Expression Of Glutathione Reductase Research Articles

Integrative transcriptomic and metabolomic analysis to elucidate the effect of gossypol on Enterobacter sp. GD5.

Gossypol, a yellow polyphenolic compound found in the Gossypium genus, is toxic to animals that ingest cotton-derived feed materials. However, ruminants display a notable tolerance to gossypol, attributed to the pivotal role of ruminal microorganisms in its degradation. The mechanisms of how rumen microorganisms degrade and tolerate gossypol remain unclear. Therefore, in this study, Enterobacter sp. GD5 was isolated from rumen fluid, and the effects of gossypol on its metabolism and gene expression were investigated using liquid chromatography-mass spectrometry (LC-MS) and RNA analyses. The LC-MS results revealed that gossypol significantly altered the metabolic profiles of 15 metabolites (eight upregulated and seven downregulated). The Kyoto Encyclopedia of Genes and Genomes analysis results showed that significantly different metabolites were associated with glutathione metabolism in both positive and negative ion modes, where gossypol significantly affected the biosynthesis of amino acids in the negative ion mode. Transcriptomic analysis indicated that gossypol significantly affected 132 genes (104 upregulated and 28 downregulated), with significant changes observed in the expression of catalase peroxidase, glutaredoxin-1, glutathione reductase, thioredoxin 2, thioredoxin reductase, and alkyl hydroperoxide reductase subunit F, which are related to antioxidative stress. Furthermore, Gene Ontology analysis revealed significant changes in homeostatic processes following gossypol supplementation. Overall, these results indicate that gossypol induces oxidative stress, resulting in the increased expression of antioxidative stress-related genes in Enterobacter sp. GD5, which may partially explain its tolerance to gossypol.

Biochar with KMnO4-hematite modification promoted foxtail millet growth by alleviating soil Cd and Zn biotoxicity

The excessive accumulation of Cd and Zn in soil poisons crops and threatens food safety. In this study, KMnO4-hematite modified biochar (MnFeB) was developed and applied to remediate weakly alkaline Cd-Zn contaminated soil, and the heavy metal immobilization effect, plant growth, and metal ion uptake of foxtail millet were studied. MnFeB application reduced the phytotoxicity of soil heavy metals; bioavailable acid-soluble Cd and Zn were reduced by 57.79% and 35.64%, respectively, whereas stable, non-bioavailable, residual Cd and Zn increased by 96.44% and 32.08%, respectively. The chlorophyll and total protein contents and the superoxide dismutase (SOD)activity were enhanced, whereas proline, malondialdehyde, the H2O2 content, glutathione reductase (GR), ascorbate peroxidase (APX) and catalase (CAT) activities were reduced. Accordingly, the expressions of GR, APX, and CAT were downregulated, whereas the expression of MnSOD was upregulated. In addition, MnFeB promoted the net photosynthetic rate and growth of foxtail millet plants. Furthermore, MnFeB reduced the levels of Cd and Zn in the stems, leaves, and grains, decreased the bioconcentration factor of Cd and Zn in shoots, and weakened the translocation of Cd and Zn from roots to shoots. Precipitation, complexation, oxidation-reduction, ion exchange, and π-π stacking interaction were the main Cd and Zn immobilization mechanisms, and MnFeB reduced the soil bacterial community diversity and the relative abundance of Proteobacteria and Planctomycetota. This study provides a feasible and effective remediation material for Cd- and Zn-contaminated soils.

Metabolic and Functional Interactions of H2S and Sucrose in Maize Thermotolerance through Redox Homeodynamics.

