Lipid Peroxidation Products Research Articles

FSP1 Acts in Parallel with GPX4 to Inhibit Ferroptosis in COPD.

Glutathione peroxidase 4 (GPX4) has recently been reported to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Ferroptosis suppressor protein-1 (FSP1) is a protein that defends against ferroptosis in parallel with GPX4, but its role in the pathogenesis of COPD remains unexplored, and further research is needed. Normal and COPD lung tissues were obtained from lobectomy and lung transplant specimens, respectively. FSP1-overexpressing mice were established by monthly transfection with AAV9-FSP1 through modified intranasal administration. The expression of FSP1, GPX4, and prostaglandin-endoperoxide synthase 2 (PTGS2) was measured by Western blotting, immunohistochemistry and other methods. The correlation between FSP1 and ferroptosis and the role of FSP1 in COPD were explored by screening the expression of ferroptosis-related genes in a COPD cell model after the inhibition and overexpression of FSP1. We then explored the underlying mechanism of low FSP1 expression in patients with COPD in vitro by methylated RNA immunoprecipitation (MeRIP)-qPCR. We found that cigarette smoke exposure can lead to an increase in lipid peroxide production and ultimately ferroptosis, which is negatively regulated by FSP1 activity. FSP1 overexpression can prevent ferroptosis and alleviate emphysema. Next, we found that decreased FSP1 expression was caused by increased m6A modification of FSP1 mRNA. Moreover, the level of FSP1 decreased in a YTHDF2-dependent manner. These results indicate that METTL3-induced FSP1 mRNA methylation leading to low FSP1 expression is a potential therapeutic target for COPD. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Indices of carbohydrate metabolism and antioxidant system state during germination of aged wheat and triticale seeds treated with H(2)S donor

Hydrogen sulfide is a gasotransmitter molecule involved in the realization of many functions of the plant organism, including seed germination. Aging of seeds is shown to be accompanied by oxidative stress and reduced germination. The effect of exogenous hydrogen sulfide on the germination of aged cereal seeds has not been studied. The aim of the work was to estimate the effect of priming with NaHS as an H2S donor on wheat and triticale seeds previously subjected to natural aging. Seeds of winter wheat (Triticum aestivum) and winter ×Triticosecale were stored indoors for 4 years at fluctuating temperature and humidity. Aged seeds were treated with 0.2-5 mM NaHS solution for 3 h and germinated in Petri dishes for 3 days. The hydropriming­ treatment was used as a control. Amylase activity in grains, the biomass of shoots and roots, the content of total sugars, H2O2, lipid peroxidation products and anthocyanin, and the activity of antioxidant enzymes in seedlings were determined. It was shown that after the treatment with H2S donor, the activities of catalase and guaiacol peroxidase, as well as the content of anthocyanins were increased only in triticale seedlings. Nevertheless, treatment of seeds of both cereal species was followed by enhanced growth of shoots and roots, increase in amylase and superoxide dismutase activities, decrease in H2O2 and MDA contents, and elevated accumulation of sugars in shoots. It is concluded that the increase in germination of aged cereal seeds under the influence of H2S donor is caused by increased mobilization of reserve carbohydrates and modulation of antioxidant system activity. Such treatment can be considered as an effective tool to improve seedling growth. Keywords: amylase, antioxidant system, hydrogen sulfide, oxidative stress, seeds aging, total sugar, Triticosecale, Triticum aestivum

Upregulation of PRRX2 by silencing Marveld3 as a protective mechanism against radiation-induced ferroptosis in skin cells.

