Search Results (722)

Cadmium (Cd) is a highly toxic heavy metal that disrupts development and reproduction, primarily through oxidative stress. In this context, sulforaphane (SFN), an antioxidant compound, may serve as a promising agent to counteract Cd-induced oxidative damage and prevent developmental and reproductive abnormalities. This study aimed to evaluate the effect of SFN on reproductive toxicity induced by cadmium chloride (CdCl₂) in the nematode Caenorhabditis elegans (C. elegans). Five experimental groups were established: (I) Control: no treatment, (II) dimethyl sulfoxide (DMSO): 48 h with 0.01% DMSO, (III) CdCl₂: 24 h with 4600 µM CdCl₂, (IV) SFN + CdCl₂: 24 h with 100 µM SFN followed by 24 h with both SFN and CdCl₂, and (V) SFN: 48 h with 100 µM SFN. Co-exposure to SFN and CdCl₂ prevented the reduction in the percentage of adult nematodes and increased egg-laying. It also significantly improved hatching rates, allowing more embryos to reach the larval stage, and prevented reductions in body size. However, no effects were observed on glutathione S-transferase-4 (GST-4) levels in the transgenic CL2166 strain. In conclusion, SFN substantially prevents Cd-induced reproductive toxicity in C. elegans. Future studies should investigate the molecular mechanisms by which SFN enhances egg-laying and offspring viability in this model. Full article

Glutathione S-transferases (GSTs) are phase II detoxification enzymes that display several enzymatic activities, including transferase, peroxidase, reductase, and isomerase functions, as well as non-enzymatic roles (e.g., serving as binding proteins). Their complex functionality lies in the biotransformation of xenobiotics (e.g., pesticides, drugs) and certain endogenous compounds, primarily metabolites produced by phase I detoxification enzymes. Several plant-derived compounds have been shown to modulate the activity and expression levels of these enzymes. Phytochemical activators of GSTs are potentially beneficial for detoxification in cases of exposure to various toxic compounds, whereas inhibitors of GSTs could have positive effects as adjuvant treatments for cancers that express high levels of GSTs associated with drug resistance. Full article

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

This study evaluates the influence of general anesthesia (GA) and spinal anesthesia (SA) on physiological and oxidative stress in parturients undergoing elective cesarean section, one of the most frequently performed surgical procedures worldwide. A total of 101 pregnant women were included, categorized into GA (n = 51) and SA (n = 50) groups. Blood samples were collected at three time points: one hour before surgery (Measurement 1), at umbilical cord clamping (Measurement 2), and two hours post-surgery (Measurement 3). Biomarkers of oxidative stress, complete blood count, and levels of biochemical parameters were measured. In second and/or third measurement, biochemical blood analysis showed increased prolactin and cortisol levels, followed by spike of glucose and insulin in the GA group. However, levels of tri-iodothyronine were reduced in both groups in the third measurement. Glutathione S-transferase (GST) activity was increased in both groups in third measurement. The results showed increased concentrations of total SH groups and decreased concentrations of non-protein SH groups in the GA group during Measurement 2. Lymphocyte count was found to be predictor of GST levels. The results indicate more a pronounced endocrine response in GA group and speak in favor of spinal anesthesia. Both kinds of anesthesia are equally safe in terms of the oxidative status of the tissue. Full article

Forensic entomotoxicology is a subdiscipline that utilizes necrophagous insects as bioindicators for detecting drugs and toxicants in decomposed remains, particularly in cases where conventional biological matrices are no longer available. Toxic substances can profoundly alter insect development, physiology, and community succession, potentially impacting the accuracy of postmortem interval (PMI) estimation. This review systematically summarizes the effects of various xenobiotics, including pesticides, illicit drugs, sedatives, heavy metals, and antibiotics on larval growth, physiological traits, and gut microbial composition in forensically relevant flies. However, most studies to date have relied primarily on phenotypic observations, with limited insight into underlying molecular mechanisms. Significant interspecies and dose-dependent variability also exists in the absorption, metabolism, and physiological responses to xenobiotics. We highlight recent advances in multi-omics technologies that facilitate the identification of molecular biomarkers associated with xenobiotic exposure, particularly within the insect detoxification system. Key components such as cytochrome P450 monooxygenases (P450s), glutathione S-transferases (GSTs), and ATP-binding cassette (ABC) transporters play essential roles in xenobiotic metabolism and insecticide resistance. Additionally, the insect fat body serves as a central hub for detoxification, hormonal regulation, and energy metabolism. It integrates signals related to xenobiotic exposure and modulates larval development, making it a promising model for future mechanistic studies in insect toxicology. Altogether, this review offers a comprehensive and reliable framework for understanding the complex interactions between toxic substance exposure, insect ecology, and decomposition in forensic investigations. 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