Hydrogen sulfide (H2S) is a novel gasotransmitter. Sucrose (SUC) is a source of cellular energy and a signaling molecule. Maize is the third most common food crop worldwide. However, the interaction of H2S and SUC in maize thermotolerance is not widely known. In this study, using maize seedlings as materials, the metabolic and functional interactions of H2S and SUC in maize thermotolerance were investigated. The data show that under heat stress, the survival rate and tissue viability were increased by exogenous SUC, while the malondialdehyde content and electrolyte leakage were reduced by SUC, indicating SUC could increase maize thermotolerance. Also, SUC-promoted thermotolerance was enhanced by H2S, while separately weakened by an inhibitor (propargylglycine) and a scavenger (hypotaurine) of H2S and a SUC-transport inhibitor (N-ethylmaleimide), suggesting the interaction of H2S and SUC in the development of maize thermotolerance. To establish the underlying mechanism of H2S-SUC interaction-promoted thermotolerance, redox parameters in mesocotyls of maize seedlings were measured before and after heat stress. The data indicate that the activity and gene expression of H2S-metabolizing enzymes were up-regulated by SUC, whereas H2S had no significant effect on the activity and gene expression of SUC-metabolizing enzymes. In addition, the activity and gene expression of catalase, glutathione reductase, ascorbate peroxidase, peroxidase, dehydroascorbate reductase, monodehydroascorbate reductase, and superoxide dismutase were reinforced by H2S, SUC, and their combination under non-heat and heat conditions to varying degrees. Similarly, the content of ascorbic acid, flavone, carotenoid, and polyphenol was increased by H2S, SUC, and their combination, whereas the production of superoxide radicals and the hydrogen peroxide level were impaired by these treatments to different extents. These results imply that the metabolic and functional interactions of H2S and sucrose signaling exist in the formation of maize thermotolerance through redox homeodynamics. This finding lays the theoretical basis for developing climate-resistant maize crops and improving food security.

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

BackgroundCurrently, 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. MethodsThe 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. ResultsSerum 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. ConclusionSerum GR can serve as a valuable biomarker for the diagnosis of HCC and for predicting the therapeutic efficacy and prognosis of TACE treatment.

Cytoplasmic Ca2+ influx mediates iron- and reactive oxygen species-dependent ferroptotic cell death in rice immunity.

Iron- and reactive oxygen species (ROS)-dependent ferroptosis occurs in plant cells. Ca2+ acts as a conserved key mediator to control plant immune responses. Here, we report a novel role of cytoplasmic Ca2+ influx regulating ferroptotic cell death in rice immunity using pharmacological approaches. High Ca2+ influx triggered iron-dependent ROS accumulation, lipid peroxidation, and subsequent hypersensitive response (HR) cell death in rice (Oryza sativa). During Magnaporthe oryzae infection, 14 different Ca2+ influx regulators altered Ca2+, ROS and Fe2+ accumulation, glutathione reductase (GR) expression, glutathione (GSH) depletion and lipid peroxidation, leading to ferroptotic cell death in rice. High Ca2+ levels inhibited the reduction of glutathione isulphide (GSSG) to GSH in vitro. Ca2+ chelation by ethylene glycol-bis (2-aminoethylether)-N, N, N', N'-tetra-acetic acid (EGTA) suppressed apoplastic Ca2+ influx in rice leaf sheaths during infection. Blocking apoplastic Ca2+ influx into the cytoplasm by Ca2+ chelation effectively suppressed Ca2+-mediated iron-dependent ROS accumulation and ferroptotic cell death. By contrast, acibenzolar-S-methyl (ASM), a plant defense activator, significantly enhanced Ca2+ influx, as well as ROS and iron accumulation to trigger ferroptotic cell death in rice. The cytoplasmic Ca2+ influx through calcium-permeable cation channels, including the putative resistosomes, could mediate iron- and ROS-dependent ferroptotic cell death under reduced GR expression levels in rice immune responses.

Selenium Lessens Osteoarthritis by Protecting Articular Chondrocytes from Oxidative Damage through Nrf2 and NF-κB Pathways.

