Lipid Peroxidation Processes Research Articles

Ferroptosis regulates hemolysis in stored murine and human red blood cells.

Red blood cell (RBC) metabolism regulates hemolysis during aging in vivo and in the blood bank. However, the genetic underpinnings of RBC metabolic heterogeneity and extravascular hemolysis at population scale are incompletely understood. Based on the breeding of 8 founder strains with extreme genetic diversity, the Jackson laboratory diversity outbred population can capture the impact of genetic heterogeneity in like fashion to population-based studies. RBCs from 350 outbred mice, either fresh or stored for 7 days, were tested for post-transfusion recovery, as well as metabolomics and lipidomics analyses. Metabolite and lipid Quantitative Trait Loci (QTL) mapped >400 gene-metabolite associations, which we collated into an online interactive portal. Relevant to RBC storage, we identified a QTL hotspot on chromosome 1, mapping on the region coding for the ferrireductase Steap3, a transcriptional target to p53. Steap3 regulated post-transfusion recovery, contributing to a ferroptosis-like process of lipid peroxidation, as validated via genetic manipulation in mice. Translational validation of murine findings in humans, STEAP3 polymorphisms were associated with RBC iron content, lipid peroxidation and in vitro hemolysis in 13,091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. QTL analyses in humans identified a network of gene products (FADS1/2, EPHX2, LPCAT3, SLC22A16, G6PD, ELOVL, PLA2G6) associated with lower levels of oxylipins. These polymorphisms were prevalent in donors of African descent and were linked to allele frequency of hemolysis-linked polymorphisms for Steap3 or p53. These genetic variants were also associated with lower hemoglobin increments in thousands of single-unit transfusion recipients from the vein-to-vein database.

Hepatic Failure in Pancreonecrosis and the Development of Abdominal Sepsis

It is well known that acute destructive pancreatitis, pancreonecrosis is accompanied by severe endogenous intoxication, often leading to the development of multiple organ failure syndrome, liver failure is one of the important links in this process. The mortality rate of patients with pancreonecrosis related to liver failure is as high as 83%, and approximately 5% of patients with pancreonecrosis have fulminant liver failure. Proven: liver function is closely related to the progression of purulent-necrotic complications in patients with acute destructive pancreonecrosis. The authors present the data of literature on the importance of liver failure in the course and prognosis of acute destructive pancreatitis. The pathogenetic role of lipid peroxidation processes are especially emphasized. The controversial issues of portal and systemic bacteremia and toxemia in the development of pancreatogenic abdominal sepsis are discussed, as well as the involvement of the lymphatic system. The authors’ research aims to analytically dissect and summarize the processes underlying the clinical manifestations of liver failure in pancreatic necrosis and their underlying mechanisms, which may provide new insights for further understanding and better management of liver failure in patients with pancreatic necrosis and abdominal sepsis.

A simultaneous analysis strategy of glycerophospholipids and lipid mediators based on secondary extraction scheme.

Lipid peroxidation plays an important role in physiological and pathophysiological conditions; it occurs mainly in the vicinity of the membrane. Glycerophospholipids are indispensable for normal structure of membranes. Lipid mediators are final products of lipid peroxidation. Glycerophospholipids as a source of lipid mediators are closely related with lipid mediators in lipid peroxidation process. This study developed a strategy for simultaneous analysis of glycerophospholipids and lipid mediators in a sample based on a secondary extraction scheme. Due to differences in physicochemical properties of glycerophospholipids and lipid mediators, we used different solvents and methods to extract glycerophospholipids and lipid mediators based on a sample. In addition, we compared three methods of extracting glycerophospholipids to select the best extraction method. In this study, a UPLC-MRM absolute quantification strategy for three deuterated internal standards of lipid mediator was established. The calibration range of all standards is linear, and the correlation coefficients are greater than 0.999. Quantitative range, precision, and accuracy of all analytes-based analysis method meet requirements of method validation. And the accuracy and precision of this method for glycerophospholipids meet the requirements of method verification. It is satisfactory to apply this method in the analysis of the changes of enzymes in lipid peroxidation during the treatment of asthma with dexamethasone. The quantitative results of phospholipids and lipid mediators in mouse lung tissue were obtained by this method, indicating that dexamethasone may inhibit the activity of phospholipase As enzyme and thus slow down the lipid peroxidation process. This work may be of great significance for exploring the changes of enzymes in lipid peroxidation metabolism.