Radiation-induced skin injury (RISI) represents a significant complication in patients receiving radiotherapy and individuals exposed to nuclear accidents, characterized by a protracted wound-healing process relative to injuries from other etiologies. Current preventive and management approaches remain inadequate. Consequently, investigating efficacious intervention strategies that target the disease's progression characteristics holds significant practical importance. Small interfering RNA (siRNA) and overexpression plasmid were used to modulate the expression of Marvel domain containing 3 (Marveld3) and paired related homeobox 2 (PRRX2). Protein and mRNA levels were estimated by Western Blot and real-time PCR, respectively. Intracellular levels of Malondialdehyde (MDA), a terminal product of lipid peroxidation, were measured following the manufacturer's protocol for MDA assay kit. Similarly, intracellular levels of ferrous iron (Fe2+) and reactive oxygen species (ROS) were determined using their respective assay kits. Lipid peroxidation status within the cells was evaluated via BODIPY staining. Immunohistochemistry was conducted to ascertain the expression of PRRX2 in skin tissues collected at various time points following irradiation of rats. The H-score method was used to evaluate the percentage of positively stained cells and staining intensity. RNA sequencing, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted by OE Biotech Company. In this study, our findings indicated that Marveld3 suppression could effectively inhibit lipid peroxidation levels in irradiated skin cells, concomitantly reducing intracellular Fe2+ content. Additionally, the silencing of Marveld3 effectively abrogated the impact of a ferroptosis agonist on cellular viability, resulting in the upregulation of 66 and 178 genes, as well as the downregulation of 188 and 31 genes in irradiated HaCaT and WS1 cells, respectively. Among the differentially expressed genes, the PRRX2 which was found to be involved in the process of ferroptosis, exhibited statistically significant upregulation. And the upregulation of PRRX2 expression may attenuate radiation-induced lipid peroxidation in skin cells, thereby functioning as a potential stress-responsive mechanism to counteract radiation effects. This study elucidates the role of Marveld3 in radiation-induced ferroptosis in skin cells. Inhibition of Marveld3 led to the upregulation of PRRX2, which subsequently resulted in a reduction of Fe2+ and ROS levels, as well as the suppression of lipid peroxidation. These effects collectively mitigated the occurrence of ferroptosis.

Metabolic pathways for removing reactive aldehydes are diminished in the skeletal muscle during heart failure.

Muscle wasting is a serious complication in heart failure patients. Oxidative stress and inflammation are implicated in the pathogenesis of muscle wasting. Oxidative stress leads to the formation of toxic lipid peroxidation products, such as 4-hydroxy-2-nonenal (HNE), which covalently bind with proteins and DNA and activate atrophic pathways. Whether the formation of lipid peroxidation products and metabolic pathways that remove these toxic products are affected during heart failure-associated skeletal muscle wasting has never been studied. Male C57BL/6J mice were subjected to sham and transverse aortic constriction (TAC) surgeries for 4, 8 or 14weeks. Different skeletal muscle beds were weighed, and the total cross-sectional area of the gastrocnemius muscle was measured via immunohistochemistry. Muscle function and muscle stiffness were measured by a grip strength meter and atomic force microscope, respectively. Atrophic and inflammatory marker levels were measured via qRT‒PCR. The levels of acrolein and HNE-protein adducts, aldehyde-removing enzymes, the histidyl dipeptide-synthesizing enzyme carnosine synthase (CARNS), and amino acid transporters in the gastrocnemius muscle were measured via Western blotting and qRT‒PCR. Histidyl dipeptides and histidyl dipeptide aldehyde conjugates in theGastrocnemius and soleus muscles were analyzed by LC/MS-MS. Body weight, gastrocnemius muscle and soleus muscle weights and the total cross-sectional area of the gastrocnemius musclewere decreased after 14weeks of TAC. Heart weight, cardiac function, grip strength and muscle stiffness were decreased in the TAC-operated mice. Expression of the atrophic and inflammatory markers Atrogin1 and TNF-α, respectively, was increased ~ 1.5-2fold in the gastrocnemius muscle after 14weeks of TAC (p < 0.05 and p = 0.004 vs sham). The formation of HNE and acrolein protein adducts was increased, and the expression of the aldehyde-removing enzyme aldehyde dehydrogenase (ALDH2) was decreased in the gastrocnemius muscle of TAC mice. Carnosine (sham: 5.76 ± 1.3 vs TAC: 4.72 ± 0.7nmol/mg tissue, p = 0.04) and total histidyl dipeptide levels (carnosine and anserine; sham: 11.97 ± 1.5 vs TAC: 10.13 ± 1.4nmol/mg tissue, p < 0.05) were decreased in the gastrocnemius muscle of TAC mice. Depletion of histidyl dipeptides diminished the aldehyde removal capacity of the atrophic gastrocnemius muscle. Furthermore, CARNS and TAUT protein expression were decreased in the atrophic gastrocnemius muscle. Our data reveals that reduced expression of ALDH2 and depletion of histidyl dipeptides in the gastrocnemius muscle during heart failure leads to the accumulation of toxic aldehydes and might contribute to muscle wasting.

