the target organ of metastasis) observed also increased lipid peroxidation but simultaneously a pronounced decreased GR levels (5 times, p < 0.001) without affecting SOD1 levels.Conclusion. Liver tissue exhibited the inferiority of antioxidant protection and the formation of pro-oxidant condition during the latent period of tumor growth, which may prepare the soil for metastasis.

Level of prooxidant-antioxidant status in highly productive cows with comorbid obstetric, gynecological and orthopedic pathology

The lipid peroxidation and antioxidant defense system is a balanced system responsible for the processing and utilization of lipids in the body’s cells. It plays an important role in lipid metabolism, cell protection and overall health of the body. Its proper functioning is necessary to ensure optimal functioning of cells and organs throughout the body. The article clinically and experimentally substantiates the pathogenetic role of lipid peroxidation products and the level of antioxidant protection in cows with endometritis and purulent-necrotic processes in the finger area, as well as with the comorbid course of endometritis and orthopedic pathology. It has been shown that multimorbid manifestation is accompanied by a more severe course than individual diseases. It has been established that the development of postpartum endometritis and purulent-necrotic lesions of the limbs in cows is accompanied by a highly significant increase in lipid peroxidation products in the blood serum against the background of a decrease in the amount of antioxidant enzymes, with the exception of ceruloplasmin. Moreover, these changes are accompanied by a sharp jump in the comorbid course of endometritis and orthopedic pathology in highly productive animals.

Metabolic Syndrome in Reproductive Age Women of Various Ethnic Groups. Neuroendocrine Status and Lipid Peroxidation System.

We analyzed the state of neuroendocrine regulation and LPO-antioxidant defense systems in reproductive age women with metabolic syndrome (MetS), representatives of the Russian and Buryat ethnic groups. Compared to the corresponding control groups, women from the Russian ethnic group with MetS had elevated levels of thyroid-stimulating hormone and free androgen index (FAI) and reduced levels of sex hormone-binding globulin, while women from the Buryat ethnic group had increased levels of prolactin and FAI. Changes in the LPO system in women of the Russian ethnic group with MetS consisted in an increase in the levels of substrates with double bonds, TBA-reactive substances, and fat-soluble vitamins. Buryat women with MetS had a higher content of primary oxidation products and reduced levels of glutathione. The results of the study indicate a hyperandrogenic shift in the neuroendocrine regulation system, as well as compensatory influences from different parts of the antioxidant defense system in women of reproductive age with MetS, depending on their ethnicity. These findings indicate the need for assessing and monitoring the levels of these metabolites in women with MetS, considering their ethnicity.

Ferroptosis and myocardial ischemia-reperfusion: mechanistic insights and new therapeutic perspectives.

Myocardial ischemia-reperfusion injury (MIRI) is a significant factor in the development of cardiac dysfunction following a myocardial infarction. Ferroptosis, a type of regulated cell death driven by iron and marked by lipid peroxidation, has garnered growing interest for its crucial involvement in the pathogenesis of MIRI.This review comprehensively examines the mechanisms of ferroptosis, focusing on its regulation through iron metabolism, lipid peroxidation, VDAC signaling, and antioxidant system dysregulation. We also compare ferroptosis with other forms of cell death to highlight its distinct characteristics. Furthermore, the involvement of ferroptosis in MIRI is examined with a focus on recent discoveries concerning ROS generation, mitochondrial impairment, autophagic processes, ER stress, and non-coding RNA regulation. Lastly, emerging therapeutic strategies that inhibit ferroptosis to mitigate MIRI are reviewed, providing new insights into potential clinical applications.

Effects of Photobiomodulation Application on Glutathione-Related Antioxidant Defense System in Rabbit Eye Tissues.