PH-activated metal–organic layer nanozyme for ferroptosis tumor therapy

Nanozymes have made great achievements in the research of tumor therapy. However, due to the complex tumor microenvironment, the catalytic activity and biosafety of nanozymes are limited. High catalytic efficiency is a relentless pursuit for the preparation of high-performance nanozymes. Dimensional reduction from 3D nanoscale metal–organic frameworks (nMOFs) to 2D nanoscale metal–organic layers (nMOLs) increases the encounters frequency of nanozymes and substrate, which facilitates the diffusion of reactive oxygen species (ROS) from nMOLs, thus significantly improving the effectiveness of chemodynamic therapy. In this study, He@Ce-BTC nMOF and He@Ce-BTB nMOL based on Ce6 SBUs were synthesized by solvothermal reaction. Compared with the 3D nMOFs, the 2D nanozymes He@Ce-BTB nMOL possessed enhanced ROS catalytic efficiency, were able to be activated by the tumor acidic microenvironment with the polymerase mimetic activities (CAT, POD, GSH-OXD) that enhances the lipid peroxidation process and accelerates the process of ferroptosis thereby killing tumor cells. In addition, He@Ce-BTB does not affect normal tissue cells, thus avoiding diffusion-induced side effects. He@Ce-BTB has shown excellent therapeutic effects in vitro and in vivo, which indicates its potential for clinical application, and is expected to become a new generation of drugs for the treatment of tumors.

Method of intensification of digestive and intermediary metabolism in meat quails during denitrification

Sorbents are characterized by synergistic action with many biologically active compounds, including antioxidants that neutralize free radicals in the body, prevent membrane damage, and preserve the youth of the cells of organs and tissues of poultry. The purpose of the study was to determine the eff ect of the sorbent Mikosorb®A Plus and the antioxidant Hadox on the parameters of digestive and intermediary metabolism in meat quails when they are added to compound feed with a subtoxic dose of nitrates. It was found that in order to improve the digestive and intermediary metabolism in meat quails, the composition of their compound feed should include the drugs of the sorbent Mikosorb®A Plus at the dose of 1000 g/t and the antioxidant Hadox at the dose of 150 g/t of compound feed. These drugs allowed to increase signifi cantly (p < 0.05) the coeffi cients of dry matter digestibility by 3.43 abs.%, organic matter by 3.33 abs.%, crude protein by 3.55 abs.%, crude fi ber by 3.48 abs.% and nitrogen-free extractive substances by 3.57 abs.% in the quails of the 3rd experimental group compared to the control group. This also allowed to increase the number of erythrocytes in the blood of quails of the 3rd experimental group by 0.56×1012/l (p < 0.05), hemoglobin by 7.0 g/l (p < 0.05) with a simultaneous decrease in methemoglobin by 1.40 % (p < 0.05) compared to the control analogues. In the quails of the 3rd experimental group, the concentration of total protein in the blood serum was higher by 5.20 g/l (p < 0.05) with a simultaneous decrease in the content of nitrates by 1.63 times (p < 0.05) and nitrites by 2.47 times (p < 0.05) compared to the quails of the control group. Joint feeding of the sorbent and antioxidant inhibited lipid peroxidation processes and had a stimulating eff ect on the antioxidant defense mechanism in the quail body. At the same time, the quails of the 3rd experimental group had a lower proportion of conjugated dienes by 40.54 % and malondialdehyde by 28.72 % compared to the control group.