Activity of photosynthetic pigments and the antioxidant system in sunflower under drought stress

Background. The study is of particular importance in view of the increasing pace of global climate aridization. The article highlights the results of an experiment on the effect of drought on the physiological status of seedlings of cv. ‘Poseidon 625’ representing an important food crop – sunflower (Helianthus annuus L.). Materials and methods. The experiment included a group of control samples grown with sufficient moisture and four impact groups subjected to osmotic stress. The intensity of accumulation of lipid peroxidation products (LPP) was measured by the reaction of malondialdehyde (MDA) with thiobarbeturic acid; catalase activity was assessed by a photocolorimetric method based on the interaction between hydrogen peroxide and potassium iodide; the content of pigments (Chl a, Chl b, Сar) was calculated spectrophotometrically in acetone extract. Results. The degree of POL accumulation in the impact groups of the experiment was found to be many times higher than the values in the control samples, which was confirmed by a rapid increase in the MDA concentration in response to a growing water shortage. The accumulation of oxygen free radicals triggered the mechanisms of antioxidant protection of seedlings by synthesizing catalase, the concentration of which increased proportionally to the accumulation of POL. At the same time, the rapid accumulation of POL in the absence of irrigation and under osmotic stress of 3 and 5 atm led to a suppression of low-molecular-weight components of protection (carotenoids) and activation of their synthesis only when critical values of osmotic stress were reached. Conclusion. As a result of the experiment, catalase was identified as the main component of antioxidant protection in sunflower seedlings. Due to the activation of its synthesis, the concentrations of Chl a and Chl b decreased, attesting to the activation of the mechanisms protecting the photosynthetic activity in seedlings, and their antioxidant status.

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 &lt; 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 &lt; 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.

Lipid peroxidation products induce carbonyl stress, mitochondrial dysfunction, and cellular senescence in human and murine cells.

Lipid enals are electrophilic products of lipid peroxidation that induce genotoxic and proteotoxic stress by covalent modification of DNA and proteins, respectively. As lipid enals accumulate to substantial amounts in visceral adipose during obesity and aging, we hypothesized that biogenic lipid enals may represent an endogenously generated, and therefore physiologically relevant, senescence inducers. To that end, we identified that 4-hydroxynonenal (4-HNE), 4-hydroxyhexenal (4-HHE) or 4-oxo-2-nonenal (4-ONE) initiate the cellular senescence program of IMR90 fibroblasts and murine adipose stem cells. In such cells, lipid enals induced accumulation of γH2AX foci, increased p53 signaling, enhanced expression of p21Cip1, and upregulated the expression and secretion of numerous cytokines, chemokines, and regulatory factors independently from NF-κB activation. Concomitantly, lipid enal treatment resulted in covalent modification of mitochondrial proteins, reduced mitochondrial spare respiratory capacity, altered nucleotide pools, and increased the phosphorylation of AMP kinase. Lipid-induced senescent cells upregulated BCL2L1 (Bcl-xL) and BCL2L2 (Bcl-w). and were resistant to apoptosis while pharmacologic inhibition of BAX/BAK macropores attenuated lipid-induced senescence. Insitu, the 4-HNE scavenger L-carnosine ameliorated the development of the cellular senescence, while in visceral fat of obese C57BL/6J mice, L-carnosine reduced the abundance of 4-HNE-modified proteins and blunted the expression of senescence biomarkers CDKN1A (p21Cip1), PLAUR, BCL2L1, and BCL2L2. Taken together, the results suggest that lipid enals are endogenous regulators of cellular senescence and that biogenic lipid-induced senescence (BLIS) may represent a mechanistic link between oxidative stress and age-dependent pathologies.

Deubiquitylase USP52 Promotes Bladder Cancer Progression by Modulating Ferroptosis through Stabilizing SLC7A11/xCT.