Osteoarthritis (OA) causes joint pain and disability due to the abnormal production of inflammatory cytokines and reactive oxygen species (ROS) in chondrocytes, leading to cell death and cartilage matrix destruction. Selenium (Se) intake can protect cells against oxidative damage. It is still unknown whether Se supplementation is beneficial for OA. This study investigated the effects of Se on sodium iodoacetate (MIA)-imitated OA progress in human chondrocyte cell line (SW1353 cells) and rats. The results showed that 0.3 μM of Se treatment could protect SW1353 cells from MIA-induced damage by the Nrf2 pathway by promoting the gene expression of glutathione-synthesis-related enzymes such as the glutamate-cysteine ligase catalytic subunit, the glutamate-cysteine ligase modifier subunit, and glutathione synthetase. In addition, glutathione, superoxide dismutase, glutathione peroxidase, and glutathione reductase expressions are also elevated to eliminate excessive ROS production. Moreover, Se could downregulate NF-κB, leading to a decrease in cytokines, matrix proteases, and glycosaminoglycans. In the rats, MIA-induced cartilage loss was lessened after 2 weeks of Se supplementation by oral gavage; meanwhile, glutathione synthesis was increased, and the expressions of pro-inflammatory cytokines were decreased. These results suggest that Se intake is beneficial for OA due to its effects of decreasing cartilage loss by enhancing antioxidant capacity and reducing inflammation.

Investigation of the effect of isoxazole derivatives on glutathione-dependent enzymes associated with cancer

Globally, cancer is currently the second-most common cause of death. As such, it is a crucial problem that affects society's well-being all around the world. Chemotherapy is the most commonly used treatment for cancer. It is a technique that uses drugs to kill cancerous cells or the cancerous organism itself. Chemotherapy has been used to treat metastatic cancer for the past 50 years, with varying degrees of effectiveness. One of the main problems with many chemotherapeutic drugs is that they might damage healthy cells and organs. These drugs frequently have a low therapeutic index, a restricted ability to selectively target cancerous cells, and a high propensity to develop drug resistance after extended use. Furthermore, a rise in the expression of glutathione reductase (GR; EC 1.8.1.7) and glutathione S-transferase (GST; EC 2.5.1.18) can be seen with time. Extensive study on proteins and their functions in the development of cancer cells has been conducted in recent years. Glutathione-S-transferases (GSTs) are a superfamily of enzymes that play a critical role in the detoxification of cells by protecting them against reactive electrophiles such as chemotherapeutic drugs and reactive oxygen species. Glutathione reductase (GR), on the other hand, is an essential antioxidant enzyme that supports cellular protection against oxidative stress. In addition to its antioxidant role, GR has become a target for the synthesis of antimalarial and anticancer medications. In the current investigation, affinity chromatography was used to purificate the GST and GR enzymes from human erythrocytes. Through the calculation of IC50 and KI values for these derivatives, the effects of isoxazole derivatives on these purified enzymes were examined, with an emphasis on identifying the forms of inhibition.

Glutathione Reductase Expression and Its Prognostic Significance in Colon Cancer.

Maintaining a balanced redox state within cells is crucial for the sustenance of life. The process involves continuous cytosolic disulfide reduction reactions to restore oxidized proteins to their reduced thiol forms. There are two main cellular antioxidant pathways-the thioredoxin (Trx) and glutathione (GSH)/glutaredoxin (Grx) systems. In the GSH/Grx system, glutathione reductase (GR; GSR) catalyses the reduction of GSH disulfide (GSSG) to its sulfhydryl form (GSH), which can then further reduce oxidized Grxs. GR is an essential enzyme that helps in maintaining the supply of reduced glutathione-GSH, which is a significant reducing thiol found in most cells and known for its antioxidant properties. Therefore, it can have a significant impact on cancer development. To investigate this further, we performed an immunohistochemical analysis of GR protein expression in colon adenocarcinoma samples collected from patients with primary colon adenocarcinoma (stage I and II) and patients with metastasis to regional lymph nodes (stage III). The results of our study revealed a significant relationship between the immunohistochemical expression of GR and tumour histological grade, depth of invasion, regional lymph node involvement, staging, and PCNA immunohistochemical expression. It was found that 95% of patients with stage I had low levels of GR expression, whereas 89% of patients with stage III had high levels of immunohistochemical expression. A high level of expression was also detected in the patients with stage II of the disease, where almost 63% were characterized by a high expression of GR. The Western blot method revealed that the highest level of expression was found in the LS 174T cell line, which corresponds to stage II. The results of our study indicate that the immunohistochemical expression of GR may act as an independent prognostic factor associated with colon adenocarcinoma patients' prognosis.