This study investigated the ecotoxicological impacts of environmentally relevant concentrations (0.05, 0.50, and 5.00 mg/L) of nickel nanoparticles (Ni-NPs) by assessing oxidative stress biomarkers. The worm Hediste diversicolor, the bivalve Mytilus spp., and the fish Sparus aurata were chronically exposed to Ni-NPs for 28 days, and glutathione S-transferases (GST), catalase (CAT), and thiobarbituric acid reactive substances (TBARS) levels were measured to evaluate biochemical responses. GST activity increased in H. diversicolor and the liver of S. aurata, suggesting a key role for this enzyme in Ni-NPs detoxification. CAT activity was inhibited in the digestive gland of Mytilus spp. at the highest Ni-NPs concentration, indicating possible disruption of antioxidant defense. TBARS levels rose significantly in the gills of Mytilus spp. exposed to high Ni-NP concentrations, suggesting oxidative damage beyond detoxification capacity. In contrast, TBARS decreased in the digestive gland of Mytilus and in H. diversicolor, possibly due to compensatory upstream antioxidant responses. These findings indicate that each species exhibits distinct adaptive responses to Ni-NP exposure. Overall, this study highlights the need to consider species- and tissue-specific responses when performing ecotoxicological risk assessments of nanomaterials. Full article

Plastic pollution poses a massive problem to the environment, particularly seas and oceans. Microplastics (MPs) ingestion by marine species can generate many adverse effects, including causing oxidative stress. This study evaluated the effects of anthropic activity-related MP presence in two coastal fish species—Serranus scriba (more related to rocky bottoms) and Lithognathus mormyrus (more related to sandy bottoms)—in two areas of Mallorca Island (Western Mediterranean) with varying anthropic pressures with similar mixed rocky/sandy bottoms. A total of eight fish samples per species and per area (total n = 32), as well as three water samples (500 mL each) and three sediment samples per area, were collected and analyzed. The results showed that despite plastic presence in both areas, the area with higher tourism affluence was also the most polluted. Fourier transform infrared spectroscopy analysis confirmed that the majority of recovered polymers were polyethylene and polypropylene. The pattern of MPs presence was reflected in the biomarker analysis, which showed higher values of antioxidants, namely catalase (CAT) and superoxide dismutase (SOD); detoxification, namely glutathione s-transferase (GST); and inflammation, namely myeloperoxidase (MPO)—enzymes in the gastrointestinal tract of fish from the more polluted area. However, no statistical differences were found for malondialdehyde (MDA) as a marker of lipid peroxidation. As for differences between species, S. scriba presented a higher presence of MPs and measured biomarkers than in L. Mormyrus, suggesting higher exposure. In conclusion, these results showed that increased anthropic activity is associated with a higher presence of MPs which, in turn, induces an adaptative response in exposed fish. Moreover, species living in the same area could be differentially affected by MPs, which is probably associated with different behavioural and feeding habits. Full article