Increased NPM1 inhibit ferroptosis and aggravate renal fibrosis via Nrf2 pathway in chronic kidney disease

Recent findings underscore the significance of ferroptosis, an innovative iron-dependent mode of cell death, in the etiology and progression of chronic kidney disease (CKD). Nucleophosmin 1 (NPM1), a nucleolar protein, contributes to fibrogenesis and modulates cellular functions and mortality. Initial investigations utilized bioinformatics techniques to pinpoint genes with altered expression in CKD and to forecast the potential links between NPM1, ferroptosis, and renal fibrosis. Increased NPM1 expression was verified in the renal tissues of CKD patients. Experimental models of renal fibrosis in both animals and cells were then used for further study. The suppression of NPM1 led to an augmentation in iron metabolism and lipid peroxidation processes integral to ferroptosis, contributing to the mitigation of renal fibrosis. In contrast, an elevation in NPM1 expression had the opposite effect. This modulation may be interconnected with the nuclear factor erythroid 2–related factor 2 pathway. Moreover, the application of the ferroptosis inhibitor, Fer-1, not only obstructed ferroptosis but also diminished NPM1 expression, which, in turn, contributed to the alleviation of renal fibrosis. Thus, our findings suggest that in CKD the NPM1 level increased and led to decreased ferroptosis and aggravated renal fibrosis via an Nrf2 pathway. Ferroptosis inhibitor can alleviate renal fibrosis.

New Insights into the Mechanisms of Toxicity of Aging Microplastics.

Nowadays, synthetic polymer (plastic) particles are ubiquitous in the environment. It is known that for several decades microplastics (MPs) have been accumulating in the World Ocean, becoming available to a large variety of marine organisms. Particularly alarming is the accumulation of aging plastic particles, as the degradation processes of such particles increase their toxicity. The diverse display of negative properties of aging MPs and its effect on biota are still poorly understood. In this study, in vitro experiments modeling the interaction of pristine and UV-irradiated aging polypropylene (PP) fragments with hemocytes and mitochondria of bivalve mollusks Mytilus sp. were performed. The appearance of free radicals in the environment was recorded by spectral characteristics of indicator dyes-methylene blue (MB) and nitroblue tetrazolium (NBT). It was found that due to photooxidation, aging PP fragments sorbed more than threefold MB on their modified surface compared to pristine samples of this polymer. Using NBT, the formation of reactive oxygen species in seawater in the presence of pristine and photoactivated PP was recorded. It was also found that photodegraded PP fragments largely stimulated the development of lipid peroxidation processes in mitochondrial membranes and reduced the stability of hemocyte lysosome membranes compared to pristine PP fragments. In general, the results obtained concretize and supplement with experimental data the previously stated hypothesis of toxicity of aging MPs.

The pro-oxidant-antioxidant ratio in the cells of plant seedlings from various ecological and geographical growth locations

The balance of pro-antioxidants within the cells of common fir (Abies alba) and mugwort (Artemisia vulgaris) seedlings cultivated across eight distinct climatogeographical regions of Russia and Kharkov (Ukraine) was investigated. The intensity of lipid peroxidation processes was recorded as a pro-oxidant response, and the antioxidant response was measured by assessing the total content of low-molecular-weight antioxidants and the activity of superoxide dismutase. An assessment of the pro-antioxidant balance within the cellular structures of seedlings, originating from seeds of plants grown in diverse climatogeographical environments, was performed. This evaluation included the analysis of seedling survival rates, the degree of lipid peroxidation, and the activity of the antioxidant system, utilizing the coefficient method for measurement. The results suggest that the regions from which plant seeds were collected can be classified into three distinct zones according to the values of the extremity coefficient. A significant positive correlation was identified between the activity of superoxide dismutase in the cells of the examined seedlings and the levels of solar insolation in the regions where the seeds were collected. Adaptation changes in wild plants to temperature, humidity, and light conditions lead to the activation of antioxidant systems. The seedlings of plants whose seeds were formed in environments characterized by high insolation and low precipitation (such as Yakutsk, Ulan-Ude, and Srednekolymsk) exhibited a low total antioxidant content, accompanied by a compensatory increase in superoxide dismutase activity. Our research indicates that the survival rates of seedlings of common fir and mugwort are contingent upon the pro-antioxidant balance that has developed in response to the climatic conditions experienced by the plants. This relationship is characterized by species specificity, nonlinear dynamics, and is predominantly affected by the volume of precipitation received during the active growing season of the maternal plants.