Effects of Deacetylase Inhibition on the Activation of the Antioxidant Response and Aerobic Metabolism in Cellular Models of Fanconi Anemia.

Fanconi anemia (FA) is a rare genetic disease characterized by a dysfunctional DNA repair and an oxidative stress accumulation due to defective mitochondrial energy metabolism, not counteracted by endogenous antioxidant defenses, which appear down-expressed compared to the control. Since the antioxidant response lack could depend on the hypoacetylation of genes coding for detoxifying enzymes, we treated lymphoblasts and fibroblasts mutated for the FANC-A gene with some histone deacetylase inhibitors (HDACi), namely, valproic acid (VPA), beta-hydroxybutyrate (OHB), and EX527 (a Sirt1 inhibitor), under basal conditions and after hydrogen peroxide addition. The results show that VPA increased catalase and glutathione reductase expression and activity, corrected the metabolic defect, lowered lipid peroxidation, restored the mitochondrial fusion and fission balance, and improved mitomycin survival. In contrast, OHB, despite a slight increase in antioxidant enzyme expressions, exacerbated the metabolic defect, increasing oxidative stress production, probably because it also acts as an oxidative phosphorylation metabolite, while EX527 showed no effect. In conclusion, the data suggest that VPA could be a promising drug to modulate the gene expression in FA cells, confirming that the antioxidant response modulation plays a pivotal in FA pathogenesis as it acts on both oxidative stress levels and the mitochondrial metabolism and dynamics quality.

Ferulic acid enhanced resistance against blue mold of Malus domestica by regulating reactive oxygen species and phenylpropanoid metabolism

Postharvest decay of fruit caused by phytopathogen often causes tremendous losses during logistics. Ferulic acid is a kind of phenolic acid which has potential antimicrobial ability and initiates defense responses. This study performed to evaluate the induced resistance of ferulic acid against blue mold of apples (cv. Qiujin) as well as the mechanism involved in its action. Results suggested that 1.0 g L−1 ferulic acid remarkably reduced lesion diameter of Penicillium expansum-inoculated apples and colony diameter in vitro. The activities and gene expressions of catalase, superoxide dismutase, peroxidase, dehydroascorbate reductase, glutathione reductase, monodehydroascorbate reductase, ascorbate peroxidase, and nicotinamide adenine dinucleotide phosphate oxidase were distinctly improved by ferulic acid immersion. Ferulic acid also promoted ascorbic acid and reduced glutathione contents, whereas decreased hydrogen peroxide and malondialdehyde contents in apples. Moreover, ferulic acid enhanced the gene expressions and activities of cinnamyl alcohol dehydrogenase, 4-coumarate coenzyme A ligase, cinnamate-4-hydroxylase, and phenylalanine ammonia-lyase, resulting in caffeic acid, flavonoids, lignin, total phenolics, and p-coumaric acid accumulation in apples. Taken together, ferulic acid could activate the activities and gene expressions of the key enzymes in phenylpropanoid pathway as well as reactive oxygen species metabolism to promote the synthesis of antioxidants and secondary metabolites, thereby increasing disease resistance of apples.

Anti-oxidant effect of nitrite in the pancreatic islets of type 2 diabetic male rats.

