Search Results (476)

Food security and food safety are major aspects for human and animal health, yet mycotoxins contaminate 60–80% of food crops before and after harvest, elevating the risk of chronic toxicity and cancer development. This study investigates the potential of ferulic acid (FA) as an antioxidant against mycotoxin-induced oxidative stress in Caco-2 cells exposed to aflatoxin B1 (AFB1) and ochratoxin A (OTA) for 24 and 48 h. The effects on the degree of lipid peroxidation and non-enzymatic and enzymatic mechanisms against oxidative stress were evaluated. FA appears to mitigate oxidative stress by modulating lipid and protein oxidation, decreasing the level of 4-hydroxy-2-nonenal (4-HNE), increasing superoxide dismutase (SOD) activity, and preserving thiol groups by scavenging reactive oxygen species (ROS). Additionally, the reduction in polyubiquitinated Nrf2 level, and higher SOD activity, suggest that FA stabilizes Nrf2, delaying its degradation and reinforcing its antioxidant role. These findings indicate that FA partially counteracts mycotoxin-induced oxidative damage, highlighting the need for further investigation into its long-term effects. Full article

The central role of angiotensinogen in the control of blood pressure is revealed by a series of crystallographic structures, including complexes with renin. Specifically, the structures provide an understanding of the sequential molecular events that lead to the pre-eclamptic hypertensive crises of pregnancy. The release of the precursor vasopressor peptide from the amino-terminal tail of angiotensinogen appears to be modulated by a redox-sensitive disulphide bridge. Our findings indicate that the activation of the thiol-switch in the circulating maternal angiotensinogen occurs at the placental level in response to oxidative stress, exacerbated by placental insufficiency. We propose here that a contributory factor is the inherent redox stress accompanying the placental exchange of oxygenation between the haemoglobin of the mother (oxy-HbA) and the deoxygenated haemoglobin of the foetus (deoxy-HbF). Full article

Background: The thioredoxin system (TrxS) is crucial for maintaining redox balance by regulating cellular thiol levels and is involved in various biological processes, including cancer progression. Thioredoxin reductase (TrxR), a key component of TrxS, reduces oxidized thioredoxin (Trx) using NADPH. This study investigates the inhibitory effects of 2-bromo-2-nitro-1,3-propanediol (Bronopol, BP), a preservative, on TrxR activity and its impact on cellular thiols and cell viability. Methods: Purified recombinant TrxR and noncancer and cancer cells were treated with different concentrations of BP and TrxR activity measured. BP-treated cells were examined for effects of BP on total cellular thiol level and GSH/GSSG ratio. Results: BP effectively inhibited TrxR in a dose-dependent manner, an effect that was reversible with dithiothreitol (DTT). BP treatment significantly reduced total thiol levels, decreased the GSH/GSSG ratio, and increased reactive oxygen species (ROS) in cells. Additionally, BP decreased cell viability and induced apoptosis, as indicated by morphological changes and increased c-fos mRNA expression. Conclusions: These findings highlight BP’s potential as a TrxR inhibitor and its cytotoxicity toward both noncancer and cancer cells. The observed effects—TrxR inhibition, thiol oxidation, GSH/GSSG imbalance, and ROS accumulation—may underlie BP’s cytotoxicity. Further research is needed to explore the precise molecular mechanisms by which BP exerts these effects. Full article

Glyoxal (GO) is a reactive dicarbonyl derived endogenously from sugars and other metabolic reactions within cells. Numerous exogenous sources of this compound include tobacco smoking, air pollution, and food processing. GO is toxic to cells mainly due to its high levels and reactivity towards proteins, lipids, and nucleic acids. We speculate that glyoxal could be involved in erythrocyte protein damage and lead to cell dysfunction. The osmotic fragility and level of amino and carbonyl groups of membrane proteins of erythrocytes incubated for 24 h with GO were identified. The amount of thiol, amino, and carbonyl groups was also measured in hemolysate proteins after erythrocyte treatment with GO. In hemolysate, the level of glutathione, non-enzymatic antioxidant capacity (NEAC), TBARS, and activity of antioxidant enzymes was also determined. The study’s results indicated that GO increases erythrocyte osmotic sensitivity, alters the levels of glutathione and free functional groups in hemolysate proteins, and modifies the activity of antioxidant enzymes. Our findings indicate that GO is a highly toxic compound to human erythrocytes. Glyoxal at concentrations above 5 mM can cause functional changes in erythrocyte proteins and disrupt the oxidoreductive balance in cells. Full article

