Search Results (244)

Oxidative stress (OS) occurs when there is an imbalance between oxidants and antioxidants, leading to disruptions in cellular signaling and causing damage to molecules. Glutathione S-transferase (GST) enzymes are crucial for maintaining redox balance by facilitating glutathione conjugation. Increased oxidative damage has been noted during the COVID-19 pandemic, and its persistence may be linked to the onset of long COVID. This systematic review aimed to assess the relationship between GST gene polymorphisms and the prognosis of COVID-19, including long COVID. Adhering to the PRISMA guidelines, a thorough search was carried out in MEDLINE, CENTRAL, PubMed, and EMBASE for studies published from September 2020 to February 2025. Out of an initial selection of 462 articles, ten studies (four concerning COVID-19 severity and six related to long COVID) satisfied the inclusion criteria. The findings regarding GST polymorphisms were not consistent, especially concerning the GSTM1 and GSTT1 isoforms. Nevertheless, evidence indicates a sustained state of oxidative stress in patients with long COVID. The majority of research has focused on cytosolic GSTs, while the functions of microsomal and mitochondrial GST families remain largely unexplored. These findings suggest that further research into the various GST subfamilies and their genetic variants is necessary to enhance our understanding of their impact on COVID-19 severity and the pathophysiology of long COVID. Full article

Farmers commonly throw away tomato leaves when they harvest tomatoes, although they are a good source of vital biomolecules. ZnO nanoparticles (ZnO NPs) enhance plant growth by regulating abiotic stress and scavenging reactive oxygen species. In the current article, the activities of five antioxidant enzymes—glutathione reductase (GR), peroxidase (POX), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT)—were determined spectrophotometrically to study the interaction between foliar fertilization of ZnO NPs and salt stress in tomato plants. We employed the next-generation sequencing (NGS) technique to investigate the gene expression. It was also used to generate a de novo supertranscript and then determine the sequences modulated by treatments. Differential expression analysis was used to identify increased and reduced gene clusters, and gene enrichment analysis was used to identify over- and under-expressed genes under the treatment. Gene Ontology (GO) was used to identify the functions and regulatory pathways of the differentially expressed genes (DEGs). It was found that ZnO nanoparticles had the capability to overcome the reduction in antioxidant enzyme production levels in the case of the salinity-stressed treatments and enhance the secretion of those enzymes in the non-stressed but sprayed treatments. The ZnO NPs also enhanced the reduction in stress-responsive genes associated with salt stress resistance. The results revealed the impact of ZnO nanoparticles on alleviating the salinity stress reductive effects in antioxidative enzymes and regulating the mechanism by which metabolically relevant genes adaptively respond to salt stress in tomato plants. So, spraying tomato plants (stressed or not) with ZnO NPs is a promising agricultural technique in improving different metabolic pathways that are responsible for plants’ resistance. Full article

This study evaluated the inhibitory activity of quercetin at sub-inhibitory concentrations on quorum-sensing (QS) molecules in vitro and the effects of dietary supplementation with quercetin (for 24 consecutive days) on enterotoxigenic Escherichia coli (ETEC)-induced inflammatory and oxidative stress responses in weaned piglets. The piglets were fed one of three diets: the basal diet (Con), ETEC challenge (K88) after the basal diet, or ETEC challenge (quercetin + K88) after the basal diet supplemented with 0.2% quercetin. In vitro experiments revealed that 5 mg/mL quercetin exhibited the strongest QS inhibitory activity and reduced pigment production by Chromobacterium violaceum ATCC12472 by 67.70%. In vivo experiments revealed that quercetin + K88 significantly increased immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) levels in the serum, ileum mucosa, and colon mucosa; increased glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) levels in the serum, liver, and colon mucosa; and decreased cluster of differentiation 3 (CD3) and cluster of differentiation 8 (CD8)activity in the serum compared with K88 alone. Quercetin + K88 significantly alleviated pathological damage to the liver and spleen and upregulated antioxidant genes (nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1(HO-1), CAT, SOD, and glutathione s-transferase (GST)). Inducible nitric oxide synthase (iNOS) and kelch-like ech-associated protein 1 (Keap1), which cause oxidative damage to the liver and spleen, were significantly downregulated. The acetic acid content in the cecum was significantly increased, and the E. coli count and QS signal molecule autoinducer-2 (AI-2) yield were significantly reduced. In conclusion, 0.2% dietary quercetin can alleviate ETEC-induced inflammation and oxidative stress in weaned piglets. Full article