Nitrite, a nitric oxide (NO) donor, increases insulin secretion from pancreatic islets and has positive metabolic effects in type 2 diabetes (T2D). Here, we test the hypothesis of whether nitrite-induced insulin secretion is due to blunting of diabetes-induced oxidative stress in the islets. T2D was created in male rats using a combination of streptozotocin at 25 mg/kg and a high-fat diet. Wistar rats were assigned to 3 groups (n=6 in each group), including control, T2D, and T2D+nitrite; the latter group consumed drinking water containing sodium nitrite (50 mg/l) for eight weeks. At the end of the study, mRNA levels of NADPH oxidase (Nox1, 2, 3, and 4), superoxide dismutase (SOD1, 2, and 3), glutathione peroxides (GPX1 and 7), glutathione reductase (GR), catalase, thioredoxin (TXN1 and 2), and thioredoxin reductase (TXNRD1) were measured in the isolated pancreatic islets. In the islets of diabetic rats, mRNA expressions of Nox1, 2, and 4 were higher, whereas expressions of SOD1, 2, catalase, GPX1, 7, GR, and TXN1 were lower than controls. Nitrite significantly (all P-values<0.05) decreased gene expression of Nox1 (0.39-fold) and Nox4 (0.23-fold) and increased gene expression of SOD1 (2.2-fold), SOD2 (2.8-fold), catalase (2.7-fold), GPX1 (2.2-fold), GPX7 (6.0-fold), GR (3.0-fold), TXN1 (2.1-fold), and TXNRD1 (2.3-fold) in diabetic rats. Nitrite decreased oxidative stress in isolated pancreatic islets of rats with T2D by suppressing oxidants and augmenting anti-oxidants. These findings favor the notion that nitrite-induced insulin secretion is partially due to decreased oxidative stress.

MAPK cascade and ROS metabolism are involved in GABA-induced disease resistance in red pitaya fruit

This study investigates the effects of γ-Aminobutyric acid (GABA) and mitogen-activated protein kinase (MAPK) inhibitor (PD98059) in disease resistance in red pitaya fruit. Results demonstrated that GABA treatment suppressed the growth of Gilbertella persicaria; increased H2O2 content and O2•- production rate; enhanced reduced glutathione and ascorbic acid contents, as well as increased the activities and transcripts of catalase (CAT), NADPH oxidase (NOX), peroxidise (POD), superoxide dismutase (SOD), ascorbate peroxidase (APX) and glutathione reductase (GR), and up-regulated HcMYB111/24 expressions. Furthermore, GABA promoted the expressions of HcMAPKKK1-HcMAPKK2/4-HcMAPK1/7 cascades. However, PD98059 +GABA treatment decreased the disease resistance against G. persicaria and reduced H2O2 content; inhibited the activities and gene expressions of NOX, CAT, SOD, POD, GR and APX, and down-regulated the expressions of HcMAPK1/7. These findings suggest that GABA induces disease resistance by regulating ROS metabolism and MAPK cascades in red pitaya fruit.

Overexpression of tomato glutathione reductase (SlGR) in transgenic tobacco enhances salt tolerance involving the S-nitrosylation of GR

S-nitrosylation, a post-translational modification (PTM) dependent on nitric oxide, is essential for plant development and environmental responsiveness. However, the function of S-nitrosylation of glutathione reductase (GR) in tomato (SlGR) under NaCl stress is yet uncertain. In this study, sodium nitroprusside (SNP), an exogenous NO donor, alleviated the growth inhibition of tomato under NaCl treatment, particularly at 100 μM. Following NaCl treatment, the transcripts, enzyme activity, and S-nitrosylated level of GR were increased. In vitro, the SlGR protein was able to be S-nitrosylated by S-nitrosoglutathione (GSNO), significantly increasing the activity of GR. SlGR overexpression transgenic tobacco plants exhibited enhanced germination rate, fresh weight, and increased root length in comparison to wild-type (WT) seedlings. The accumulation of reactive oxygen species (ROS) was lower, whereas the expression and activities of GR, ascorbate peroxidase (APX), superoxide dismutase (SOD), and catalase (CAT); the ratio of ascorbic acid/dehydroascorbic acid (AsA/DHA), reduced glutathione/oxidized glutathione (GSH/GSSG), total soluble sugar and proline contents; and the expression of stress-related genes were higher in SlGR overexpression transgenic plants in comparison to the WT plants following NaCl treatment. The accumulation of NO and S-nitrosylated levels of GR in transgenic plants was higher in comparison to WT plants following NaCl treatment. These results indicated that S-nitrosylation of GR played a significant role in salt tolerance by regulating the oxidative state.

