Reactive nitrogen species act as the enhancers of glutathione pool in embryonic axes of apple seeds subjected to accelerated ageing.

MAIN CONCLUSION: Reactive nitrogen species mitigate the deteriorative effect of accelerated seed ageing by affecting the glutathione concentration and activities of GR and GPX-like. The treatment of apple (Malus domestica Borkh.) embryos isolated from accelerated aged seeds with nitric oxide-derived compounds increases their vigour and is linked to the alleviation of the negative effect of excessive oxidation processes. Reduced form of glutathione (GSH) is involved in the maintenance of redox potential. Glutathione peroxidase-like (GPX-like) uses GSH and converts it to oxidised form (GSSG), while glutathione reductase (GR) reduces GSSG into GSH. The aim of this work was to investigate the impact of the short-time NOx treatment of embryos isolated from apple seeds subjected to accelerated ageing on glutathione-related parameters. Apple seeds were subjected to accelerated ageing for 7, 14 or 21 days. Isolated embryos were shortly treated with NOx and cultured for 48 h. During ageing, in the axes of apple embryos, GSH and GSSG levels as well as half-cell reduction potential remained stable, while GR and GPX-like activities decreased. However, the positive effect of NOx in the vigour preservation of embryos isolated from prolonged aged seeds is linked to the increased total glutathione pool, and above all, higher GSH content. Moreover, NOx increased the level of transcripts encoding GPX-like and stimulated enzymatic activity. The obtained results indicate that high seed vigour related to the mode of action of NO and its derivatives is closely linked to the maintenance of higher GSH levels.

Enzymatic biomarkers of oxidative stress in patients with depressive disorders. A systematic review.

Oxidative stress (OS) results from the imbalance between the production of reactive oxygen species and the body's antioxidant mechanisms and is associated with various diseases, including depression. Antioxidants protect cells by neutralizing free radicals and include enzymatic components such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), and glutathione S-transferase (GST). The concentration of these biomarkers can quantify OS. This research aimed to gather available information published in the last ten years about the concentration of enzymatic OS biomarkers in samples from patients with depressive disorders. METHOD: A systematic review was conducted following the PRISMA guidelines, including original scientific articles that evaluated enzymatic OS biomarkers in participants with depressive disorders, using the keywords and boolean operators "superoxide dismutase" OR "catalase" OR "glutathione" AND "depress*" in the databases PubMed, SAGE Journals, DOAJ, Scielo, Dialnet, and Redalyc. RESULTS: The initial search showed 614 results, with only 28 articles meeting the selection criteria. It was observed that all evaluated oxidative stress enzymatic markers showed a significant increase or decrease in patients with depressive disorders, due to a wide variability in the depressive disorders studied, the type of biological sample analyzed, and the techniques used. CONCLUSION: There is evidence of the relationship between enzymatic OS biomarkers and depressive disorders, but additional studies are needed to clarify the nature of this relationship, particularly considering the different types of depressive disorders.

[Proinflammatory activity of monocytes and activity of glutathione-dependent enzymes in red blood cells in women with depressive conditions]. / Provospalitel'naya aktivnost' monotsitov i aktivnost' glutation-zavisimykh fermentov v eritrotsitakh krovi u zhenshchin s depressivnymi sostoyaniyami.

OBJECTIVE: To search for possible connections between the anti-inflammatory activity of monocytes (PAM) and the activity of glutathione metabolic enzymes: glutathione reductase (GR) and glutathione-S-transferase (GT) in patients with depressive states (DS) within various mental pathologies, as well as between the studied biological parameters and clinical condition of patients. MATERIAL AND METHODS: Sixty-one women, aged 18-56 years, with DC were examined before and after treatment. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depressive Symptom Rating Scale (HDRS-21). The control group included 23 women of the corresponding age without mental pathology. Biological parameters were assessed in the peripheral blood of patients and healthy people. RESULTS: Patients with a high level of PAM compared to the control (p<0.001) (subgroup 1, n=31) and with a low (at the control level) level (subgroup 2, n=30) were identified. In the subgroup 1, the values of GR and GT were significantly lower than in patients of subgroup 2 (p<0.05 and p<0.01, respectively). Negative correlations between the level of PAM before treatment and GR before and after treatment were revealed in patients who responded to treatment (r=-0.67; p=0.0041; r=-0.76; p=0.0001). CONCLUSION: The results may indicate the inverse relationship between the level of PAM and the activity of GR and GT, which are involved in the pathogenesis of DC, and can also serve as criteria for assessing the response of patients to treatment.