Photobiomodulation (PBM) has emerged as a potentially effective therapeutic approach to modulate cellular functions. This study aimed to examine the impact of PBM on reactive oxygen species (ROS), lipid peroxidation, and glutathione-related antioxidant defense systems in rabbit eye tissues. A polychromatic light source with an intensity of 2.6 J/cm2/min was used for PBM treatment in New Zealand White rabbits for 12 min. The PBM group (n = 8) received treatments every 2 days for a total of 12 sessions, whereas the control group (n = 8) did not undergo any PBM light exposure during the same period. The application of PBM significantly elevated ROS-mediated glutathione levels, along with increased activities of glutathione peroxidase and reductase, particularly in corneal tissue (p ≤ 0.05). In conclusion, PBM treatment effectively enhances antioxidant defense mechanisms in the eye, particularly in corneal tissue, suggesting its potential as a therapeutic strategy for managing oxidative stress-related ocular conditions.

Cultivar-specific regulation of antioxidant enzyme activity and stomatal closure confer tolerance of wheat to elevated ozone: A two-year open-field study with five cultivars

Elevated concentrations of tropospheric ozone (O3) pose a significant threat to food production in many regions of the world. We conducted a two-year experiment with five winter wheat (Triticum aestivum L.) cultivars, Yangmai16 (Y16), Yangmai23 (Y23), Zhenmai12 (Z12), Yangmai29 (Y29), and Yangmai30 (Y30), to assess photosynthetic traits, lipid peroxidation, and antioxidant systems under ambient (A-O3) or elevated (E-O3; 1.5 times A-O3) O3 in a Free-Air O3Concentration Enrichment system (FACE). E-O3 accelerated leaf senescence, manifested by marked reductions in photosynthetic rate, stomatal conductance, total antioxidant capacity, and photosynthetic pigment content, accompanied by altered antioxidant enzyme activity and a significant increase in malondialdehyde content (an indicator of lipid peroxidation). Most parameters showed significant inter-cultivar differences, as well as interactions between O3 and cultivar. The response of the antioxidant system in wheat flag leaves was influenced by O3 exposure levels. The response of antioxidant enzymes at the grain filling stage and the timely closure of stomata conferred tolerance to O3. This tolerance was associated with higher antioxidant enzyme activity at the anthesis stage but was not related to the size of stomata. This study provides a crucial theoretical foundation for further breeding O3-tolerant cultivars.

Dishomeostatic phenomena in acute pancreatitis of variable severity

Acute pancreatitis remains one of the most dangerous pathologies in the structure of emergency abdominal surgery. This is due to many reasons, including an increase in the frequency of destructive forms of the disease, high mortality, and frequent unfavorable outcomes. The aim of this study was to investigate a number of leading components of homeostasis in patients with acute pancreatitis of varying severity. A retrospective study was conducted on 50 patients with acute pancreatitis of diff erent severity levels who were hospitalized at the Republican Clinical Hospital named after S.V. Katkovа (Saransk, Russia). The patients were divided into groups: the fi rst group (control, n = 30) consisted of patients with mild acute pancreatitis, and the second group (main, n = 20) consisted of patients with severe acute pancreatitis. The study evaluated the endogenous intoxication syndrome, the activity of lipid peroxidation and phospholipase systems, microcirculation status, liver function, and the activity of the coagulation-lytic blood system. The results showed that in the early stages of acute pancreatitis, several pathological processes were observed: the development of endotoxemia syndrome, activation of lipid peroxidation and phospholipase systems, microcirculation disorders, changes in the coagulation and fibrinolytic links of the hemostasis system, and liver function suppression. The severity of these disorders was associated with the severity of the pathology. In cases of mild severity, the changes in the parameters studied were reversible, while in severe cases they were stable and oftenirreversible. The presence of toxemia, oxidative stress, dysmicrocirculation, and hemostatic disorders should be considered as risk factors for disease progression and complications.