Chemical Characterization, Antioxidant Capacity and Anti-Oxidative Stress Potential of South American Fabaceae Desmodium tortuosum.

It has been proposed that oxidative stress is a pathogenic mechanism to induce cytotoxicity and to cause cardiovascular and neuronal diseases. At present, natural compounds such as plant extracts have been used to reduce the cytotoxic effects produced by agents that induce oxidative stress. Our study aimed to evaluate the antioxidant and cytoprotective capacity of Desmodium tortuosum (D. tortuosum) extract in the co- and pre-treatment in EA.hy926 and SH-SY5Y cell lines subjected to oxidative stress induced by tert-butylhydroperoxide (t-BOOH). Cell viability, reactive oxygen species (ROS), nitric oxide (NO), caspase 3/7 activity, reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), and molecular expression of oxidative stress biomarkers (SOD2, NRF2 and NFκB1) and cell death (APAF1, BAX, Caspase3) were all evaluated. It was observed that the D. tortuosum extract, in a dose-dependent manner, was able to reduce the oxidative and cytotoxicity effects induced by t-BOOH, even normalized to a dose of 200 µg/mL, which would be due to the high content of phenolic compounds mainly phenolic acids, flavonoids, carotenoids and other antioxidant compounds. Finally, these results are indicators that the extract of D. tortuosum could be a natural alternative against the cytotoxic exposure to stressful and cytotoxic chemical agents.

Effects of in ovo feeding of chlorogenic acid on antioxidant capacity of postnatal broilers.

In this study, chlorogenic acid (CGA) was injected into the amniotic cavity of chicken embryos to study the effects of in ovo feeding of CGA on the antioxidant capacity of postnatal broilers. On the 17th day of embryonic age, a total of 300 healthy broiler fertile eggs with similar weights were randomly subjected to five groups as follows; in ovo injection with 0.5ml CGA at 4 mg/egg (4CGA) or 7 mg/egg (7CGA) or 10 mg/egg (10CGA), or sham-injection with saline (positive control, PC) or no injection (negative control, NC). Each group had six replicates of ten embryos. Six healthy chicks with similar body weights hatched from each replicate were selected and reared until heat stress treatment (35°C ± 1°C, 8h/d) at 28-42days of age. The results showed that there was no significant difference in the hatching rate between the groups (p > 0.05). After heat stress treatment, 4CGA group showed an improved intestinal morphology which was demonstrated by a higher villus height in the duodenum and a higher villus height/crypt depth ratio in the jejunum, compared with the NC group (p < 0.05). The antioxidant capacity of chickens was improved by in ovo feeding of CGA since 4CGA decreased the plasma content of malondialdehyde (MDA) (p < 0.05), whereas, it increased the superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) activities compared with NC group (p < 0.05). Also, the MDA content of the different injection groups had a quadratic effect, with the 4CGA group having the lowest MDA content (P quadratic < 0.05). In the duodenum, 4CGA injection significantly increased the mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (H O -1), glutathione synthetase (GSS), and SOD1 compared to the NC and PC groups (p < 0.05). The mRNA expressions of glutathione reductase (GSR) and GPX7 were significantly increased in all CGA-treated groups compared with the PC group (p < 0.05), while the mRNA expression of CAT was significantly increased by 4CGA group than the NC group (p < 0.05). The mRNA expressions of epigenetic-related genes, ten eleven translocation 1 and 2 (Tet1 and Tet2), and DNA-methyltransferase 3 alpha (DNMT3A) in the duodenum of 4CGA injected group was significantly increased compared with the NC and PC groups (p < 0.05). The mRNA expressions of Nrf2, SOD1, and Tet2 showed a significant quadratic effects with the 4CGA group having the highest expression (P quadratic < 0.05). In conclusion, in ovo feeding of CGA alleviated heat stress-induced intestinal oxidative damage. Injection with CGA of 4 mg/egg is considered most effective due to its actions in improving intestinal antioxidant capacity, especially in the duodenum. The antioxidant effects of in ovo CGA on postnatal heat-stressed broilers may be related to its regulation of epigenetic mechanisms. Thus, this study provides technical knowledge to support the in ovo feeding of CGA to alleviate oxidative stress in postnatal heat-stressed broilers.