Unveiling silicon-mediated cadmium tolerance mechanisms in mungbean (Vigna radiata (L.) Wilczek): Integrative insights from gene expression, antioxidant responses, and metabolomics.

Cadmium (Cd), one of the most phytotoxic heavy metals, is a major contributor to yield losses in several crops. Silicon (Si) is recognized for its vital role in mitigating Cd toxicity, however, the specific mechanisms governing this mitigation process are still not fully understood. In the present study, the effect of Si supplementation on mungbean (Vigna radiata (L.) Wilczek) plants grown under Cd stress was investigated to unveil the intricate pathways defining Si derived stress tolerance. Non-invasive leaf imaging technique revealed improved growth, biomass, and photosynthetic efficiency in Si supplemented mungbean plants under Cd stress. Further, physiological and biochemical analysis revealed Si mediated increase in activity of glutathione reductase (GR), ascorbate peroxidase (APX), and catalase (CAT) enzymes involved in reactive oxygen species (ROS) metabolism leading to mitigation of cellular damage and oxidative stress. Untargeted metabolomic analysis using liquid chromatography coupled with mass spectrometry (LC-MS/MS) provided insights into Si mediated changes in metabolites and their respective pathways under Cd stress. Alteration in five different metabolic pathways with major changes in flavanols and flavonoids biosynthesis pathway which is essential for controlling plants antioxidant defense system and oxidative stress management were observed. The information reported here about the effects of Si on photosynthetic efficiency, antioxidant responses, and metabolic changes will be helpful in understanding the Si-mediated resistance to Cd stress in plants.

The assessment of glutathione, glutathione peroxidase, glutathione reductase, and oxidized glutathione in patients with periodontitis-A systematic review and meta-analysis.

OBJECTIVE: The present systematic review explored the involvement of enzymatic and nonenzymatic antioxidants in periodontitis, drawing from established literature. MATERIALS AND METHODS: The research approach encompassed an extensive electronic search from 2000 to 2023 across databases such as PubMed, Science Direct, and Wiley Online Library and cross-referencing using specific keywords. RESULTS: The initial literature exploration generated a total of 766 articles. After thoroughly examining the abstracts, 693 articles were excluded from consideration due to duplication and lack of relevance to the central research inquiry. Following that, 73 articles were left for in-depth evaluation. Following a qualitative assessment, 35 studies that satisfied the inclusion criteria were chosen, while 38 were removed for not meeting the necessary standards. Within this selection, a meta-analysis was conducted on 11 articles that provided consistent data for quantitative synthesis. Specifically, the analysis of glutathione (GSH) levels in serum samples revealed a standardized mean difference (SMD) of -5.552 µg/mL (CI 95%: -9.078 to -2.026; P-0.002). In contrast, the analysis of glutathione peroxidase (GPx) enzymes in gingival crevicular fluid (GCF) samples displayed an overall SMD of 2.918 ng/µL (CI 95%: 0.372-5.465; P-0.025), while salivary samples exhibited an overall SMD value of 0.709 U/l (95% CI: -1.907-3.325; P-0.596) which is of insignificant. CONCLUSION: The systematic review findings suggest a notable decrease in antioxidant enzymes across various systemic biological samples among patients with periodontitis, contrasting with the results from gingival tissue samples meta-analysis of GPx enzyme.

Antioxidant defenses and metabolic responses of Mytilus coruscus exposed to various concentrations of PAEs (phthalate esters).