Ferroptosis and Sarcopenia-Osteoporosis after Menopause: Research Status, Traditional Chinese Medicine Strategies, and Prospects

Ferroptosis, a precisely regulated cell death mechanism, is distinguished by its intimate link to iron overload and lipid peroxidation processes, playing a pivotal role in the pathological progression of a wide range of diseases. In postmenopausal women suffering from osteoporosis, reduced muscle strength and impaired balance lead to a heightened risk of fragility fractures, markedly diminishing their quality of life. Recent groundbreaking research has underscored the crucial role of the ferroptosis mechanism in the initiation and progression of musculoskeletal diseases. This discovery not only enriches our understanding of disease mechanisms but also heralds ferroptosis pathways as novel and promising therapeutic targets for treating these conditions. Traditional Chinese Medicine (TCM) has exhibited remarkable efficacy in managing musculoskeletal diseases, with studies validating its ability to modulate ferroptosis mechanisms and profoundly impact disease regulation. This portends vast research potential and significant therapeutic promise for the future. By delving deeper into the interplay between ferroptosis and sarcopenia-osteoporosis in postmenopausal women, and by developing innovative therapeutic strategies and TCM interventions, we aspire to forge new pathways for the treatment of sarcopenia-osteoporosis in this patient population.

The Effects of Photodynamic Therapy with Low-Level Diode Laser Compared with Doxorubicin on HT-29 Colorectal Adenocarcinoma Cells Viability.

Background and Objective: Colorectal adenocarcinoma is considered one of the major causes of cancer-related lethality among other type of malignancies. Given the several limitations and adverse outcomes of conventional therapeutic regimens against colorectal cancer, the focus of many investigations has been attributed to the introduction of a novel combined regimen with harmless agents. The purpose of the present study was to investigate the effect of combined doxorubicin (DOX) treatment and photodynamic therapy (PDT) on colorectal adenocarcinoma cells. Material and Methods: HT-29 cells were exposed to different concentrations of DOX, low-level (630 nm) diode laser, and methylene blue (MB) as a photosensitizer substrate separately and a combination of them. The cytotoxic effect of the DOX, laser, MB, and their combination and the IC50 value for each treatment group were calculated by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT). The malondialdehyde (MDA) content as a biomarker of the lipid peroxidation process and liberated lactate dehydrogenase (LDH) enzyme into supernatant was determined. Results: The results of our study evidenced that a combination of photodynamic light (laser plus MB) and DOX caused a significant reduction in the percentage of HT-29 viable cells compared with control and other treatment groups. In addition, this mentioned combination led to a considerable decrease in IC50 of DOX. Increased cell membrane lipid peroxidation and cell destruction processes in the combination therapy group were proven through significant elevation of MDA content and LDH activity in the medium, respectively. Conclusion: The findings of the present study suggested that DOX combined with PDT had a better therapeutic impact on HT-29 colorectal adenocarcinoma cells. Hence, the simultaneous application of PDT along with antineoplastic drugs improves the chemosensitivity of cancerous cells via the disruption of their membrane and triggering death processes that lead to the decrease of chemotherapeutic agents required doses and undesirable effects.

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments.