SLC27A5 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by downregulating glutathione reductase

Sorafenib, a first-line drug for advanced hepatocellular carcinoma (HCC), shows a favorable anti-tumor effect while resistance is a barrier impeding patients from benefiting from it. Thus, more efforts are needed to lift this restriction. Herein, we first find that solute carrier family 27 member 5 (SLC27A5/FATP5), an enzyme involved in the metabolism of fatty acid and bile acid, is downregulated in sorafenib-resistant HCC. SLC27A5 deficiency facilitates the resistance towards sorafenib in HCC cells, which is mediated by suppressing ferroptosis. Further mechanism studies reveal that the loss of SLC27A5 enhances the glutathione reductase (GSR) expression in a nuclear factor erythroid 2-related factor 2 (NRF2)-dependent manner, which maintains glutathione (GSH) homeostasis and renders insensitive to sorafenib-induced ferroptosis. Notably, SLC27A5 negatively correlates with GSR, and genetic or pharmacological inhibition of GSR strengthens the efficacy of sorafenib through GSH depletion and the accumulation of lipid peroxide products in SLC27A5-knockout and sorafenib-resistant HCC cells. Based on our results, the combination of sorafenib and carmustine (BCNU), a selective inhibitor of GSR, remarkably hamper tumor growth by enhancing ferroptotic cell death in vivo. In conclusion, we describe that SLC27A5 serves as a suppressor in sorafenib resistance and promotes sorafenib-triggered ferroptosis via restraining the NRF2/GSR pathway in HCC, providing a potential therapeutic strategy for overcoming sorafenib resistance.

Functional expression, localization, and biochemical characterization of thioredoxin glutathione reductase from air-breathing magur catfish, Clarias magur

The glutathione (GSH) and thioredoxin (Trx) systems regulate cellular redox homeostasis and maintain antioxidant defense in most eukaryotes. We earlier reported the absence of gene coding for the glutathione reductase (GR) enzyme of the GSH system in the facultative air-breathing catfish, Clarias magur. Here, we identified three thioredoxin reductase (TrxR) genes, one of which was later confirmed as a thioredoxin glutathione reductase (TGR). We then characterized the novel recombinant TGR enzyme of C. magur (CmTGR). The tissue-specific expression of the txnrd genes and the tissue-specific activity of the TrxR enzyme were analyzed. The recombinant CmTGR is a dimer of ~133 kDa. The protein showed TrxR activity with 5,5′-diothiobis (2-nitrobenzoic acid) reduction assay with a Km of 304.40 μM and GR activity with a Km of 58.91 μM. Phylogenetic analysis showed that the CmTGR was related to the TrxRs of fishes and distantly related to the TGRs of platyhelminth parasites. The structural analysis revealed the conserved glutaredoxin active site and FAD- and NADPH-binding sites. To our knowledge, this is the first report of the presence of a TGR in any fish. This unusual presence of TGR in C. magur is crucial as it helps maintain redox homeostasis under environmental stressors-induced oxidative stress.