Phthalate esters (PAEs), as a major plasticizer with multi-biotoxicity, are frequently detected in marine environments, and potentially affecting the survival of aquatic organisms. In the study, three typical PAEs (dimethyl phthalate [DMP], dibutyl phthalate [DBP] and di(2-ethylhexyl) phthalate [DEHP]) were selected to investigate the accumulation patterns and ecotoxicological effects on Mytilus coruscus (M. coruscus). In M. coruscus, the accumulation was DEHP>DBP>DMP, and the bioaccumulation in tissues was digestive glands>gills>gonads>muscles. Meanwhile, the activities of superoxide dismutase (SOD) and catalase (CAT) showed an activation-decrease-activation trend of stress, with more pronounced concentration effects. Glutathione reductase (GSH) activity was significantly increased, and its expression was more sensitive to be induced at an early stage. The metabolic profiles of the gonads, digestive glands and muscle tissues were significantly altered, and DEHP had a greater effect on the metabolic profiles of M. coruscus, with the strongest interference. PAEs stress for 7 d significantly altered the volatile components of M. coruscus, with potential implications for their nutritional value. This study provides a biochemical, metabolomic, and nutritional analysis of DMP, DBP, and DEHP toxic effects on M. coruscus from a multidimensional perspective, which provides support for ecotoxicological studies of PAEs on marine organisms. ENVIRONMENTAL IMPLICATION: Phthalate esters (PAEs), synthetic compounds from phthalic acid, are widespread in the environment, household products, aquatic plants, animals, and crops, posing a significant threat to human health. However, the majority of toxicological studies examining the effects of PAEs on aquatic organisms primarily focus on non-economic model organisms like algae and zebrafish. Relatively fewer studies have been conducted on marine organisms, particularly economically important shellfish. So, this study is innovative and necessary. This study provides a biochemical, metabolomic, and nutritional analysis of DMP, DBP, and DEHP toxic effects on mussels, and supports the ecotoxicology of PAEs on marine organisms.

Exploring potential inhibitors of acetylcholinesterase, lactate dehydrogenases, and glutathione reductase from Hagenia abyssinica (Bruce) J.F. Gmel. based on multi-target ultrafiltration-liquid chromatography-mass spectrometry and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Parasitic infections impose a significant burden on public health worldwide. European pharmacopoeia records and ethnopharmacological studies indicate that Hagenia abyssinica (Bruce) J.F. Gmel. has traditionally been used to treat a variety of parasitic infections, while the potential antiparasitic compounds remain ambiguous. AIM OF THE STUDY: Acetylcholinesterase (AChE), lactate dehydrogenases (LDH), and glutathione reductase (GR) are the key target enzymes in the survival of parasites. The aim of our work was to screen antiparasitic compounds targeting AChE, LDH, and GR from H. abyssinica. MATERIALS AND METHODS: Ultrafiltration-liquid chromatography-mass spectrometry (UF-LC-MS) combined with molecular docking was used in this study. Therein, the alamarBlue® and Ellman's methods were employed to reveal the antitrypanosomal effect and AChE inhibitory activity. Meanwhile, the UF-LC-MS was carried out to screen the potential active compounds from H. abyssinica. Subsequently, molecular docking was performed to evaluate the binding mechanisms of these active compounds with AChE, LDH, and GR. Finally, the AChE inhibitory activity of potential inhibitors was detected in vitro. RESULTS: H. abyssinica exhibited significant antitrypanosomal and AChE inhibitory activity. Corilagin, brevifolin carboxylic acid, brevifolin, quercetin, and methyl ellagic acid were recognized as potential AChE inhibitors by UF-LC-MS, while methyl brevifolin carboxylate was identified as AChE, LDH, and GR multi-target inhibitor, with binding degree ranged from 20.96% to 49.81%. Molecular docking showed that these potential inhibitors had a strong affinity with AChE, LDH, and GR, with binding energies ranging from -6.98 to -9.67 kcal/mol. These findings were further supported by the observation that corilagin, quercetin, brevifolin carboxylic acid, and methyl brevifolin carboxylate displayed significant AChE inhibitory activity compared with the positive control (gossypol, 0.42 ± 0.04 mM), with IC50 values of 0.15 ± 0.05, 0.56 ± 0.03, 0.99 ± 0.01, and 1.02 ± 0.03 mM, respectively. CONCLUSIONS: This study confirms the antiparasitic potential of H. abyssinica, supporting the traditional use of H. abyssinica in local ethnopharmacology to treat parasites. At the same time, corilagin, brevifolin carboxylic acid, brevifolin, quercetin, methyl ellagic acid, and methyl brevifolin carboxylate exert their anti-parasitic effects by inhibiting AChE, LDH, and GR, and they are expected to be natural lead compounds for the treatment of parasitic diseases.