Metabolic stress and stress-limiting mechanisms in bronchial asthma combined with type 2 diabetes mellitus

Objective: to study the indicators of lipid peroxidation and the antioxidant system in the blood and moisture condensate of exhaled air in patients with AD combined with type 2 diabetes, and in the blood of these patients — total metabolites of nitric oxide. Materials and methods: the study involved 215 patients with persistent BA of moderate severity aged (38.6±2.4) years, including 88 men (40.9%), 127 women (59.1%). Among the examined patients with BA there were 64 — group I, persons with BA combined with type 2 diabetes — 151 (group II). The parameters of the lipid peroxidation system (LPS) in the blood serum were studied: malondialdehyde (MDA), diene conjugates (DC), and the antioxidant system (AOS) according to the activity of catalase and superoxide dismutase (SOD), the amount of total metabolites of nitric oxide (NOx), in the condensate of exhaled air moisture (KEAM) was determined general oxidant (GOA) and antioxidant (AOA) activity. Results: in patients with BA combined with type 2 diabetes, an increase in the concentration of POL products in the blood was revealed: MDA was 2.6 times (p<0.05) compared with the control group and 1.3 times (p<0.05) compared with the indicator in patients with AD, DC, respectively, 2.0 times (p<0.05) compared with the control group and 1.2 times (p<0.05) compared with I group. The activity of the enzymes AOS catalase and SOD in patients with comorbidity of BA and type 2 diabetes was found to be lower than in patients of group I. In the KEAM of patients with comorbidity of BA and type 2 diabetes, a significant increase in OOA and a decrease in OAA were noted. The concentration of NOx in the blood serum of group II patients was 1.6 times higher than in the control group (p<0.05), but 1.4 times lower than in patients with AD without comorbidity with type 2 diabetes (p<0.05). The direction of the revealed correlations between the products of POL in blood serum and KEAM confirmed the systemic nature of metabolic changes in the body of patients with AD, and their strength in group II patients — the negative effect of comorbid type 2 diabetes on the greater severity of these metabolic changes. Conclusions: the resulting changes in the state of LPS and AOS in the blood and KEAM of patients with BA combined with type 2 diabetes can be characterized as systemic metabolic stress, both components of which: oxidative and nitrosive are supported by insufficient stress-limiting mechanisms — low activity of AOS enzymes and possible depletion of nitric oxide production, which should be reflected in the means of correcting metabolic disorders in patients with this comorbidity.

New opportunities for correction of hormonal disorders and oxidative stress in women with genital endometriosis

Background. Genital endometriosis is one of the most urgent problems of modern gynecology. Considering oxidative stress as a pathogenetic link of endometriosis, we believe it reasonable to use a combined drug containing superoxide dismutase, resveratrol, and zinc. The purpose of the work was to evaluate the effectiveness of the treatment for genital endometriosis supplemented with the use of superoxide dismutase, resveratrol, and zinc, taking into account the leading pathophysiological links of the pathology. Materials and methods. Thirty-seven women of reproductive age with genital endometriosis were under observation. Treatment in the first group was carried out in accordance with the Guideline Development Group recommendations. Thirty-nine women of the second group additionally received a drug containing superoxide dismutase, resveratrol, and zinc. The control group included 30 healthy women. The state of lipid peroxidation processes was assessed by the level of diene conjugates and malondialdehyde in the blood serum and the antioxidant defense system by the content of superoxide dismutase and glutathione peroxidase. To monitor the patients’ quality of life, pain syndrome was studied using the Visual Analogue Scale. Statistical processing of the obtained data was carried out by means of the standard StatSoft Statistica for Windows 13.0 program pac­kage. Results. The assessment of the pain syndrome in the second group showed that it completely disappeared in women with the first stage of the disease. Among patients with the second stage, pain disappeared in 8 cases, 3 patients had a decrease from severe to mild pain. At the third stage, pain disappeared completely in 5 women, in 4 cases, it decreased from severe to mild, and in one woman, the pain decreased from unbearable to mild. All patients of the second group noted a decrease in pain during intercourse, and in the first stage — its absence, an increase in work capacity (r = 0.64, p < 0.01), a decrease in irritability and anxiety in the perimenstrual period (r = –0.59, p < 0.05) and overall satisfaction with the treatment result. Side effects were not noted in any of the patients. Conclusions. Improving treatment for genital endometriosis by supplementing therapy with superoxide dismutase, resveratrol, and zinc is pathogenetically justified, as it has a significant positive effect on the lipid peroxidation and antioxidant defense system, compared to the traditional treatment regimen.