Effects of blueberry anthocyanins on perfluorooctane sulfonate-induced oxidative stress and mitochondrial dysfunction in dugesia japonica

The effects of blueberry anthocyanins against perfluorooctane sulfonate on antioxidant-related gene expression levels, antioxidase activities, malondialdehyde content, glutathione/oxidized glutathione ratios, mitochondrial metabolic enzyme activities, and mitochondrial permeability transition pore opening rates were examined in the planarian Dugesia japonica. Glutathione reductase, glutathione peroxidase, and glutathione S-transferase gene expression levels were up-regulated on day 1 and then down-regulated following exposure to 5 mg/L perfluorooctane sulfonate with those of the control. The activities of the three corresponding enzymes were inhibited by perfluorooctane sulfonate and activated by anthocyanins. Malondialdehyde contents and mitochondrial permeability transition pore opening rates as well as the activities of mitochondrial metabolic enzymes, also increased and the glutathione/oxidized glutathione ratio decreased. Anthocyanin treatments have an alleviating effect on the disorder caused by perfluorooctane sulfonate.

Dimethylthiourea Alleviates Drought Stress by Suppressing Hydrogen Peroxide-Dependent Abscisic Acid-Mediated Oxidative Responses in an Antagonistic Interaction with Salicylic Acid in Brassica napus Leaves.

In plants, prolonged drought induces oxidative stress, leading to a loss of reducing potential in redox components. Abscisic acid (ABA) is a representative hormonal signal regulating stress responses. This study aimed to investigate the physiological significance of dimethylthiourea (DMTU, an H2O2 scavenger) in the hormonal regulation of the antioxidant system and redox control in rapeseed (Brassica napus L.) leaves under drought stress. Drought treatment for 10 days provoked oxidative stress, as evidenced by the increase in O2•- and H2O2 concentrations, and lipid peroxidation levels, and a decrease in leaf water potential. Drought-induced oxidative responses were significantly alleviated by DMTU treatment. The accumulation of O2•- and H2O2 in drought-treated plants coincided with the enhanced expression of the NADPH oxidase and Cu/Zn-SOD genes, leading to an up-regulation in oxidative signal-inducible 1 (OXI1) and mitogen-activated protein kinase 6 (MAPK6), with a concomitant increase in ABA levels and the up-regulation of ABA-related genes. DMTU treatment under drought largely suppressed the drought-responsive up-regulation of these genes by depressing ABA responses through an antagonistic interaction with salicylic acid (SA). DMTU treatment also alleviated the drought-induced loss of reducing potential in GSH- and NADPH-based redox by the enhanced expression of glutathione reductase 1 (GR1) and up-regulation of oxidoreductase genes (TRXh5 and GRXC9). These results indicate that DMTU effectively alleviates drought-induced oxidative responses by suppressing ABA-mediated oxidative burst signaling in an antagonistic regulation of SA.

Hydrogen sulfide treatment improves quality attributes via regulating the antioxidant system in goji berry (Lycium barbarum L.)

Hydrogen sulfide (H2S) has been identified as a critical gaseous signaling chemical. Herein, the effects of H2S treatment on the postharvest goji berries and antioxidant enzyme activities were determined. H2S application delayed the decay index, loss of firmness, color, flavor, and total sugars and loss of total protein, betaine and ascorbic acid in goji berries during postharvest storage. Meanwhile, H2S noticeably reduced the MDA, H2O2, and O2− accumulation. Additionally, it was shown that H2S increased the activity of catalase (CAT), ascorbate peroxidase (APX), peroxidase (POD), glutathione reductase (GR) and superoxide dismutase (SOD) while decreased the quantity of lipoxygenase (LOX). The mRNA expression of LDC, DCD, CAT, APX, POD, GR and SOD was up-regulated but LOX, RBOH-b and RBOH-e was down-regulated in goji berries after H2S treatment. Altogether, H2S could efficiently delay the senescence, improves postharvest quality, increase the bioactive compounds accumulation, and boost the antioxidant capacity of goji berries through modulating antioxidant enzyme system.