Analysis of the interaction of antimalarial agents with Plasmodium falciparum glutathione reductase through molecular mechanical calculations.

CONTEXT: Malaria remains a significant global health challenge with emerging resistance to current treatments. Plasmodium falciparum glutathione reductase (PfGR) plays a critical role in the defense mechanisms of malaria parasites against oxidative stress. In this study, we investigate the potential of targeting PfGR with conventional antimalarials and dual drugs combining aminoquinoline derivatives with GR inhibitors, which reveal promising interactions between PfGR and studied drugs. The naphthoquinone Atovaquone demonstrated particularly high affinity and potential dual-mode binding with the enzyme active site and cavity. Furthermore, dual drugs exhibit enhanced binding affinity, suggesting their efficacy in inhibiting PfGR, where the aliphatic ester bond (linker) is essential for effective binding with the enzyme's active site. Overall, this research provides important insights into the interactions between antimalarial agents and PfGR and encourages further exploration of its role in the mechanisms of action of antimalarials, including dual drugs, to enhance antiparasitic efficacy. METHODS: The drugs were tested as PfGR potential inhibitors via molecular docking on AutoDock 4, which was performed based on the preoptimized structures in HF/3-21G-PCM level of theory on ORCA 5. Drug-receptor systems with the most promising binding affinities were then studied with a molecular dynamic's simulation on AMBER 16. The molecular dynamics simulations were performed with a 100 ns NPT ensemble employing GAFF2 forcefield in the temperature of 310 K, integration time step of 2 fs, and non-bond cutoff distance of 6.0 Å.

The elevated expression of serum glutathione reductase in hepatocellular carcinoma and its role in assessing the therapeutic efficacy and prognosis of transarterial chemoembolization.

BACKGROUND: Currently, there is a scarcity of reliable biomarkers that can accurately forecast the outcome and prognosis of transarterial chemoembolization (TACE). In this study, we assessed the diagnostic efficacy of serum glutathione reductase (GR) as a biomarker for hepatocellular carcinoma (HCC) and its practicality in predicting TACE treatment response. METHODS: The baseline positive rate and level of serum GR were analyzed and compared between HCC group and control group. Serum GR levels were assessed at three specific time points in 181 patients with unresectable HCC who underwent TACE (HCC-TACE). The correlation between serum GR levels and clinical pathological factors, tumor reactivity, and prognosis was investigated. The modified Response Evaluation Criteria in Solid Tumors (mRECIST) was utilized for assessing the treatment response to TACE. A nomogram for predicting the response to TACE treatment efficacy was developed. RESULTS: Serum GR demonstrated superior diagnostic performance in HCC patients. The baseline levels of serum GR were associated with the patient's age, tumor size, BCLC staging, and tumor thrombi of the portal vein (TTPV) (p < 0.05). Elevated baseline levels of serum GR were also identified as independent prognostic factors for predicting lower overall survival (OS) and shorter time to radiological progression (TTP) (p < 0.001). Moreover, it is worth noting that non-responders group exhibited a substantial increase in median GR level in the fourth week following TACE treatment (p < 0.0001), whereas the median GR level of responders group did not display a significant augmentation (p > 0.05). Lastly, the changes in serum GRt1-t3 were negatively correlated with TTP (p < 0.001). The nomogram developed to predict the risk of mRECIST responsiveness in patients with HCC-TACE demonstrated excellent discriminatory ability. CONCLUSION: Serum GR can serve as a valuable biomarker for the diagnosis of HCC and for predicting the therapeutic efficacy and prognosis of TACE treatment.

Heat Shock Protein HSP27 and the Status of the Glutathione System in Dexamethasone-Induced Apoptosis of Jurkat Tumor Cells.