Bladder cancer (BLCA) is a prevalent cancer with high case-fatality rates and a substantial economic burden worldwide. Understanding its molecular underpinnings to guide clinical management is crucial. Ferroptosis, a recently described non-apoptotic form of cell death, is initiated by the lethal accumulation of iron-dependent lipid peroxidation products. Despite growing interest, the roles and vulnerabilities determining ferroptosis sensitivity in BLCA remain unclear. Re-analysis of single-cell RNA data reveals a decrease in high-ferroptosis cancer cells as BLCA advances. USP52/PAN2 is identified as a key regulator of ferroptosis in BLCA through an unbiased siRNA screen targeting 96 deubiquitylases (DUBs). Functionally, USP52 depletion impedes glutathione (GSH) synthesis by promoting xCT protein degradation, increasing lipid peroxidation and ferroptosis susceptibility, thus suppressing BLCA progression. Mechanistically, USP52 interacts with xCT and enzymatically cleaves the K48-conjugated ubiquitin chains at K4 and K12, enhancing its protein stability. Clinical BLCA samples demonstrate a positive correlation between USP52 and xCT expression, with high USP52 levels associated with aggressive disease progression and poor prognosis. In vivo, USP52 depletion combined with ferroptosis triggers imidazole ketone Erastin (IKE) synergistically restrains BLCA progression by inducing ferroptosis. These findings elucidate the role of the USP52-xCT axis in BLCA and highlight the therapeutic potential of targeting USP52 and ferroptosis inducers in BLCA.

The Role of Arginase and some Parameters in Diabetic Type 2 Patients with and without Retinopathy

Background: Oxidative stress plays a major role in the pathogenesis of diabetes mellitus by damaging cellular organelles and enzymes in blood such as arginase1, insulin and glutathione s-transferase; increasing lipid peroxidation such as malondialdehyde and increasing insulin resistance which can lead to diabetic complications such as diabetic retinopathy. Objectives: To explore the relationship of oxidative stress to the development of diabetic retinopathy by measuring the levels of Arginase1, the activity of glutathione s-transferase enzyme, and the levels of malondialdehyde as a secondary product of lipid peroxidation (biomarker for oxidative stress). Patients and MethodsThis study was conducted from November 2022 to January 2023 at the Ibn Al-Haitham Teaching Eye Hospital in Baghdad, the University of Baghdad / Department of Chemistry and the National Diabetes Centre for Treatment and Research at Al-Mustansyrriah University. This study was conducted on 120 subjects distributed as follows: 40 non-diabetic obese controls, 40 type 2 diabetics with no retinopathy, and 40 type 2 diabetic retinopathy patients, between 30 and 65 years of age. All groups were subjected to tests: measuring fasting blood glucose (FBG), HbA1c, lipid profile (cholesterol, triglycerides, HDL- cholesterol, LDL- cholesterol, and VLDL cholesterol), serum total arginase1, malondialdehyde glutathione s -transferase, body mass index (BMI), and waist-to-hip ratio. Results: Mean arginase1 levels were significantly higher in diabetic patients than in diabetic retinopathy and control groups (p ≤ 0.05). The mean xidative stress marker malondialdehyde concentration was significantly higher in diabetic retinopathy patients than in type 2 diabetics and the control group (P ≤ 0.05). The mean glutathione s-transferase activity in diabetic retinopathy patients was significantly higher than in the control group and type 2 diabetics (P ≤ 0.05). Conclusion: There is a relationship between oxidative stress and the development of diabetic retinopathy, where the levels of arginase1 and malondialdehyde increased and the activity of glutathione s –transferase enzyme increased as a result of oxidative stress and inflammation associated with complications of type 2 diabetes.

A coumarin derivative C7 exhibits antiviral activity against WSSV by reducing phosphatidylcholine content in shrimp

The white spot syndrome virus (WSSV) causes white spot disease (WSD), a severe condition in crustacean aquaculture, leading to significant economic losses. Our previous study demonstrated that C7 is an effective therapeutic agent against WSSV infection in aquaculture. It specifically blocked viral horizontal transmission and reduced shrimp mortality in a dose- and time-dependent manner. Here, we report the potential antiviral mechanism of C7 in shrimp. C7 regulated abnormal glycerophospholipid metabolism caused by WSSV and inhibited phosphatidylcholine (PC) synthesis by more than twofold, potentially enhancing shrimp resistance to viral infection. As the primary phospholipid in the cell membrane, PC is one of the main reactants in lipid peroxidation. Our results indicated that C7 significantly reduced the levels of lipid peroxidation products 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) induced by WSSV, whereas PC had the opposite effect. Accumulation of lipid peroxidation products inhibits stimulator of interferon genes (STING) signaling. Further evidence showed that C7 promoted STING transport from the endoplasmic reticulum to the Golgi apparatus, significantly activating the expression of the shrimp interferon analogue Vago4 gene. In contrast, PC suppressed Vago4 expression. Our results demonstrated that C7 inhibited PC synthesis, reduced the degree of lipid peroxidation, promoted STING translocation, activated Vago4 expression, and ultimately exerted antiviral effects. Therefore, C7 exhibits immunoregulatory activity as a preventative agent for enhancing the innate immunity of shrimp, making it potentially useful for future immunomodulatory approaches.