Background: Butylated hydroxyanisole (BHA) has been extensively used in several commercial industries as a preservative. It causes severe cellular and neurological damage affecting the developing fetus and might induce attention deficit hyperactivity disorder (ADHD). Methods: Zebrafish embryos were subjected to five distinct doses of BHA—0.5, 1, 2, 4, and 8 ppb up to 96 h post fertilization (hpf). Hatching rate, heart rate, and body malformations were assessed at 48 hpf, 72 hpf, and 48–96 hpf, respectively. After exposure, apoptotic activity, neurobehavioral evaluation, neurotransmitter assay, and antioxidant activity were assessed at 96 hpf. At 120 hpf, the expression of genes DRD4, COMT, 5-HTR1aa, and BDNF was evaluated by real-time PCR. Results: BHA exposure showed a delay in the hatching rate and a decrease in the heart rate of the embryo when compared with the control. Larvae exhibited developmental deformities such as bent spine, yolk sac, and pericardial edema. A higher density of apoptotic cells was observed in BHA-exposed larvae at 96 hpf. There was a decline in catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and superoxide dismutase (SOD) activity, indicating oxidative stress. There was a significant decrease in Acetylcholinesterase (AChE) activity and serotonin levels with an increase in concentration of BHA, leading to a dose-responsive increase in anxiety and impairment in memory. A significant decrease in gene expression was also observed for DRD4, COMT, 5-HTR1aa, and BDNF. Conclusions: Even at lower concentrations of BHA, zebrafish embryos suffered from developmental toxicity, anxiety, and impaired memory due to a decrease in AChE activity and serotonin levels and altered the expression of the mentioned genes. Full article

Bombyx mori, a key lepidopteran model with economic importance, is highly susceptible to environmental heavy metal pollution. This study investigated the mechanisms of Pb toxicity and the associated detoxification and metabolic defense responses in silkworms, employing transcriptome sequencing, enzyme activity assays, and histopathological analysis. Pb exposure caused significant histopathological changes and apoptosis in the fat body, marked by structural disorganization, swollen adipocytes, and degraded extracellular matrix. Molecular analysis showed activation of antioxidant defenses, with superoxide dismutase (SOD) and catalase (CAT) activities significantly elevated (p < 0.05), while peroxidase (POD) activity declined (p < 0.05). Levels of malondialdehyde (MDA) and glutathione (GSH) also decreased. In detoxification responses, carboxylesterase (CarE) activity was reduced, whereas cytochrome P450 (P450) and glutathione S-transferase (GST) activities increased (p < 0.05). Transcriptome sequencing revealed 1,418 differentially expressed genes (DEGs), with notable upregulation of key detoxification genes (p < 0.05), including six cytochrome P450s (CYPs), five uridine diphosphate-glycosyltransferases (UGTs), three glutathione S-transferases (GSTs), and six ATP-binding cassette transporters (ABCs). KEGG enrichment analysis highlighted the involvement of these DEGs in drug metabolism, glutathione metabolism, and ABC transporter pathways (p < 0.05). Functional validation showed that knocking down Cap ‘n’ Collar C (CncC) significantly suppressed key detoxification genes (CYP18A1, CYP332A1, GSTd3, GSTt1, UGT33D8; p < 0.05). qRT-PCR and Western blot analyses confirmed that the Caspase-3 pathway mediates Pb-induced apoptosis, with increased cleaved Caspase-3 and Caspase-4 levels following CncC silencing. Overall, our findings elucidate the mechanisms of Pb toxicity in silkworms and identify CncC as a critical regulator of detoxification and defense against heavy metal stress in lepidopteran insects. Full article