We studied the effect of the HSP27 inhibitor, 5-(5-ethyl-2-hydroxy-4-methoxyphenyl)-4-(4-methoxyphenyl)-isoxazole, at a final concentration of 0.1 µM and/or the apoptosis inducer dexamethasone at a final concentration of 10 µM on the content of hydroxyl radical, reduced and oxidized glutathione, HSP27, activity of glutathione reductase, glutathione peroxidase, caspase-3, and the number of Annexin+ Jurkat tumor cells. The involvement of HSP27 in apoptosis of Jurkat tumor cells was demonstrated. Simultaneous exposure to the HSP27 inhibitor and dexamethasone resulted in an increase in the level of HSP27 against the background of developing oxidative stress (increase in the concentration of hydroxyl radicals and changes in the state of the glutathione system).

The effect of solarium light therapy on selected biological and biochemical parameters of peripheral blood in young and old horses.

The aim of the study was to assess the impact of solarium light therapy on selected biological and biochemical parameters of peripheral blood in recreational horses. The study involved 10 horses divided into two groups of young (aged 5 to 7 years) and old (aged 14 to 19 years) individuals. All animals participated in light therapy sessions every other day. Blood was sampled three times during the study: before the treatment, after five light sessions, and after ten light sessions. Morphological parameters, the activity of antioxidant enzymes, TAS values, and the levels of glutathione (GSH), vitamin D3, vitamin C, and malondialdehyde (MDA) were measured in the whole blood. Light therapy contributed to an increase in MCV, HDW, MCVr, CHr and MPV indices, and simultaneously a decrease in the basophil counts, MCHC, RDW and CHCMr indices in both groups of horses (p ≤ 0.05). At the same time reticulocytes fell in older whereas white blood cells and monocytes counts expanded in younger individuals. The treatment also increased the activity of glutathione reductase (GR) and glutathione peroxidase (GPx) in young but decreased the activity of mentioned enzymes in blood plasma of old horses. The total antioxidant status (TAS) of the blood plasma rose progressively, whereas GSH levels declined in all individuals. Moreover, vitamin D3 levels did not change, whereas vitamin C levels gradually decreased during the experiment. The therapy also helped to reduce levels of MDA in the blood plasma, especially of older horses (p ≤ 0.05). In turn, GPx and GR activities as well as MDA levels significantly declined, whereas GSH levels notably elevated in erythrocytes (p ≤ 0.05). Solarium light therapy appears to have a beneficial impact on the morphological parameters and antioxidant status of blood in recreational horses in the winter season. However, the observed results could in part be attributed to the natural physiological adaptation of each individual organism to the treatment.

Developmental and biochemical markers of the impact of pollutant mixtures under the effect of Global Climate Change.

This study investigates the combined impact of microplastics (MP) and Chlorpyriphos (CPF) on sea urchin larvae (Paracentrotus lividus) under the backdrop of ocean warming and acidification. While the individual toxic effects of these pollutants have been previously reported, their combined effects remain poorly understood. Two experiments were conducted using different concentrations of CPF (EC10 and EC50) based on previous studies from our group. MP were adsorbed in CPF to simulate realistic environmental conditions. Additionally, water acidification and warming protocols were implemented to mimic future ocean conditions. Sea urchin embryo toxicity tests were conducted to assess larval development under various treatment combinations of CPF, MP, ocean acidification (OA), and temperature (OW). Morphometric measurements and biochemical analyses were performed to evaluate the effects comprehensively. Results indicate that combined stressors lead to significant morphological alterations, such as increased larval width and reduced stomach volume. Furthermore, biochemical biomarkers like acetylcholinesterase (AChE), glutathione S-transferase (GST), and glutathione reductase (GRx) activities were affected, indicating oxidative stress and impaired detoxification capacity. Interestingly, while temperature increase was expected to enhance larval growth, it instead induced thermal stress, resulting in lower growth rates. This underscores the importance of considering multiple stressors in ecological assessments. Biochemical biomarkers provided early indications of stress responses, complementing traditional growth measurements. The study highlights the necessity of holistic approaches when assessing environmental impacts on marine ecosystems. Understanding interactions between pollutants and environmental stressors is crucial for effective conservation strategies. Future research should delve deeper into the impacts at lower biological levels and explore adaptive mechanisms in marine organisms facing multiple stressors. By doing so, we can better anticipate and mitigate the adverse effects of anthropogenic pollutants on marine biodiversity and ecosystem health.