Borna disease virus 1 induces ferroptosis, contributing to lethal encephalitis.

Borna disease virus 1 (BoDV-1) is a neurotropic RNA virus that has been linked to fatal BoDV-1 encephalitis (BVE) in humans. Ferroptosis represents a newly recognized kind of programmed cell death that marked by iron overload and lipid peroxidation. Various viral infections are closely related to ferroptosis. However, the link between BoDV-1 infection and ferroptosis, as well as its role in BVE pathogenesis, remains inadequately understood. Herein, we used primary rat cortical neurons, human microglial HMC3 cells, and Sprague‒Dawley rats as models. BoDV-1 infection induced ferroptosis, as ferroptosis characteristics were detected (iron overload, reactive oxygen species buildup, decreased antioxidant capacity, lipid peroxidation, and mitochondrial damage). Analysis via qRT-PCR and Western blot demonstrated that BoDV-1-induced ferroptosis was mediated through Nrf2/HO-1/SLC7a11/GPX4 antioxidant pathway suppression. Nrf2 downregulation was due to BoDV-1 infection promoting Nrf2 ubiquitination and degradation. Following BoDV-1-induced ferroptosis, the PTGS2/PGE2 signaling pathway was activated, and various intracellular lipid peroxidation products and damage-associated molecular patterns were released, contributing to BVE occurrence and progression. More importantly, inhibiting ferroptosis or the ubiquitin‒proteasome system effectively alleviated BVE. Collectively, these findings demonstrate the interaction between BoDV-1 infection and ferroptosis and reveal BoDV-1-induced ferroptosis as an underlying pathogenic mechanism of BVE.

Novel derivative of nicotinic acid ameliorates doxorubicin-induced cardiac injury via regulation of redox homeostasis

Introduction: Doxorubicin (DOX) is an anthracycline antibiotic with considerable significance in clinics as an anticancer agent, which is limited by its cardiotoxicity, though. A large number of possible therapeutic strategies for reducing cardiotoxicity with doxorubicin have been studied. However, none of them fully meets the requirements of clinical practice. The aim of the study: to evaluate the cardioprotective effects of a new original heterocyclic compound, a pyridine-3-carboxylic acid derivative potassium 5-hydroxynicotinate. Materials and Methods: Cardiac injury was induced by intraperitoneal administration of doxorubicin (DOX) at a dose of 20 mg/kg. After 48 hours, the parameters of left ventricular contractility and StTTI coefficient were assessed on isolated heart in the Langendorff system under the conditions of 480 beats per minute for 11 seconds. Additionally, specific markers of myocardial injury were determined. The lipid peroxidation products and SOD activity were measured as well to challenge whether the compound is able to reduce oxidative stress. Results: The study showed that pretreatment by potassium 5-hydroxynicotinate (35 mg/kg, 48 h) attenuated DOX-induced damage, resulting in a significant decrease in the StТТI coefficient to 3.3 values and in the restoration of the antioxidant activity of enzymes. Conclusion: The obtained data totally demonstrate the protective effects of potassium 5-hydroxynicotinate in DOX-induced cardiomyopathy. A significant role in potassium 5-hydroxynicotinate-mediated cardioprotection is, apparently, related to the reduction of oxidative stress and down-regulation of the level of intracellular calcium.