This study investigated specific winemaking procedures that could increase fermentation esters and volatile thiols in Chardonnay wine during fermentation. These compounds together are known to cause tropical fruit aromas. Two levels of pre-fermentative skin contact (10 °C for 18 h) (yes/no), two levels of β-lyase addition (40 μL/L) (yes/no), and three levels of fermentation gradient temperature, FG0 (constant 13 °C), FG1 (started at 20 °C and after 96 h dropped to 13 °C), and FG2 (started at 20 °C and after ~11.5 °Brix dropped to 13 °C), were evaluated using laboratory-scale ferments in a full factorial design. Esters and the volatile thiols, 3-sulfanylhexan-1-ol (3SH), 3-sulfanylhexyl acetate (3SHA), and 4-methyl-4-sulfanylpentan-2-one (4MSP), were quantified using gas and liquid chromatography methods, respectively. The combination of skin contact and FG1 or FG2 resulted in the greatest levels of esters and thiols in Chardonnay wine. The fermentation gradient was shown to be efficient in reducing volatile compounds normally lost due to evaporation during fermentation. With these different processing techniques, it will be possible for winemakers to achieve different wine qualities depending on their chosen wine style. Full article

This study investigates the antioxidative potential of pomegranate peel extract (PPE) and prickly pear peel extract (HPE) as natural preservatives in cooked chicken models. The extracts were characterized for their phenolic and tannin content, and their antioxidant activity was measured through in vitro chemical assays using ABTS, DPPH, and FRAP assays. Cooked chicken samples were formulated with different concentrations of PPE or HPE and compared to sodium nitrite (NaNO₂) treatment. The effects on lipid and protein oxidation, instrumental colour parameters, and aldehyde formation were evaluated during storage. The results demonstrated that PPE exhibited higher antioxidant activity compared to HPE, particularly at higher concentrations. PPE_300 had the highest phenolic content, exhibited the strongest radical scavenging activity, and significantly reduced lipid oxidation markers such as malondialdehyde and lipid hydroperoxides. PPE also preserved protein integrity by reducing carbonyl formation and maintaining thiol levels. Colour stability was improved in both PPE- and HPE-treated samples, although nitrite remained the most effective in maintaining redness (a*-values). These findings suggest that PPE, particularly at 300 mg/kg, is a promising natural alternative to synthetic antioxidants for improving oxidative stability and shelf life in meat products. Further research should explore sensory attributes and consumer acceptance to facilitate industrial applications. Full article

Plant glutathione peroxidase-like (GPXL) enzymes are thiol-based peroxidases that reduce H₂O₂ or hydroperoxides to water or alcohols using electrons principally from thioredoxin. Arabidopsis thaliana possesses eight isoenzymes (AtGPXL1−8) located in different plant organelles and have various roles in redox-dependent processes. The determination of the redox potential of 6-day-old T-DNA insertional mutants (Atgpxl1–Atgpxl8) using a cytosolic redox-sensitive fluorescent probe (roGFP2) uncovered more oxidized redox status in the shoot and/or root of the untreated mutants, except for Atgpxl5. To investigate the involvement of AtGPXLs in the growth and abiotic stress responses of seedlings, the 4-day-old Atgpxls were exposed to salt and osmotic stresses for two weeks. The evaluation of the reactive oxygen species (ROS) levels of untreated 18-day-old plants using fluorescent microscopy revealed the elevated accumulation of total ROS in the shoots and, in some cases, the roots of the mutants. Regarding the growth of roots, both the length of primary roots and/or the number of lateral roots were affected by the mutation of AtGPXLs. A strong negative correlation was observed between the ROS level of wild type shoots and the development of lateral roots, but it was altered in mutants, while in the case of Atgpxl1, Atgpxl5, and Atgpxl7 seedlings, it disappeared; in other mutants (Atgpxl4, Atgpxl6, and Atgpxl8), the correlation became stronger. Our analysis underpins the discrete role of AtGPXL enzymes in controlling the growth and development of plants by fine tuning the ROS contents and redox status in an organ-specific way. Differences in root phenotype and metabolic activity between Atgpxl mutants and wild type plants highlight the essential role of AtGPXLs in ROS processing to support growth, which is particularly evident when one GPXL isoenzyme is absent or its activity is reduced, both under normal and abiotic stress conditions. Full article