Marine Polysaccharides Carrageenans Enhance Eryptosis and Alter Lipid Order of Cell Membranes in Erythrocytes.

Carrageenans of ι-, κ- and λ-types were incubated with washed erythrocytes (hematocrit 0.4%) at 0-1-5-10 g/L for either 24 h or 48 h. Incubation was followed by flow cytometry-based quantitative analysis of eryptosis parameters, including cell volume, cell membrane scrambling and reactive oxygen species (ROS) production, lipid peroxidation markers and confocal microscopy-based evaluation of intracellular Ca2+ levels, assessment of lipid order in cell membranes and the glutathione antioxidant system. Confocal microscopy was used to assess carrageenan cellular internalization using rhodamine B isothiocyanate-conjugated carrageenans. All three types of carrageenans were found to trigger eryptosis. Pro-eryptotic properties were type-dependent and λ-carrageenan had the strongest impact inducing phosphatidylserine membrane asymmetry, changes in cell volume, Ca2+ signaling and oxidative stress characterized by ROS overproduction, activation of lipid peroxidation and severe glutathione system depletion. Eryptosis induction by carrageenans does not require their uptake by erythrocytes. Changes in physicochemical properties of cell membrane were also type-dependent. No carrageenan-induced generation of superoxide and hydroxyl radicals was observed in cell-free milieu. Our findings suggest that ι-, κ- and λ-types trigger eryptosis in a type-dependent manner and indicate that carrageenans can be further investigated as potential eryptosis-regulating therapeutic agents.

The developing brain in the formation of oxidant and antioxidant systems

BACKGROUND: The structures, tissues, and systems of the brain differentiate gradually. The values of biochemical constants vary depending on the timing of development, that is, the embryonic, early, and late postnatal periods. In this respect, the multicomponent oxidation and antioxidation systems that do not mature at the same time are of interest.
 AIM: To examine the processes of lipid peroxidation based on the level of malonic dialdehyde and antioxidant protection (superoxide dismutase, catalase, and reduced glutathione) in the brain of rat embryos and offspring at different periods of pre- and postnatal development.
 MATERIALS AND METHODS: Thirty-nine pregnant female Wistar rats weighing 220–250 g were selected, from which 176 embryos and rat pups of different sexes and age were obtained, including embryos in the third trimester of pregnancy (13–17 days of gestation) and rat pups aged 1–14 weeks. The concentration of malonic dialdehyde (indicator of lipid peroxidation) was determined in the brain tissue, and the activity of superoxide dismutase, catalase, and level of reduced glutathione was found as indicators of antioxidant defense systems.
 RESULTS: The brains of the embryos were characterized by low levels of malonic dialdehyde, and its concentration sharply increased immediately after the birth of rat pups. A similar but a less pronounced pattern was also recorded for indicators of antioxidant protection (superoxide dismutase activity and level of reduced glutathione). The opposite reaction was observed in catalase, which demonstrated high activity in the brain in the prenatal period but significantly decreased after birth. With further postnatal development up to sexual maturity (14 weeks, or 3 months of age), no significant changes in the activities of superoxide dismutase, catalase, and concentration of reduced glutathione were noted; however, a twofold drop in the level of malonic dialdehyde in the brain was noted.
 CONCLUSION:Already in the first months of life in rats, a quite stable status of lipid peroxidation and antioxidant defense systems of the brain tissue developed.

Endoplasmic Reticulum Protein TXNDC5 Interacts with PRDX6 and HSPA9 to Regulate Glutathione Metabolism and Lipid Peroxidation in the Hepatic AML12 Cell Line.