A series of new RS-, RS-CH2- and R2N-CH2-functionalized сatechols with heterocyclic fragments such as 1,3,4-oxadiazole, 1,2,4-triazole, thiazole, or pyridine were synthesized by the reaction of 3,5-di-tert-butyl-o-benzoquinone or 3,5-di-tert-butyl-6-methoxymethylcatechol with different heterocyclic thiols. The S-functionalized catechols were prepared by the Michael reaction from 3,5-di-tert-butyl-o-benzoquinone and the corresponding thiols. The starting reagents such as substituted 1,3,4-oxadiazole-2-thiols and 4H-triazole-3-thiols are characterized by thiol-thione tautomerism, therefore their reactions with 3,5-di-tert-butyl-6-methoxymethylcatechol can proceed at the sulfur or nitrogen atom. In the case of mercapto-derivatives of thiazole or pyridine, this process leads to the formation of the corresponding thioethers with a methylene linker. At the same time, thiolated 1,3,4-oxadiazole or 1,2,4-triazole undergo alkylation at the nitrogen atom in the reaction with 3,5-di-tert-butyl-6-methoxymethylcatechol to form the corresponding thiones. The yield of reaction products ranges from 42 to 80%. The crystal structures of catechols with 3-nitropyridine or 1,3,4-oxadiazole-2(3H)-thione moieties were established by single-crystal X-ray analysis. The possibility of forming intra- and intermolecular hydrogen bonds has been established for these compounds. The electrochemical behavior of the studied compounds is influenced by several factors: the nature of the heterocycle and its substituents, the presence of a sulfur atom in the catechol ring, or a thione group in the heterocyclic core. The radical scavenging activity and antioxidant properties were determined using the reaction with synthetic radicals, the cupric reducing antioxidant capacity assay, the inhibition process of superoxide radical anion formation by xanthine oxidase, and the process of lipid peroxidation of rat liver (Wistar) homogenates in vitro.

8-weeks aerobic exercise ameliorates cognitive deficit and mitigates ferroptosis triggered by iron overload in the prefrontal cortex of APP Swe/PSEN 1dE9 mice through Xc-/GPx4 pathway.

Alzheimer's disease (AD) is a degenerative disorder of the central nervous system characterized by notable pathological features such as neurofibrillary tangles and amyloid beta deposition. Additionally, the significant iron accumulation in the brain is another important pathological hallmark of AD. Exercise can play a positive role in ameliorating AD, but the mechanism is unclear. The purpose of the study is to explore the effect of regular aerobic exercise iron homeostasis and lipid antioxidant pathway regarding ferroptosis in the prefrontal cortex (PFC) of APP Swe/PSEN 1dE9 (APP/PS1) mice. Eighty 6-month-old C57BL/6 J and APP/PS1 mice were divided equally into 8-weeks aerobic exercise groups and sedentary groups. Subsequently, Y-maze, Morris water maze test, iron ion detection by probe, Western Blot, ELISA, RT-qPCR, HE, Nissle, Prussian Blue, IHC, IF, and FJ-C staining experiments were conducted to quantitatively assess the behavioral performance, iron levels, iron-metabolism-related proteins, lipid antioxidant-related proteins and morphology in each group of mice. In APP/PS1 mice, the increase in heme input proteins and heme oxygenase lead to the elevated levels of free iron in the PFC. The decrease in ferritin content by ferritin autophagy fails to meet the storage needs for excess free iron within the nerve cells. Ultimately, the increase of free ferrous iron triggers the Fenton reaction, may lead to ferroptosis and resulting in cognitive impairment in APP/PS1 mice. However, 8-weeks aerobic exercise induce upregulation of the Xc-/GPx4 pathway, which can reverse the lipid peroxidation process, thereby inhibiting ferroptosis in APP/PS1 mice. 8 weeks aerobic exercise can improve learning and memory abilities in AD, upregulate GPx4/Xc- pathway in PFC to reduce ferroptosis induced by AD.