Dynamics of the content of reactive oxygen species and the state of the glutathione system in the oral cavity during subchronic intoxication wuth the fungicide thiram and its antioxidant correction.

Thiram is a dithiocarbamate derivative, which is used as a fungicide for seed dressing and spraying during the vegetation period of plants, and also as an active vulcanization accelerator in the production of rubber-based rubber products. In this study the content of reactive oxygen species (ROS) and the state of the glutathione system have been investigated in the oral fluid and gum tissues of adult male Wistar rats treated with thiram for 28 days during its administration with food at a dose of 1/50 LD50. Thiram induced formation of ROS in the oral cavity; this was accompanied by an imbalance in the ratio of reduced and oxidized forms of glutathione due to a decrease in glutathione and an increase in its oxidized form as compared to the control. Thiram administration caused an increase in the activity of glutathione-dependent enzymes (glutathione peroxidase, glutathione transferase, and glutathione reductase). However, the time-course of enzyme activation in the gum tissues and oral fluid varied in dependence on the time of exposure to thiram. In the oral fluid of thiram-treated rats changes in the antioxidant glutathione system appeared earlier. The standard diet did not allow the glutathione pool to be fully restored to physiological levels after cessation of thiram intake. The use of exogenous antioxidants resviratrol and an Echinacea purpurea extract led to the restoration of redox homeostasis in the oral cavity.

Antioxidant and Anti-Fatigue Effects of a Standardized Botanical Extract Fraction (HemoHIM) in Forced-Exercised Aged Mice.

HemoHIM is a standardized medicinal herbal preparation consisting of extracts of Angelica gigas Nakai, Cnidium officinale Makino, and Paeonia lactiflora Pallas that possesses immune regulatory activities. This study aimed to research the potential antioxidant effects of HemoHIM and its capacity for reducing fatigue in aged mice subjected to forced exercise. After administering HemoHIM 125 (500 mg/kg orally) for 4 weeks in 8-month-old female C57BL/6 mice (4 groups of 10 mice), various parameters were evaluated. The analyses revealed that HemoHIM enhanced swimming time and grip strength. In addition, it significantly reduced serum lactate levels and increased liver glutathione peroxidase (GPx) levels after exercise challenge. The expression levels of antioxidant enzymes and factors, including nuclear factor erythroid 2-related factor-2 (Nrf-2), heme oxygenase 1, superoxide dismutase, GPx, and glutathione reductase, were significantly higher in liver and muscle tissues of mice treated with HemoHIM. These results indicate that HemoHIM might function as an anti-fatigue and antioxidant agent by modulating the Nrf-2 signaling pathway.

The role of the active site lysine residue on FAD reduction by NADPH in glutathione reductase.

Glutathione reductase (GR) is a two dinucleotide binding domain flavoprotein (tDBDF) that catalyzes the reduction of glutathione disulfide to glutathione coupled to the oxidation of NADPH to NADP+. An interesting feature of GR and other tDBDFs is the presence of a lysine residue (Lys-66 in human GR) at the active site, which interacts with the flavin group, but has an unknown function. To better understand the role of this residue, the dynamics of GR was studied using molecular dynamics simulations, and the reaction mechanism of FAD reduction by NADPH was studied using QM/MM molecular modeling. The two possible protonation states of Lys-66 were considered: neutral and protonated. Molecular dynamics results suggest that the active site is more structured for neutral Lys-66 than for protonated Lys-66. QM/MM modeling results suggest that Lys-66 should be in its neutral state for a thermodynamically favorable reduction of FAD by NADPH. Since the reaction is unfavorable with protonated Lys-66, the reverse reaction (the reduction of NADP+ by FADH-) is expected to take place. A phylogenetic analysis of various tDBDFs was performed, finding that an active site lysine is present in different the tDBDFs enzymes, suggesting that it has a conserved biological role. Overall, these results suggest that the protonation state of the active site lysine determines the energetics of the reaction, controlling its reversibility.