Citral, an organic compound found in lemongrass (Cymbopogon citratus) oil and Litsea cubeba essential oil, has been reported to exhibit notable antifungal activity against Magnaporthe oryzae (M. oryzae), the pathogen of rice blast, which causes significant economic losses in rice production. However, the role of citral in inducing oxidative stress related to antifungal ability and its underlying regulatory networks in M. oryzae remain unclear. In this study, we investigated the oxidative effects of citral on M. oryzae and conducted transcriptomic and widely targeted metabolomic (WTM) analyses on the mycelia. The results showed that citral induced superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) activities but reduced glutathione S-transferase (GST) activity with 25% maximal effective concentration (EC₂₅) and 75% maximal effective concentration (EC₇₅). Importantly, citral at EC₇₅ reduced the activities of mitochondrial respiratory chain complex I, complex III and ATP content, while increasing the activity of mitochondrial respiratory chain complex II. In addition, citral triggered a burst of reactive oxygen species (ROS) and a loss of mitochondrial membrane potential (MMP) through the observation of fluorescence. Furthermore, RNA-seq analysis and metabolomics analysis identified a total of 466 differentially expression genes (DEGs) and 32 differential metabolites (DAMs) after the mycelia were treated with citral. The following multi-omics analysis revealed that the metabolic pathways centered on AsA, GSH and melatonin were obviously suppressed by citral, indicating a disrupted redox equilibrium in the cell. These findings provide further evidences supporting the antifungal activity of citral and offer new insights into the response of M. oryzae under oxidative stress induced by citral. Full article

The widespread use and pseudo-persistent occurrence of the antidepressant citalopram (CIT) could pose a potential ecological risk in the aquatic environment. The message about the bioconcentration and sensitive biomarker identification of CIT at the environmentally relevant concentrations is limited. In this study, an integral evaluation of the phenotypic and biochemical effects of CIT on Daphnia magna (D. magna) was conducted at 0.5 and 10 µg/L. The biomarker screening includes energy metabolism, phototactic behavior, feeding dysfunction, and antioxidant stress responses. The carbohydrate, lipid, and protein content was determined using the assay of anthrone with glucose as standard, thiophosphorate-Vaniline with cholesterol as standard, and Coomassie brilliant blue with serum albumin as standard, respectively. The results showed the bioconcentration equilibrium of CIT reached at the exposure duration of 48 h during the uptake process. At the exposure concentrations of 0.5 and 10 µg/L, the bioconcentration factor of CIT was 571.2 and 67.4 L/kg, respectively. Both protein and lipid content significantly increased at 0.5 µg/L with a 1.78-fold elevation in total energy. Comparatively, the lipid content showed a significant increase at 10 µg/L, while the available total energy rose by 1.25-fold relative to the control group. The phototactic behavior of D. magna exposed to 0.5 µg/L CIT was markedly reduced at 48 h relative to control. In contrast, a significant decrease in phototaxis was observed after 6 h and then a significant increase at 12 h with a continuously obvious decline at 10 µg/L. The filtration rates were increased by 32% compared to controls at 0.5 µg/L, while the stimulatory effects disappeared at 10 µg/L. With regarding to the antioxidant enzyme activities, CIT exposure significantly inhibited the catalase activity both at 0.5 and 10 µg/L, while the glutathione S-transferase activity was obviously induced at 0.5 µg/L and inhibited at 10 µg/L. The expression level of 18s gene was significantly decreased at 10 µg/L. Only the gst gene expression level was significantly increased at 0.5 µg/L, while the 18s and cat gene expression level was obviously inhibited and induced at 10 µg/L. Comprehensively, the responses of the phenotypic traits and energy metabolism of D. magna at various environmental concentrations were sensitive for CIT. This study provided basic data for the risk estimation of CIT in the real freshwater environment. Full article