In-silico analysis of ethanol peel extract of Citrus sinensis on mercury chloride-induced prefrontal cortex damage in Wistar rat

This study evaluated the effect of ethanolic extract of Citrus sinensis peel on mercury chloride-induced changes in the prefrontal cortex of adult Wistar rats. Twenty-five Wistar rats were purchased and divided into five groups containing five animals in each group. Group 1 was administered with distilled water, Group 2, Group 3, Group 4, and Group 5 were administered with 5 mg/kg of mercury chloride only, 5 mg/kg of mercury chloride and 140 mg/kg Silymarin, 5 mg/kg mercury chloride and 1000 mg/kg of ethanoic extract of orange peel, and 5 mg/kg mercury chloride and 1500 mg/kg of ethanoic extract of orange peel. All administration was done orally and the administration lasted for 14 days. The animals were sacrificed humanely using 75 mg/kg ketamine intraperitoneally and prefrontal was dissected out. Part was homogenized in 0.1M phosphate buffered saline for the estimation of superoxide dismutase (SOD), and catalase (CAT) activities, and Malondialdehyde (MDA) level and the other part was fixed by immersion in 10 neutral buffered formal-saline for histological evaluation. The chemical structure of sixteen compounds from Citrus sinensis peel obtained from GC-MS analysis reported in the literature were retrieved from the PubChem compound database and the crystal structure of human peroxisome proliferator- activated receptor gamma (PPARγ; PDB:ID: 2P4Y) reported to increase the expression of catalase gene, human extracellular copper-zinc superoxide dismutase enzyme (PDB ID: 2JLP) and mammalian 15-lipoxygenase - 1 enzyme (PDB ID: 2P0M) responsible for the production of lipid peroxidation were retrieved from the PDB database. Ligands and protein preparation, docking and MM-GBSA relative binding free energy calculation were done in Maestro 2023.1. Data obtained was analyzed using the IBM SPSS (version 25) using one-way ANOVA and p-value &lt; 0.05 was considered statistically significant. The results indicate that the MDA level in control Group(13.29±1.183 μmol) is statistically significantly lower compared to the Group 2 (21.88±1.96 μmol), group 3 (27.44±3.52 μmol), Group 4 (22.20±1.16 μmol) and Group 5 (25.40±3.13 μmol). No statistically significant difference was observed in SOD activity. The CAT activities in control group (53.51±6.83 nmol/ml) was statistically significantly lower compared to the group 2 (26.21±3.70 nmol/ml), Group 3 (27.17±5.32 nmol/ml), Group 4 (25.30±4.24 nmol/ml) and Group5 (26.59±4.22 nmol/ml).The present study suggests, ethanolic extract of Citrus sinensis peel have protective effects on mercury-induced changes in prelimbic part of the prefrontal cortex of adult Wistar rats.

Endogenous γ-Aminobutyric Acid Accumulation Enhances Salinity Tolerance in Rice

Rice is an important food crop worldwide but is usually susceptible to saline stress. When grown on soil with excessive salt, rice plants experience osmotic, ionic, and oxidative stresses that adversely affect growth performance. γ-Aminobutyric acid (GABA) is a nonproteinogenic amino acid that plays an important role in the metabolic activities of organisms. Glutamate decarboxylase (GAD) is the rate-limiting enzyme in GABA metabolism. Here, we genetically modified rice GAD by overexpression or CRISPR-mediated genome editing. These lines, named gad3-ox1 and gad3-ox2 or gad1/3-ko, were used to explore the effects of endogenous GABA accumulation on salt tolerance in rice. Both the gad3-ox1 and gad3-ox2 lines exhibited significant accumulation of the GABA content, whereas the gad1/3-ko line presented a reduced GABA content in vivo. Notably, the two overexpression lines were markedly resistant to salt stress compared with the wild-type and knockout lines. Furthermore, our results demonstrated that endogenous GABA accumulation in the gad3-ox1 and gad3-ox2 lines increased the contents of antioxidant substances and osmotic regulators, decreased the content of membrane lipid peroxidation products and the Na+ content, and resulted in strong tolerance to salt stress. Together, these data provide a theoretical basis for cultivating rice varieties with strong salt tolerance.