Relationship between mean monthly February temperature and the level of oxidative processes in immunocompetent organs of bream of Rybinsk reservoir in different years

The intensity of oxidative processes in immunocompetent organs of immature bream Abramis brama L. with an average weight of 375±30 g and length of 290±20 cm was studied. The fish were caught with shuttle nets in the Volga Plec of the Rybinsk reservoir in different years in terms of average daily temperature conditions. After autopsy, samples of immunocompetent organs (kidney, spleen and liver) were taken from captured fish into sterile tubes. Samples were then frozen and stored in a freezer at minus 18–20 °C until processing time. In laboratory conditions, samples were thawed at room temperature immediately before analysis. For further studies, homogenate was prepared from kidney, spleen and liver tissues using a homogenizer with physiological solution in the ratio of 1:1. In the homogenates the content of lipid peroxidation products was studied by the content of malonic dialdehyde and the level of antioxidant defense by the index of inhibition of substrate oxidation. The interannual variability of the studied parameters was noted, associated with ecological and climatic conditions, in particular, with temperature. The most significant differences of the studied biochemical parameters were revealed in the year with the highest temperature conditions compared to the year with the lowest temperature. The lowest values of malonic dialdehyde and substrate oxidation constant were observed in fish in the year with the lowest average daily temperature. In warmer year intensification of lipid peroxidation processes and decrease of antioxidant defense level in the studied organs were observed. The results obtained can be used in monitoring the impact of climatic factors on the physiological and biochemical status of fish.

Synthesis, Structure, Electrochemical Properties, and Antioxidant Activity of Organogermanium(IV) Catecholate Complexes.

A series of novel organogermanium(IV) catecholates 1-9 of the general formula R'2Ge(Cat), where R' = Ph, Et, have been synthesized. Compounds were characterized by 1H, 13C NMR, IR spectroscopy, and elemental analysis. The molecular structures of 1-3, 6, and 8 in crystal state were established using single-crystal X-ray analysis. The complexes are tetracoordinate germanium(IV) compounds containing a dioxolene ligand in a dianion (catecholato) form. Electrochemical transformations of target germanium(IV) complexes have been studied by cyclic voltammetry. The electro-oxidation mechanism of complexes 1-5, 7, and 10 (the related complex Ph2Ge(3,5-Cat) where 3,5-Cat is 3,5-di-tert-butylcatecholate) involves the consecutive formation of mono- and dicationic derivatives containing the oxidized forms of redox-active ligands. The stability of the generated monocations depends both on the hydrocarbon groups at the germanium atom and on the substituents in the catecholate ring. Compounds 6, 8, and 9 are oxidized irreversibly under the electrochemical conditions with the formation of unstable complexes. The radical scavenging activity and antioxidant properties of new complexes were estimated in the reaction with DPPH radical, ABTS radical cation, and CUPRACTEAC assay. It has been found that compounds 8 and 9 with benzothiazole or phenol fragments are more active in DPPH test. The presence of electron-rich moieties in the catecholate ligand makes complexes 5 and 7-9 more reactive to ABTS radical cation. The value of CUPRACTEAC for organogermanium(IV) catecholates varies from 0.23 to 1.45. The effect of compounds 1-9 in the process of lipid peroxidation of rat liver (Wistar) homogenate was determined in vitro. It was found that most compounds are characterized by pronounced antioxidant activity. A feature of complexes 1, 3, and 5-9 is the intensification of the antioxidant action with the incubation time. In the presence of additives of complexes 3, 5, 6, and 8, an induction period was observed during the process of lipid peroxidation.

The antimicrobial effects of silver nanoparticles obtained through the royal jelly on the yeasts Candida guilliermondii NP-4