The life expectancy of patients with psychotic disorders is significantly shorter than that of the general population; antipsychotic-induced metabolic disorders play a significant role in reducing life expectancy. Both metabolic syndrome (MetS) and schizophrenia are multifactorial conditions. One area where the two conditions overlap is oxidative stress, which is present in both diseases. The glutathione-S-transferase (GST) system is a major line of defense against exogenous toxicants and oxidative damage to cells. The aim of our study was to perform an association analysis of gene polymorphisms with metabolic disorders in patients with schizophrenia treated with antipsychotic therapy. Methods: A total of 639 white patients with schizophrenia (ICD-10) from Siberia (Russia) were included in the study. Genotyping was carried out using real-time polymerase chain reaction for two single-nucleotide polymorphisms (SNPs) in the GSTP1 (rs614080 and rs1695) and one SNP in the GSTO1 (rs49252). Results: We found that rs1695*GG genotype of GSTP1 is a risk factor for the development of overweight (OR 2.36; 95% CI: 1.3–4.29; p = 0.0054). In the subgroup of patients receiving first-generation antipsychotics as basic therapy, the risk of overweight was associated with carriage of the rs1695*GG (OR 5.43; 95% CI: 2.24–13.16; p < 0.001) genotype of GSTP1 in a recessive model of inheritance. In contrast, an association of rs1695*G GSTP1 with obesity (OR: 0.42; 95% CI: 0.20–0.87; p = 0.018) was shown in the dominant model of inheritance in patients receiving second-generation antipsychotics. Conclusions: The pilot results obtained confirm the hypothesis of a violation of the antioxidant status, in particular the involvement of GSTP1, in the development of antipsychotic-induced metabolic disorders in schizophrenia. Further studies with larger samples and different ethnic groups are needed to confirm the obtained results. Full article

Chlorfenapyr is a widely used insecticide known to harm non-target insects, but its effects on reproductive development in the silkworm (Bombyx mori L.) remain incompletely understood. In this study, we investigated the histopathological and transcriptional changes in the gonads (ovaries and testes) of newly molted fifth-instar silkworm larvae exposed to chlorfenapyr. Histopathological analysis revealed delayed gonadal development, a reduction in oogonia and oocytes in the ovaries, and decreased numbers of spermatocytes in the testes. Transcriptome analysis identified significant differentially expressed genes (DEGs), mainly enriched in pathways such as “Drug metabolism—cytochrome P450”, “Insect hormone biosynthesis”, and “Ribosome”. Key up-regulated genes included members of the cytochrome P450 family (CYP6B5, CYP9f2, CYP6B6), glutathione S-transferases (GSTT1, GST1), and juvenile hormone-related enzymes (JHAMT, JHEH), indicating active detoxification and hormonal regulation responses. Several transcription factor families, particularly C2H2, HB-other, and TRAF, exhibited altered expression, suggesting roles in stress adaptation. Protein–protein interaction (PPI) network analysis identified hub genes such as EcR, Kr-h1, and various ribosomal proteins, highlighting their potential involvement in reproductive development. Quantitative PCR (qPCR) validated the transcriptomic data, confirming the reliability of the results. Overall, these findings enhance our understanding of chlorfenapyr’s impact on silkworm reproductive development and the underlying molecular mechanisms, providing valuable insights for sustainable pest management and ecological risk assessment of insecticides. Full article

(1) Background: This study evaluated the potential of a synthetic peptide (SGHPGAMGPVGPR), identified in the bullfrog (Lithobates catesbeianus) skin, in regulating inflammation and oxidative stress using RAW 264.7 macrophages; (2) Methods: Molecular docking determined its optimal interaction with cyclooxygenase (COX-2) an enzyme related to the production of prostaglandins, which play a crucial essential role in the inflammatory response. The peptide was commercially synthesized company, and its antioxidant capacity was assessed using DPPH and FRAP assays. Cell viability, nitric oxide (NO) levels, catalase (CAT), superoxide dismutase (SOD) and glutathione s-transferase (GST) activity, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) gene expression and cell production were additionally quantified. (3) Results: The peptide SGHPGAMGPVGPR, designated as P1, exhibited remarkable free radical scavenging capacity, antioxidant, and anti-inflammatory activities. No significant difference was observed in SOD and CAT activity in P1-treated macrophages, likely due to downregulation in the Nrf2/HO-1 pathway. Reduced GST activity was observed in these cells, which was potentially associated with TNF-α downregulation; (4) Conclusions: These findings suggest that P1 modulates the antioxidant response through pathways independent of classical antioxidant enzymes. Furthermore, decreased IL-6, COX2, and nuclear factor kappa B (NF-κB) expression was observed, indicating the involvement of a key pathway in the regulation of the OxInflammation process. Full article