Non-alcoholic fatty liver disease or steatosis is an accumulation of fat in the liver. Increased amounts of non-esterified fatty acids, calcium deficiency, or insulin resistance may disturb endoplasmic reticulum (ER) homeostasis, which leads to the abnormal accumulation of misfolded proteins, activating the unfolded protein response. The ER is the primary location site for chaperones like thioredoxin domain-containing 5 (TXNDC5). Glutathione participates in cellular oxidative stress, and its interaction with TXNDC5 in the ER may decrease the disulfide bonds of this protein. In addition, glutathione is utilized by glutathione peroxidases to inactivate oxidized lipids. To characterize proteins interacting with TXNDC5, immunoprecipitation and liquid chromatography-mass spectrometry were used. Lipid peroxidation, reduced glutathione, inducible phospholipase A2 (iPLA2) and hepatic transcriptome were assessed in the AML12 and TXNDC5-deficient AML12 cell lines. The results showed that HSPA9 and PRDX6 interact with TXNDC5 in AML12 cells. In addition, TXNDC5 deficiency reduced the protein levels of PRDX6 and HSPA9 in AML12. Moreover, lipid peroxidation, glutathione and iPLA2 activities were significantly decreased in TXNDC5-deficient cells, and to find the cause of the PRDX6 protein reduction, proteasome suppression revealed no considerable effect on it. Finally, hepatic transcripts connected to PRDX6 and HSPA9 indicated an increase in the Dnaja3, Mfn2 and Prdx5 and a decrease in Npm1, Oplah, Gstp3, Gstm6, Gstt1, Serpina1a, Serpina1b, Serpina3m, Hsp90aa1 and Rps14 mRNA levels in AML12 KO cells. In conclusion, the lipid peroxidation system and glutathione mechanism in AML12 cells may be disrupted by the absence of TXNDC5, a novel protein-protein interacting partner of PRDX6 and HSPA9.

ANTIOXIDANT DEFICIENCY AS PREECLAMPSIA RISK FACTOR

The aim – to study the state of the processes of lipid peroxidation (LPO) and theantioxidant system (AOS) of protection in pregnant women with different degrees ofpreeclampsia severity(PE).Materials and methods. LPO and AOS indicators were studied at 24-26 and 34-36 weeksof pregnancy in 20 healthy women with a physiological course of pregnancy (controlgroup) and in 34 women with PE (main group). 20 of them- with moderate PE (groupI) and 14 – with severe PE (group II).The results. When studying the processes of POL-AOS in pregnant women of all groups,a reliable increase in POL was found, which was more significant in the main group(Р˂0.001). In response to the activation of LPO processes in the control group, the activationof the AOS components of blood protection occurred, as evidenced by an increase in thelevel of glutathione (Р˂0.02) and glutathione peroxidase (Р˂0.05). This contributes to theneutralization of POL products. In pregnant women of the I group, at 24-26 weeks, the levelof glutathione and glutathione- peroxidase increased (Р˂0.02 and Р˂0.01, respectively), andat 34-36 weeks, these indicators did not differ from the control (Р>0.05). In women of theII group, against a background of an increase in the level of lipoperoxidation products, theindicator of glutathione peroxidase did not increase reliably (Р>0.05). The level of glutathionein 24-26 weeks also did not increase (Р>0.05), and in 34-36 – significantly decreased.Conclusions. In women with moderate PE at 34-36 weeks of pregnancy, there is anantioxidant deficiency and a decrease in compensatory and adaptive mechanisms.Exhaustion of the body’s antioxidant defense system was found in pregnant women withsevere PE. Violation of AOS function against a background of hyperproduction of lipidhydroperoxides can lead to oxidative stress, disruption of compensatory and adaptivemechanisms and the development of pathological conditions in the mother and fetus.Preclinical diagnosis and correction of disorders of POL-AOS processes will give anopportunity to prevent the development of severe PE.

Insights into mechanisms of seed longevity in soybean: a review.

Soybean, a crop of international importance, is challenged with the problem of seed longevity mainly due to its genetic composition and associated environmental cues. Soybean's fragile seed coat coupled with poor DNA integrity, ribosomal dysfunction, lipid peroxidation and poor antioxidant system constitute the rationale for fast deterioration. Variability among the genotypes for sensitivity to field weathering contributed to their differential seed longevity. Proportion and density of seed coat, glassy state of cells, calcium and lignin content, pore number, space between seed coat and cotyledon are some seed related traits that are strongly correlated to longevity. Further, efficient antioxidant system, surplus protective proteins, effective nucleotide and protein repair systems and free radical scavenging mechanisms also contributed to the storage potential of soybean seeds. Identification of molecular markers and QTLs associated with these mechanisms will pave way for enhanced selection efficiency for seed longevity in soybean breeding programs. This review reflects on the morphological, biochemical and molecular bases of seed longevity along with pointers on harvest, processing and storage strategies for extending vigour and viability in soybean.