The effect of silver nanoparticles (Ag NPs) obtained in the presence of royal jelly (RJ) on the growth of yeast Candida guilliermondii NP-4, on the total and H+-ATPase activity, as well as lipid peroxidation process and antioxidant enzymes (superoxide dismutase (SOD), catalase) activity was studied. It has been shown that RJ-mediated Ag NPs have a fungicide and fungistatic effects at the concentrations of 5.4 µg mL−1 and 27 µg mL−1, respectively. Under the influence of RJ-mediated Ag NPs, a decrease in total and H+-ATPase activity in yeast homogenates by ~ 90% and ~ 80% was observed, respectively. In yeast mitochondria total and H+-ATPase activity depression was detected by ~ 80% and ~ 90%, respectively. The amount of malondialdehyde in the Ag NPs exposed yeast homogenate increased ~ 60%, the catalase activity increased ~ 70%, and the SOD activity—~ 30%. The obtained data indicate that the use of RJ-mediated Ag NPs have a diverse range of influence on yeast cells. This approach may be important in the field of biomedical research aimed at evaluating the development of oxidative stress in cells. It may also contribute to a more comprehensive understanding of antimicrobial properties of RJ-mediated Ag NPs and help control the proliferation of pathogenic fungi.

Effect of interval hypoxytherapy on the immune status of hypertensive patients

In recent years, the role of sluggish nonspecific inflammation in the pathogenesis of hypertension has been proven. Oxidative stress that develops in hypertension leads to damage of endothelial glycocalyx with impaired barrier and adaptive functions of endothelium. Activation of transcription factor NF-kB leads to increased synthesis of free oxygen radicals, adhesion molecules (VCAM-1, ICAM-1, P-selectin, E-selectin) and proinflammatory cytokines (TNFα, IL-1, IL-6), triggering the inflammatory process in the endothelium. Modern antihypertensive drugs, affecting various pathogenetic mechanisms of arterial hypertension development, do not fully affect the immune component of arterial hypertension. Therefore, the search for various methods affecting the immunologic reactivity of hypertensive patients remains relevant in our time. The aim of the study was to reveal the effect of interval hypoxytherapy on the state of immunologic reactivity of patients with hypertension stage I. One hundred seventy male patients of 30-45 years old (mean age 38.36±1.64 years) with hypertension stage I (n = 170) who underwent combined treatment including drug therapy and normobaric interval hypoxic therapy in hypoxia-normoxia mode (oxygen content in hypoxic gas mixture was 20.9%) were examined. Indices of redox status and immunologic reactivity before and after interval hypoxytherapy were studied. Having a significant antioxidant effect, interval hypoxytherapy led to the subsidence of oxidative stress, which was indicated by an increase in the activity of superoxide dismutase and glutathione peroxidase in blood erythrocytes and a decrease in the content of malonic dialdehyde in blood as a result of a decrease in the generation of free oxygen radicals and suppression of lipid peroxidation processes. Interval hypoxytherapy resulted in a statistically significant increase in the initially decreased content of CD3+T lymphocytes (p 0.05), CD3+CD4+T lymphocytes (p 0.02), CD3+CD8+T lymphocytes (p 0.02). Initially increased number of B-lymphocytes CD19+, CD16+ lymphocytes, CD95+ lymphocytes significantly decreased. An important result of interval hypoxytherapy was a pronounced anti-inflammatory effect: statistically significant decrease in the content of pro-inflammatory interleukins IL-1β (p 0.02), IL-6 (p 0.01) and increase in the content of anti-inflammatory cytokines IL-4 (p 0.005) and IL-10 (p 0.005), which led to the subsidence of sluggish nonspecific inflammation. Suppression of oxidative stress and normalization of immunological reactivity of hypertensive patients after interval hypoxytherapy led to the subsidence of sluggish nonspecific inflammation, reduction of endothelial dysfunction and restoration of the structure and tone of the vascular wall with a decrease in blood pressure and improvement of the clinical course of hypertension.