Thiol-containing drugs may interact with a region of tropomyosin receptor kinase A (TrkA), potentially inhibiting its activation by nerve growth factor (NGF). This action has been linked to potential analgesic activities. Here, we describe the ability of erdosteine, a thiolic compound classified as a mucolytic agent, to bind to the TrkA receptor sequence in silico and its in vitro effects on TrkA activation induced by NGF in cultured human neuroblastoma cells. Our results show that erdosteine and its metabolite, Met-1, bind to the TrkA receptor pocket, involving the primary TrkA residues Glu331, Arg347, His298, and His297. Furthermore, Met-1 has the ability to reduce the disulfide bridge between Cys300 and Cys345 of TrkA. In vitro measurement of TrkA autophosphorylation following NGF activation confirmed that erdosteine and Met-1 interfere with NGF-induced TrkA activation, leading to a consequent loss of the molecular recognition and spatial reorganization necessary for the induction of the autophosphorylation process. This effect was inhibited by low millimolar concentrations of the two compounds, reaching a maximal inhibition (around 40%) after 24 h of exposure to 1 mM erdosteine, and then plateauing. These findings suggest that erdosteine can act as a TrkA antagonist, thus indicating that this drug may have potential as an analgesic via a novel non-opioid mechanism of action operating through NGF signaling inhibition at the level of TrkA. Full article

Objective: Joint injury precipitates post-traumatic osteoarthritis (PTOA) via chondrocyte mitochondrial oxidative damage. Carbon monoxide (CO) is a small molecule with potent antioxidant and mitochondrial benefits in other tissues that have not been explored in healthy chondrocytes. We hypothesized that CO would subvert the mitochondrial effects of articular cartilage injuries upon resident chondrocytes. Design: We evaluated intra-articular delivery of a novel carbon monoxide-containing foam (COF). We used in vitro impact injuries to explore mitochondrial and redox endpoints after CO exposure. We then applied intra-articular injections of COF or control room air foam (RAF) to assess safety, efficacy, and other intra-articular responses. Results: COF increased the expression of HO1 and mitofusin-1 within 1 h and this increase was sustained for 12 h in vitro. COF increased chondrocyte mitochondrial respiration by 40% and increased reduced (not oxidized) thiols by 50% following in vitro injury to osteochondral explants. After cartilage injury, COF prevented the formation of 3-nitrotyrosine and the loss of articular chondrocyte mitochondria. When injected intra-articularly, COF was retained for 24 h post-injection in mouse stifle joints. It increased HO1 in those joints, enhanced reduced thiol levels in rabbit stifle joints, and exhibited no toxicity 1 and 4 weeks after injection. Conclusions: This study supports the hypothesis that CO functions as an antioxidant for articular chondrocytes by supporting mitochondria and intracellular GSH in the presence or absence of cartilage injury. Challenges in delivering exogenous CO have limited its preclinical development, but new CO-releasing materials like COF may enable new examinations of this promising small molecule. Full article

One potential association that is gaining increasing attention is the link between multiple sclerosis (MS) and migraine, which are suggested to frequently coexist in young patients. This is the first study to analyze the levels of multiple markers of oxidative stress in sociodemographically similar groups of patients with migraine, MS, and both MS and migraine. A single cross-sectional study was conducted at the Department of Neurology, Rzeszów University. The study included 110 participants, comprising 26 healthy controls, 24 subjects with migraines, 30 with MS, and 30 with both MS and migraine. Oxidative stress markers were measured in patients’ serum. Patients with MS and migraines had statistically elevated levels of 3-nitrotyrosine, Amadori products, 4-hydroxy-nonenal, and oxidative damage to amino acids. Moreover, we observed reduced levels of thiol groups and total antioxidant capacity in the serum of patients with MS and migraines compared to healthy controls. The co-occurrence of migraines in MS leads to greater oxidative stress than MS alone. The impact of chronic oxidative stress on both MS and migraines may exacerbate symptoms and deteriorate the quality of life. Full article