Preparation of spore-immobilized glutathione reductase and its application in inhibiting browning of pear wine.

BACKGROUND: Browning is the key problem hindering the industrialization of pear wine. The use of high-yield glutathione Saccharomyces cerevisiae in the fermentation of pear wine can inhibit browning. Glutathione reductase (GR) can ensure the reduction of glutathione. Spore immobilization of enzymes is a new technology. It is a new attempt to apply spore-immobilized GR in combination with high-yield glutathione S. cerevisiae to inhibit browning of pear wine. RESULTS: Saccharomyces cerevisiae spore immobilization enzyme technology was used to immobilize GR in the spores of mutant S. cerevisiae dit1∆, osw2∆ and chs3∆ and wild-type S. cerevisiae. The enzyme activity of GR immobilized by chs3∆ spores was the highest of 3.08 U mg-1 min-1. The chs3∆ spore-immobilized GR had certain resistance to ethanol, citric acid, sucrose, glucose and proteinase K. Electron microscopy analysis showed that the spore wall of chs3∆ had moderate size holes, which might be the main reason why it immobilized GR with the highest enzyme activity. And the GR was immobilized between the prespore membrane and mannoprotein layer of the spore wall. When chs3∆ spore-immobilized GR (chs3∆-GR) was added to Dangshan pear wine fermented by high-yield glutathione S. cerevisiae JN32-9, the presence of chs3∆-GR could further protect amino acids, polyphenols and glucose from oxidation, thereby reducing the browning of the pear wine during storage by 47.32%. CONCLUSION: GR immobilized by S. cerevisiae spores was effective in inhibiting the browning of pear wine. The method was simple, green and effective and did not increase the production cost of pear wine. © 2024 Society of Chemical Industry.

Silver Organometallics that are Highly Potent Thioredoxin and Glutathione Reductase Inhibitors: Exploring the Correlations of Solution Chemistry with the Strong Antibacterial Effects.

The antibacterial activity of silver species is well-established; however, their mechanism of action has not been adequately explored. Furthermore, issues of low-molecular silver compounds with cytotoxicity, stability, and solubility hamper their progress to drug leads. We have investigated silver N-heterocyclic carbene (NHC) halido complexes [(NHC)AgX, X = Cl, Br, and I] as a promising new type of antibacterial silver organometallics. Spectroscopic studies and conductometry established a higher stability for the complexes with iodide ligands, and nephelometry indicated that the complexes could be administered in solutions with physiological chloride levels. The complexes showed a broad spectrum of strong activity against pathogenic Gram-negative bacteria. However, there was no significant activity against Gram-positive strains. Further studies clarified that tryptone and yeast extract, as components of the culture media, were responsible for this lack of activity. The reduction of biofilm formation and a strong inhibition of both glutathione and thioredoxin reductases with IC50 values in the nanomolar range were confirmed for selected compounds. In addition to their improved physicochemical properties, the compounds with iodide ligands did not display cytotoxic effects, unlike the other silver complexes. In summary, silver NHC complexes with iodide secondary ligands represent a useful scaffold for nontoxic silver organometallics with improved physicochemical properties and a distinct mechanism of action that is based on inhibition of thioredoxin and glutathione reductases.

Purification, structural characterization, and neuroprotective effect of 3,6-diisobutyl-2,5-piperazinedione from Halomonas pacifica CARE-V15 against okadaic acid-induced neurotoxicity in zebrafish model.

Halomonas pacifica CARE-V15 was isolated from the southeastern coast of India to determine its genome sequence. Secondary metabolite gene clusters were identified using an anti-SMASH server. The concentrated crude ethyl acetate extract was evaluated by GC-MS. The bioactive compound from the crude ethyl acetate extract was fractionated by gel column chromatography. HPLC was used to purify the 3,6-diisobutyl-2,5-piperazinedione (DIP), and the structure was determined using FTIR and NMR spectroscopy. Purified DIP was used in an in silico molecular docking analysis. Purified DIP exhibits a stronger affinity for antioxidant genes like glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GSR). Using in silco molecular docking analysis, the protein-ligand binding affinities of GSR (-4.70 kcal/mol), GST (-5.27 kcal/mol), and GPx (-5.37 kcal/mol) were measured. The expression of antioxidant genes were investigated by qRT-PCR. The in vivo reactive oxygen species production, lipid peroxidation, and cell death levels were significantly (p ≤ 0.05) increased in OA-induced group, but all these levels were significantly (p ≤ 0.05) decreased in the purified DIP pretreated group. Purified DIP from halophilic bacteria could thus be a useful treatment for neurological disorders associated with oxidative stress.