Preclinical evaluation of a gel composition based on a flavonoid complex for the treatment of periodontal diseases in orthodontic patients

The aim of the work was a preclinical assessment of acute toxicity, skin resorptive, irritant effects, cumulative and catalase activity, as well as sensitizing properties of the local gel composition “Benzidaflaziverdine” (GCB) used for the treatment of periodontal diseases in orthodontic patients. Materials and methods. 119 animals were involved in the experiment, assigned to seven main and two control groups. GCB was administered intragastrically in doses of 300–600 mg/kg and intradermally of 200 μg into the outer surface of the ear. The native solution of GCB was applied to the skin and mucous membranes, administered orally by the method of “subchronic toxicity” and to the surface of the chorioallantoic membrane (CAM) of chicken embryos. The intensity of lipid peroxidation (LPO) was assessed by the level of diene conjugates (DCs) and malondialdehyde (MDA), and the antioxidant system by catalase activity. The specific leukocyte agglomeration reaction (SLAR), the specific leukocyte lysis reaction, and neutrophil damage indicators were used. Results. The median lethal dose LD50 for rats and mice of both sexes exceeded 5000 mg/kg. The irritant effect of GCB on the mucous membranes was manifested by hyperemia on the second day. Symptoms of irritation disappeared after 3–4 days without medical intervention. An analysis of the CAM blood vessels after exposure to GCB in two observations at the 120th second showed the beginning of hemorrhages. In one observation, GCB caused minor hemorrhages at the 300th second of the experiment. It was found that the coefficient of GCB irritant action was 5 (the mean score of Me (Q1; Q3) was 5 (4; 5)). The coefficient of cumulation (Kcum) exceeded 8.2. An insignificant increase in the median or mean values of catalase enzyme activity, DCs, and the amount of LPO end product such as MDA was observed compared to the control group animals. The SLAR test indicated the development of a delayed-type allergic reaction under the influence of GCB in a 1:10 dilution. One-hundred-fold dilution did not cause significant changes in the indicator in the main group compared to the control one. Conclusions. GCB belongs to the 4th class of toxicity – practically non-toxic substances, does not have sex- and species sensitivity, has weak cumulative activity, minimal effect on the system of LPO. GCB can be recommended for the use in clinical periodontology for medical support of orthodontic patients.

Correlation between the Chemiluminescent Activity of Neutrophilic Granulocytes and the Lipid Peroxidation-Antioxidant Defense System in Gastric Cancer Associated with Helicobacter pylori Infection.

To study the processes of lipid peroxidation and the activity of antioxidant defense enzymes depending on the chemiluminescent activity of neutrophilic granulocytes in patients with gastric cancer associated with H. pylori infection, depending on the stage. A total of 39 patients with stage I-II gastric cancer and 30 patients with stage III-IV gastric cancer were examined. A study of the chemiluminescent activity of neutrophilic granulocytes was carried out and the parameters of the lipid peroxidation system and antioxidant protection in plasma were determined using the spectrophotometric method. Statistical data processing was performed using the Statistica 7.0 software package (StatSoft, St Tulsa, OK, USA). In patients with gastric cancer associated with H. pylori infection, regardless of stage, the proportion of neutrophilic granulocytes with normal activity did not exceed 1/3 of the total number of patients, and the remaining 2/3 of patients had altered chemiluminescent activity of neutrophilic granulocytes. In patients with gastric cancer, by I-II stage of the disease, the majority revealed a reduced function of neutrophilic granulocytes, and in patients with gastric cancer in stage III-IV of the disease, the majority showed increased chemiluminescent activity of neutrophilic granulocytes. In all patients with gastric cancer associated with H. pylori infection, regardless of the stage of the disease, an increase in lipid peroxidation processes with activation of antioxidant defense enzymes was detected. At the same time, there were no statistically significant differences between the indicators of the system lipid peroxidation-antioxidant protection depending on the stage of gastric cancer and the chemiluminescent activity of neutrophilic granulocytes, which likely indicates that all reactive oxygen species produced by neutrophilic granulocytes in the respiratory burst are consumed locally, minimally affecting the development of oxidative stress in the blood plasma.