Fungal diseases of agricultural crops cause severe economic losses to the growers. For the control of these diseases, azoxystrobin is one of the recommended fungicides. This fungicide is systemic in action and is expected to reach the floral part of the treated crop and its residue in the pollen and nectar, the natural food sources of honey bees, which could be collected and fed on by honey bees, thus affecting their health. The purpose of this study was to determine the physiological and chemical changes caused by this fungicide in honey bee workers (Apis mellifera L). Workers of this honey bee at 1, 8, and 21 days old were treated with 125, 167, and 250 mg/L concentrations of azoxystrobin for seven days; their survival rates, activities of carboxylesterase (CarE), glutathione S-transferases (GSTs), cytochrome P450 enzyme (CYP450), catalase (CAT), and superoxide dismutase (SOD) enzymes, and the expression levels of immune (Aba, Api, Def1, and Hym) and nutrition genes (Ilp1, Ilp2, and Vg) were detected. Our findings revealed that azoxystrobin affected the survival of workers, particularly 1- and 21-day-old workers, who responded to azoxystrobin stress with increased activities of detoxification and protective enzymes, which might have physiological costs. Additionally, azoxystrobin affected the expression of immune and nutrition genes, with a decreased expression trend in 21-day-old workers compared to the 1- and 8-day-old workers, leading to reduced resistance to external stressors and increased mortality rates. These findings provide important insights into the adverse effects of azoxystrobin on workers of different ages and emphasize the potential risks of this chemical to colony stability and individual health. This study recommends an urgent ban on such a harmful fungicide being used for fungi control in agriculture, especially during plant flowering. Full article

Alzheimer’s disease (AD) is characterized by oxidative stress, amyloid-beta (Aβ) deposition, and tau hyperphosphorylation. While polysaccharides have demonstrated anti-AD effects, the properties of Cremastra appendiculata polysaccharides (CAPs) remain underexplored. This study evaluates the physicochemical properties, antioxidant activity, anti-AD effects, and underlying mechanisms of CAP in vitro and in Caenorhabditis elegans (C. elegans) AD models. CAP, containing 22.37% uronic acid, is stable below 270 °C and adopts a triple helix structure. Scanning electron microscopy (SEM) reveals an irregular layered architecture. In vitro, CAP exhibits significant antioxidant activity, protecting PC12 cells from Aβ-induced cytotoxicity. In C. elegans, CAP extends the lifespan in a concentration-dependent manner without affecting growth, alleviating tau-induced locomotor defects, reducing Aβ-induced paralysis and serotonin hypersensitivity, and decreasing Aβ deposition by 79.96% at 2.0 mg/mL. CAP enhances antioxidant capacity and heat resistance by reducing reactive oxygen species (ROS) levels and increasing glutathione S-transferase 4 (GST-4) and glutathione peroxidase (GSH-Px) activities. Additionally, CAP upregulates key genes in the insulin/insulin-like growth factor signaling pathway, including daf-16 and skn-1, along with their downstream targets (sod-3, ctl-1, gst-4, hsp-70). These findings suggest that CAP has potent antioxidant and anti-AD effects, alleviating Aβ- and tau-induced toxicity, and may serve as a promising therapeutic agent for Alzheimer’s disease. Full article

Polycyclic aromatic hydrocarbons (PAHs) and global warming impact aquatic ecosystems, eventually interacting. Monolayer (2D) cultures of cell lines, such as the rainbow trout liver RTL-W1, are employed for unveiling toxicological effects in fish. Nonetheless, three-dimensional (3D) models constitute an alternate paradigm, better emulating in vivo responses. Here, ultra-low attachment (ULA) plates were used to generate ten-day-old RTL-W1 spheroids for exposure to a control, a solvent control (0.1% DMSO) and the model PAH benzo[k]fluoranthene (BkF) at 10 and 100 nM and at 18 and 23 °C (thermal stress). After a 4-day exposure, spheroids were analyzed for viability (alamarBlue and lactate dehydrogenase), biometry (area, diameter and sphericity), histocytology (optical and electron microscopy), and mRNA levels of the detoxification-related genes cytochrome P450 (CYP)1A, CYP3A27, aryl hydrocarbon receptor (AhR), glutathione S-transferase (GST), uridine diphosphate–glucuronosyltransferase (UGT), catalase (CAT), multidrug resistance-associated protein 2 (MRP2) and bile salt export protein (BSEP). Immunocytochemistry (ICC) was used to assess CYP1A protein expression. Neither temperature nor BkF exposure altered the spheroids’ viability or biometry. BkF modified the cell’s ultrastructure. The expression of CYP1A was augmented with both BkF concentrations, while AhR’s increased at the higher concentration. The CYP1A protein showed a dose-dependent increase. Temperature and BkF concurrently modelled UGT’s expression, which increased in the 100 nM condition at 23 °C. Conversely, CYP3A27, MRP2, and BSEP expressions lowered at 23 °C. CAT and GST mRNA levels were uninfluenced by either stressor. Overall, BkF and temperature impacted independently or interactively in RTL-W1 spheroids. These seem to be useful novel tools for studying the liver-related effects of temperature and PAHs. Full article