The Possible Protective Role of N-acetylcysteine against Testicular Toxicity Induced by Paracetamol Overdose in Adult Male Rats

Many substances, even medicines with proven therapeutic benefits, can harm cells by metabolically activating them into extremely reactive substances. Paracetamol is one of the most widely used over-the-counter analgesics. This study examines the harmful effects of paracetamol on the lipid peroxidation process in testes homogenates as well as enzymatic and non-enzymatic antioxidant activities. Also, examine the effects on male hormones and sperm count. The study also assesses if N-acetylcysteine protects against testicular damage induced by paracetamol excess. Forty mature male albino rats were created. Group 1 as a control, Group 2 paracetamol (650 mg/kg), Group 3 NAC (150 mg/kg), and Group 4 both paracetamol and NAC. Samples of blood and testicles were taken after 15 days to measure sperm and testicular biochemistry. Testicular tissues had considerably higher amounts of MDA and H2O2. SOD, GSH, and CAT levels significantly decreased. FSH and LH rise. On the other hand, testosterone levels decrease following paracetamol exposure. The administration of NAC generated changes in testosterone levels, FSH, LH, and antioxidant enzymes. The sperm morphology showed an increase in abnormalities but a significant decrease in motility and count. NAC effectively lowers the toxicity of paracetamol to the testicles while restoring biomarkers associated with normal testicular function.

Analytical Method Development and Validation for Butylated Hydroxy Toluene by using UV- Visible Spectrophotometric Method

Upon utilizing the Prediction Activity Spectra of Substances (PASS) program, computer-aided predictions were conducted to assess the antioxidant activities. Compounds 1, 3, 4, and 5 underwent evaluation using 1,1-diphenyl-2- picrylhydrazyl (DPPH) and lipid peroxidation assays to confirm the predictions obtained from the PASS program. Notably, compounds 3 and 5 exhibited higher inhibition of the DPPH stable free radical at 10 M compared to the widely recognized standard antioxidant, butylated hydroxytoluene (BHT). Of particular interest, compound 5 demonstrated significant in vitro inhibition of Fe-induced lipid peroxidation in the lipid-rich medium of essential egg yolk (83.99%, IC50 16.07 ± 3.51 μM/mL) in contrast to α-tocopherol (α-ΤΟΗ, 84.6%, IC50 5.6 ± 1.09 μM/mL). Furthermore, the drug-likeness of these BHT analogues was assessed based on Lipinski's "rule-of-five" (RO5), revealing a violation of one parameter (Log P > 5) despite their solubility in protic solvents. The predictive polar surface area (PSA) and absorption percentage (% ABS) data imply a potential capacity for cell membrane penetration. Consequently, these new multipotent antioxidants (MPAOs) hold promise as effective agents for addressing oxidative stress and lipid peroxidation processes.

Bio-Inspired Carbon Dots as Malondialdehyde Indicator for Real-Time Visualization of Lipid Peroxidation in Depression.

Brain lipidic peroxidation is closely associated with the pathophysiology of various psychiatric diseases including depression. Malondialdehyde (MDA), a reactive aldehyde produced in lipid region, serves as a crucial biomarker for lipid peroxidation. However, techniques enabling real-time detection of MDA are still lacking due to the inherent trade-off between recognition dynamics and robustness. Inspired by the structure of phospholipid bilayers, amphiphilic carbon dots named as CG-CDs targeted to cell membrane are designed for real-time monitoring of MDA fluctuations. The design principle relies on the synergy of dynamic hydrogen bonding recognition and cell membrane targetability. The latter facilitates the insertion of CG-CDs into lipid regions and provides a hydrophobic environment to stabilize the labile hydrogen bonding between CG-CDs and MDA. As a result, recognition robustness and dynamics are simultaneously achieved for CG-CDs/MDA, allowing for in situ visualization of MDA kinetics in cell membrane due to the instant response (<5 s), high sensitivity (9-fold fluorescence enhancement), intrinsic reversibility (fluorescence on/off), and superior selectivity. Subsequently, CG-CDs are explored to visualize nerve cell membrane impairment in depression models of living cells and zebrafish, unveiling the extensive heterogeneity of the lipid peroxidation process and indicating a positive correlation between MDA levels and depression.

Prevention of immobilization stress-induced lipid peroxidation processes and antioxidant protection disorders in the development of experimental periodontitis

Prevention of immobilization stress-induced lipid peroxidation processes and antioxidant protection disorders in the development of experimental periodontitis