Comparative Analysis of Oxidative Metabolism in Liver in Different Experimental Models of Hypothyroidism: Low Iodine Diet and Anti-Thyroid drug (Methimazole)

Objectives: On the concept of oxidative stress in hypothyroidism, which still remains ambiguous and controversial, the article emphasizes the issue of the impact of the experimental conditions on the validity of the data obtained in different methods of modeling thyroid dysfunction. Materials and Methods: Experiments were conducted on 112 white nonlinear male rats. Thyroid hormones and biomarkers of oxidative metabolism in the liver tissue were determined in rats kept for 3 months on a low-iodine diet (LID) and in rats with methimazole (MMI)-induced hypothyroidism (2,5 mg/100 g of body weight for 3 weeks). Results: In LID-rats (n=96) total serum T4 amounted 43, total T3 in liver tissue - 73% of the level found in euthyroid animal, p=0.0121 and p=0.0051, respectively), whereas in MMI-rats (n=96) both total and free serum T4 were 67% of control (p=0.0002 for both total and free T4). In LID-rats cytochrome oxidase (CcOX) activity in liver tissue was 68.5, concentration of malondialdehyde (MDA) - 58% of euthyroids (p value - 0.0202 and 0.0127, respectively), while protein carbonyls (PC) level was 116% of the control (p=0.0411). In MMI-rats liver malate dehydrogenase (MDH) activity decreased up to 70.9, but succinate dehydrogenase (SDH) activity and MDA concentration increased up to 163.6 and 154% of the level in euthyroid animals respectively (p˂0.05). Conclusion: LID-model led to the more pronounced inhibition of thyroid function, than that the MMI-hypothyroidism model used. LID-model was accompanied by a decrease in the intensity of oxidative metabolism in liver tissue, whereas MMI-hypothyroidism - by activation of the succinate oxidation pathway and an increase in the concentration of secondary lipid peroxidation products in the liver of experimental animals. The results suggest that the conflicting data obtained from studies of oxidative metabolism in hypothyroidism, among other assumptions, may be due to the different approaches used by researchers to model thyroid dysfunction.

SS-31 modification alleviates ferroptosis induced by superparamagnetic iron oxide nanoparticles in hypoxia/reoxygenation cardiomyocytes

Superparamagnetic iron oxide nanoparticles (SPION) are widely used in cardiovascular applications. However, their potential to induce ferroptosis in myocardial cells post-ischemia-reperfusion hinders clinical adoption. We investigated the mechanisms behind SPION-induced cytotoxicity in myocardial cells and explored whether co-loading SPION with SS-31 (a kind of mitochondrial-targeted antioxidant peptide) could counteract this toxicity.To create SPION@SS-31, SS-31 was physically adsorbed onto SPION. To study the dose- and time-dependent cytotoxic effects and assess the influence of SS-31 on reducing SPION-induced damage, hypoxia/reoxygenation(H/R) H9C2 cells were treated with either SPION or SPION@SS-31. We examined the relationship between SPION and ferroptosis by measuring mitochondrial ROS, mitochondrial membrane potential (MMP), lipid peroxidation products, ATP, GSH, GPX4, mitochondrial structure, nonheme iron content, cellular iron regulation, and typical ferroptosis markers.The findings showed that SPION induced concentration- and time-dependent toxicity, marked by a significant cell viability loss and an increase in LDH levels. In contrast, SPION@SS-31 produced results comparable to the H/R group, implying that SS-31 can notably reduce cell damage induced by SPION. SPION disrupted cellular iron homeostasis, with FtH and FtMt expression increased and reduced levels of FPN1 and ABCB8, which led to the overload of mitochondrial iron. This iron dysregulation damaged mitochondrial function and integrity, causing ATP depletion, MMP loss, and decreased GPX4 and GSH levels, accompanied by a burst of mitochondrial lipid peroxidation, ultimately resulting in ferroptosis in H/R cardiomyocytes. Notably, SS-31 significantly alleviated SPION-induced ferroptosis by decreasing mitochondrial MDA production and maintaining GSH and GPX4 levels, indicating its possibility to reverse SPION-induced cytotoxicity. The viability of H/R cells and cells treated with SPION and Fer-1 did not differ statistically, whereas cells exposed to SPION along with inhibitors like 3-MA, zVAD, or Nec-1 showed a substantial loss in viability, implying that ferroptosis is the primary mechanism behind SPION-induced myocardial toxicity.SPION triggers mitochondrial lipid peroxidation by causing overload of iron, leading to ferroptosis in H/R H9C2 cells. Mitochondria appear to be the primary target of SPION-induced toxic effects. SS-31 demonstrates potential in inhibiting this ferroptosis by acting as a mitochondria-targeted antioxidant, suggesting that the modification of mitochondria-targeted antioxidant peptides represents an innovative and practical approach to attenuate the myocardial toxicity associated with SPION.