Selenium (Se) is an essential trace element for humans, and the production of Se-enriched rice (Oryza sativa) is a key approach for Se supplementation. Nevertheless, the effects of different Se forms and concentrations on the metabolism and aboveground absorption pathways of rice seedlings are not yet well-understood. Therefore, we conducted a hydroponic experiment and used transcriptome analysis to study the absorption and transformation processes of sodium selenite (Na₂SeO₃) and selenomethionine (SeMet) in rice at the seedling stage. The aboveground (stem + leaf) Se concentration at the seedling stage was higher under the SeMet treatments, and low Se applications (<25 μM) significantly promoted rice growth. Selenocysteine (SeCys) and SeMet were the primary forms of Se in rice, accounting for 57–86.35% and 7.6–31.5%, respectively, while selenate [Se (VI)] significantly increased when Se levels exceeded 25 μM. In the transcriptome, differentially expressed genes (DEGs) were significantly enriched in the following pathways: carbon metabolism, amino acid biosynthesis, and glutathione metabolism. In the Na₂SeO₃ treatments, genes encoding phosphoglycerate mutase (PGM), triosephosphate isomerase (TPI), phosphofructokinase (PFK), pyruvate kinase (PK), malate dehydrogenase (MDH), polyamine oxidase (PAO), aspartate aminotransferase (AST), and glutathione S-transferase (GST) were upregulated, and the expression levels of differentially expressed genes (DEGs) decreased with increasing Se levels. SeMet treatments upregulated genes encoding PFK, PK, glutamine synthetase (NADH-GOGAT), and L-ascorbate peroxidase (APX), and expression levels of DEGs increased with increasing Se levels. This study provides important insights into the molecular mechanisms of the uptake and metabolism of different Se forms in rice at the seedling stage. Full article

The rose (Rosa chinensis), with its rich color variations and elegant form, holds a significant position in the global floriculture industry, where the color of its petals and the content of anthocyanins are crucial for enhancing the plant’s ornamental value and market competitiveness. Nevertheless, the precise roles of the GST gene family in roses, especially regarding their participation in anthocyanin transport and the modulation of petal color, remain poorly elucidated. In the present investigation, we identified 83 rose glutathione S-transferase (GST) genes through whole-genome analysis. The identification and functional analysis of RcGSTF2 were conducted exclusively in the ‘Old Blush’ cultivar of Rosa chinensis. We employed bioinformatics, tissue expression analysis, subcellular localization, and transient expression validation to explore the function of the RcGSTF2 gene in anthocyanin transport and accumulation. We found that RcGSTF2 is closely related to anthocyanin-associated GSTs and demonstrated a conserved domain with high sequence similarity. Molecular docking analysis revealed potential binding modes between RcGSTF2 and cyanidin-3,5-diglucoside, suggesting a role in anthocyanin transport. Subcellular localization indicated that RcGSTF2 is associated with the cell membrane. Overexpression of RcGSTF2 in rose plants significantly increased anthocyanin accumulation, while silencing RcGSTF2 reduced anthocyanin content, highlighting its crucial role in regulating anthocyanin accumulation. This research investigates the functions of the GST gene family in roses, laying the groundwork for developing more colorful and resilient rose cultivars, with the functional analysis of RcGSTF2 being a key contribution to the floriculture industry’s genetic enhancement efforts. Full article