Utilizing a multi-biomarker approach, we assessed the potential adverse effects of pollutants on subcellular responses in the digestive gland of the freshwater mussel Unio crassus from a historically contaminated lowland section (KIZ) of the river Mrežnica compared to its less impacted upstream karstic section (REF) and their seasonality (spring vs. autumn). This approach accounted for the diverse modes of action of pollutants by including biomarkers of metal exposure (metallothioneins, MT), general stress (total cytosolic proteins, TP), antioxidative capacity (catalase, CAT; glutathione, GSH; glutathione-S-transferase, GST), oxidative damage (malondialdehyde, MDA), and neurotoxicity (acetylcholinesterase, AChE). Only in spring, MT concentrations were 15% higher at the REF site (4.38 ± 1.06 µg mg proteins⁻¹) compared to the KIZ site (3.69 ± 0.63 µg mg proteins⁻¹), likely related to elevated Cd bioaccumulation due to the karstic substrate. Regardless of the season, mussels from KIZ showed consistently lower TP and GSH, with significantly higher CAT, GST, and MDA levels, indicating elevated stress, activation of antioxidant defenses, and oxidative damage from chronic exposure to pro-oxidant pollutants, including metal(loid)s and organic contaminants (e.g., ibuprofen, nicotine). Compared to the REF site, AChE activity at the KIZ site was higher in late spring and lower in early autumn, indicating seasonal variability in AChE activity at the contamination-impacted location driven by fluctuating exposure to neurotoxicants, such as drugs and insecticides. Overall, biomarker responses indicated that mild historical pollution, reinforced by current low-capacity sources, has an observable impact on mussel health, posing long-term risks to sediment-dwelling aquatic organisms. 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 development of resistance to standard cytostatics, such as 5-fluorouracil (5-FU), significantly limits the efficacy of colon cancer therapy, prompting the search for novel anticancer agents, particularly among natural compounds. This study evaluated the anticancer effects of isorhamnetin, a plant-derived flavonol, and its ability to modulate the expression of drug-resistance-related biomarkers in SW-480 and HT-29 colon cancer cells, with a focus on ATP-binding cassette (ABC) transporters. Isorhamnetin demonstrated strong cytotoxic and proapoptotic activity on both cell lines, while showing lower toxicity toward normal HaCaT cells. In addition to suppressing the mRNA expression of drug-metabolizing enzymes (CYP1A1 and CYP1B1), isorhamnetin significantly reduced the mRNA levels of multidrug resistance-associated proteins 1 and 5 (MRP1 and MRP5), as well as the P-glycoprotein (P-gp) level in SW-480 and HT-29 cells. Molecular docking analysis revealed a high binding affinity of isorhamnetin to CYP1A1, CYP1B1, P-gp, MRP1, MRP5, and glutathione S-transferase (GST) proteins, with stronger interactions than those observed for 5-FU, suggesting potential interference with their function. These results provide a solid basis for future investigations to confirm the therapeutic potential of isorhamnetin as a modulator of drug resistance in colon cancer cells. Full article

This study investigated the impact of sublethal concentrations of dinotefuran on the predatory behavior and detoxification enzyme activity of Harmonia axyridis, aiming to establish a theoretical foundation for the conservation and utilization of natural enemies and the effective management of wheat aphids. This study treated wheat aphids with sublethal concentrations (LC₂₀ and LC₃₀) of dinotefuran via the leaf dipping method and subsequently used them as prey for the fourth-instar larvae of H. axyridis. The predation amount, instantaneous attack rate, handling time, daily maximum predation amount, and detoxification enzyme activity of H. axyridis were statistically analyzed. The results indicated that the predation of H. axyridis on wheat aphids conformed to the Holling II disc equation. Moreover, in comparison to the control group, the handling time of H. axyridis on wheat aphids was extended, and at the same time, the instantaneous attack rate, maximum daily predation amount, and predation efficiency were all diminished. After the ingestion of LC₂₀- and LC₃₀-dinotefuran-treated aphids, the carboxylesterase levels in H. axyridis were not significantly different from the control, with levels 0.97-fold and 0.94-fold that of the control, respectively. Glutathione-S-transferase (GST) demonstrated an induction impact compared to the control, reaching 1.96- and 1.47-fold higher than the control, respectively. The activity of mixed-functional oxidase (MFO) demonstrated an induction effect compared to the control, measuring 1.98- and 3.04-fold higher than that of the control, respectively. Consequently, the predation function and detoxification enzyme activity of H. axyridis were influenced when consuming wheat aphids treated with sublethal concentrations of dinotefuran, with significant variations across different concentrations, potentially reflecting the survival strategy of insects under dinotefuran stress. Full article