Cobalt protoporphyrin modulates antioxidant enzyme activity in the hypothalamus and motor cortex of female rats.

Cobalt protoporphyrin (CoPP) is a synthetic heme analog that has been observed to reduce food intake and promote sustained weight loss. While the precise mechanisms responsible for these effects remain elusive, earlier research has hinted at the potential involvement of nitric oxide synthase in the hypothalamus. This study aimed to delve into CoPP's impact on the activities of crucial antioxidant enzymes: superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST) across seven distinct brain regions (hippocampus, hypothalamus, prefrontal cortex, motor cortex, striatum, midbrain, and cerebellum), as well as in the liver and kidneys. Female Wistar rats weighing 180 to 200 grams received a single subcutaneous dose of 25 µmol/kg CoPP. After six days, brain tissue was extracted to assess the activities of antioxidant enzymes and quantify malondialdehyde levels. Our findings confirm that CoPP administration triggers the characteristic effects of decreased food intake and reduced body weight. Moreover, it led to an increase in SOD activity in the hypothalamus, a pivotal brain region associated with food intake regulation. Notably, CoPP-treated rats exhibited elevated enzymatic activity of catalase, GR, and GST in the motor cortex without concurrent signs of heightened oxidative stress. These results underscore a strong connection between the antioxidant system and food intake regulation. They also emphasize the need for further investigation into the roles of antioxidant enzymes in modulating food intake and the ensuing weight loss, using CoPP as a valuable research tool.

[Clinical and psychopathological characteristics of patients with late-onset schizophrenia and schizophrenia-like psychoses in clusters identified by biological parameters]. / Kliniko-psikhopatologicheskie kharakteristiki bol'nykh s pozdno manifestiruyushchimi shizofreniei i shizofrenopodobnymi psikhozami v klasterakh, vydelennykh po biologicheskim parametram.

OBJECTIVE: To assess clinical and psychopathological characteristics of late-aged female patients with late-onset psychoses in clusters formed on the basis of biochemical and immunological blood parameters. MATERIAL AND METHODS: We examined 59 women with schizophrenia and schizophrenia-like psychoses with onset after 40 years (ICD-10 F20, F22.8, F25, F23, F06.2), including 34 women with late-onset (40-60 years) and 25 with very late onset psychoses (after 60 years). At the time of hospitalization, a clinical/ psychopathological study was carried out using CGI-S, PANSS, CDSS, and HAMD-17, as well as the activities of glutathione reductase (GR) and glutathione-S-transferase (GT) have been determined in erythrocyte hemolysates, and the activities of leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) have been assessed in blood plasma. Biochemical and immunological parameters have been also determined in 34 age-matched mentally healthy women. RESULTS: Clustering by signs such as GR, GT, LE and α1-PI has yielded two clusters of objects (patients) significantly different in GT (p<0.0001), LE (p<0.0001), and α1-PI (p<0.001) activities. Relatively to the controls, in the cluster 1 patients, the activities of GST and α1-PI are increased, the activity of LE is decreased, whereas, in the cluster 2 patients, the activity of GR is decreased, and the activities of LE and α1-PI are increased. Cluster 1 patients differ from cluster 2 patients in greater severity of the condition (CGI-S, p=0.04) and higher total scores on PANSS subscales' items. Cluster 1 includes 76% of patients with very late onset. Different correlations between clinical and biological signs are found in two clusters. CONCLUSION: The identified clusters have different clinical and psychopathological characteristics. Dividing patients into subgroups according to biochemical and immunological parameters is promising for the search for differentiated therapeutic approaches.