Studying the composition and anti-radiation properties of sage (Salvia officinalis L.) in wheat seeds

Aim. The purpose of the research was to study the chemical composition, develop methods for obtaining an extract from the leaves of Salvia officinalis L. and study their anti-radiation properties of irradiated wheat seeds of the Guneshli variety. Methods. Using qualitative reactions and chromatography, the content of lipids, essential oils, diterpene acids, phenolic compounds, macro- and microelements in plants was determined. Wheat seeds were irradiated using a URI installation (K-25) at a dose rate of 13.4 rad/sec, at a dose of 200 Gy. The amount of chlorophyll pigments, carotenoids, and malondialdehyde was measured using a spectrophotometer. Chlorophyll fluorescence in leaves was determined using a MINI-PAM device. Results. According to the results of morphological and physiological-biochemical parameters of seedlings, 0.01 % and 0.001 % Salvia officinalis extract has a positive effect on growth and development, increases the maximum quantum yield of PS II and reduces the yield of lipid peroxidation product. Conclusions. It has been established that Salvia officinalis extract has a radioprotective effect and can be used as a radioprotector for some agricultural plants.

Response of Mycobacterium avium subsp. paratuberculosis isolates to reactive oxygen stress generated by treatment with copper ions

Copper (Cu) ions have been recognized for their efficacy in inactivating bacteria, including Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of Johne’s disease (JD) known for its resilience to unfavorable conditions. However, the response of MAP isolates isolated from cows to Cu exposure remains inadequately understood, as their responses may differ from those of laboratory-adapted reference strains. In this study, we examined the response of MAP isolates obtained from MAP-infected and affected cows to Cu ion treatment, comparing that with the response of the reference strain ATCC 19698 to the same treatment. Three MAP field isolates and the MAP reference strain were exposed to Cu ions, and their viability, protein/lipid damage, ROS production, and gene expression were evaluated in triplicate. Survival differed among isolates, with an isolate from a cow with clinical JD exhibiting increased tolerance to Cu exposure. While Cu treatment induced lipid peroxidation and ROS production across all isolates, genes associated with Cu detoxification and virulence were upregulated, particularly in the reference strain. Whole genome sequencing analysis revealed that, despite genomic similarities between field isolates and the reference strain ATCC 19698, there were differences regarding the presence/absence of genes related with certain virulence factors. Further research on Cu exposure with larger numbers of MAP isolates is needed to explain the stress-induced responses that influence MAP survival during natural infections and in challenging environments.

Novel insights on ecological responses of short- and long-chain perfluorocarboxylic acids in constructed wetlands coupled with modified basalt fiber bio-nest

The first investigation based on constructed wetlands coupled with modified basalt fiber bio-nest (MBF-CWs) was performed under exposure of short- and long-chain perfluorocarboxylic acids (PFCAs). In general, both perfluorooctanoic acid (PFOA) and perfluorobutanoic acid (PFBA) caused significant decline of chemical oxygen demand removal by 10.83 % and 4.73 %. However, only PFOA led to marked inhibition on total phosphorus removal by 12.51 % in whole duration. Suppression of removal performance resulted from side impacts on microbes by PFOA. For instance, activities of key enzymes like dehydrogenase (DHA), urease (URE), and phosphatase (PST) decreased by 52.77 %, 40.70 %, and 56.94 % in maximum under PFOA stress, while URE could alleviate over time. By contrast, distinct inhibition was only found on PST in later phases with PFBA exposure. PFCAs had adverse influence on alpha diversity of MBF-CWs, particularly long-chain PFOA. Both PFCAs caused enrichment of Proteobacteria, owing to increase of Gammaproteobacteria and Plasticicumulans by 22.04–35.79 % and 22.91–219.77 %. Nevertheless, some dominant phyla (like Bacteroidota and Acidobacteriota) and genera (like SC-I-84, Thauera, Subgroup_10, and Ellin6067) were only suppressed by PFOA, causing more hazards to microbial decontamination than PFBA did. As for plants, chlorophyll contents tend to decrease with PFOA treatment. Whereas, higher antioxidase activities and more lipid peroxidation products were uncovered in PFOA group, demonstrating more reactive oxygen species brought by long-chain PFCAs. This work offered new findings about ecological effects of MBF-CWs under PFCAs exposure, evaluating stability and sustainability of MBF-CW systems to treat sewage containing complex PFCAs.