A relation between specific immune status indicators and activity of “lipid peroxidation — antioxidant defense” system in COVID-19 neonates

The 2019 coronavirus infection (COVID-19) has not been considered as a solved issue for public health. Pregnant women and newborns are specifically vulnerable to COVID-19 infection compared to older children and healthy young adults. Virtually no data on relation between diverse arms of immunity in patients in neonatal period and coronavirus infection are available. The obtained results can contribute to a better understanding of the pathogenetic mechanisms on reactivity of immune processes in young patients and corresponding formation of approaches for prevention and correction of such disorders. The aim of the study was to determine magnitude of specific altered parameters in immune system and their relation with lipid peroxidation parameters in COVID-19 newborns. Two groups of newborns (mean age 43.1 days) were examined: SARS-CoV-2-positive (COVID-19 patients, n = 44) and negative (control group, n = 80) PCR test of nasopharyngeal swab. All newborns were assessed for specific indicators of peripheral blood immune status and lipid peroxidation activity. The concentration of Th1-pro-inflammatory cytokines and Th2-anti-inflammatory interleukins was assessed by enzyme immunoassay method (a panel of monoclonal antibodies). Spectrophotometric, fluorometric and enzyme immunoassay methods to evaluate the lipid peroxidation system were used. According to our data, newborns with COVID-19 vs. healthy newborns had decreased CRP, pro-inflammatory cytokines TNF, IL-1, IL-6, IL-8, and anti-inflammatory factor (IL-4). Change in lipid peroxidation system in children with COVID-was 19 related to higher level of DC, KD and CT, TBARs, increased SOD activity and reduced GPO. Numerous intersystem dependencies in the group of newborns with COVID-19 (CRP Total AOA, IL-4 KD and CT, IL-4 TBARs, IL-4 Total AOA, IL-4 SOD, IL-8 SOD, IFN GSH) were noted. It can be concluded that in newborns with COVID-19, changes in the immune system are nonspecific and are accompanied by an increased intensity of lipid peroxidation reactions against the background of reduced values of pro- and anti-inflammatory cytokines. These results may contribute to a more accurate assessment of intensity and dynamics of emerging neonatal coronavirus infection, which should be an important arm in preventing subsequent complications.

Deoxynivalenol induces testicular ferroptosis by regulating the Nrf2/System Xc-/GPX4 axis.

Deoxynivalenol (DON) is the most common mycotoxin contaminant in food and feed. DON accumulation in food chain severely threatens human and animal health due to the toxic effects on the reproduction system. However, the underlying mechanism of DON on male reproductive dysfunction is still in debate and there is little information about whether DON triggers testicular ferroptosis. In this study, male C57BL/6 mice were divided into 4 groups and treated by oral gavage with 0, 0.5, 1.0, 2.0 mg/kg BW DON for 28 days. Firstly, we proved that male reproduction dysfunction was induced by DON through assessing testicular histopathology, serum testosterone level as well as blood-testis barrier integrity. Then, we verified ferroptosis occurred in DON-induced testicular dysfunction model through disrupting iron homeostasis, increasing lipid peroxidation and inhibiting system Xc-/Gpx4 axis. Notably, the present data showed DON reduced antioxidant capacity via blocking Nrf2 pathway to lead to the further weakness of ferroptosis resistance. Altogether, these results indicated that DON caused mice testicular ferroptosis associated with inhibiting Nrf2/System Xc-/GPx4 axis, which provided that maintaining testicular iron homeostasis and activating Nrf2 pathway may be a potential target for alleviating testicular toxicity of DON in the future.