Background: Grape pomace (GP), a by-product of winemaking, is a rich source of bioactive polyphenols known for their antioxidant and anti-inflammatory properties. While the cardiovascular benefits of red grape pomace have received significant scientific attention, the therapeutic potential of white grape pomace remains largely unexplored, particularly in glucocorticoid-induced hypertension. Given the rising prevalence of hypertension and the oxidative-inflammatory mechanisms underlying its progression, this study investigates the effects of white GP on blood pressure regulation, oxidative stress, and pro-inflammatory cytokine expression in an experimental model of dexamethasone (DEXA)-induced hypertension (HTN). By focusing on white GP, this research addresses a significant gap in current knowledge and proposes a novel, sustainable approach to managing hypertension through valorising winemaking by-products. Methods: The first concentration used, GP1, was 795 mg polyphenols/kg bw, while the second concentration, GP2, was 397.5 mg polyphenols/kg bw. Results: White GP polyphenols extract in the DEXA_GP1 group had reduced systolic and diastolic blood pressure. The extract with a higher content of polyphenols (GP1) prevented the elevation of serum levels of total oxidative stress (TOS), malondialdehyde (MDA), and oxidative stress index (OSI), while the extract with a lower content of polyphenols (GP2) slightly reduced serum levels of MDA. Both concentrations of GP increased serum levels of NO and Total Thiols, significantly higher (p < 0.05) than in the group treated with lisinopril. The serum levels of tumour necrosis factor-alpha (TNF-α) increased in all groups where HTN was induced. Both doses of GP extract prevented the elevation of TNF-α. Heart tissue levels of the studied cytokines (TNF-α, interleukin (IL)-1β, and IL-6 were not influenced (p > 0.05) by either the HTN induction or the treatment administered. Conclusions: These findings suggest that grape pomace may serve as a promising nutraceutical intervention for hypertension management, particularly in conditions associated with oxidative stress. Full article

Oxybenzone, a common sunscreen ingredient, has been widely detected in various environmental matrices, posing significant ecological and health risks. The present study demonstrates, for the first time, the capacity of Pleurotus djamor to degrade oxybenzone in in vitro cultures. After 14 days of mycelial incubation, oxybenzone concentrations in the medium decreased from 25 mg to 1.5394 ± 0.095 mg. The final amount of oxybenzone in the mycelium after lyophilization was 6.2067 ± 0.2459 mg. Furthermore, oxybenzone addition significantly reduced biomass growth from 2.510 ± 0.6230 g to 1.4697 ± 0.0465 g. The transformation products in the dry mycelium and medium were assessed and identified using UPLC-Q-tof based on monoisotopic molecular mass and fragmentation spectra. In processes initiated by P. djamor, mainly acylated derivatives of oxybenzone were formed. Additionally, compounds with thiol and amino groups were identified. Alterations in antioxidant profiles (L-tryptophan, 6-methyl-D,L-tryptophan, p-hydroxybenzoic acid, ergosterol, lovastatin, L-phenylalanine, and ergothioneine) in response to oxybenzone exposure were observed. Our findings reveal significant changes in the antioxidant levels and biomass growth inhibition, underscoring the potential toxicological risks associated with oxybenzone. The observed reduction in oxybenzone concentration highlights the potential of P. djamor as an effective and environmentally friendly strategy for mitigating this pollutant. Full article

The objective was to determine whether dairy cows may activate traditional and alternative inflammatory pathways by consuming a combination of a phytogenic diet (essential oil and pepper resin). Twenty pregnant Jersey cows in the final (third) lactation phase (260 days in milk) were divided into two groups: control, with no additive consumption, and test, with the addition of the phytogenic to the concentrate portion of the diet (150 mg/day/kg dry matter). Blood samples were collected on experimental days 1, 7, 14, 21, 28, 35, and 42 by coccygeal vein puncture to assess the complete blood count, serum biochemistry of levels of total protein, albumin, and globulin, as well as carbohydrate metabolism (glucose), lipid metabolism (cholesterol and triglycerides), protein metabolism (urea), activities of hepatic enzymes (gamma-glutamyl transferase (GGT) and aspartate aminotransferase (AST)), cytokine levels (interleukins IL-1β, IL-6, and IL-10), antioxidant response [thiobarbituric acid reactive substances (TBARS), reactive oxygen species (ROS), total thiol (PSH), and non-protein thiol (NPSH), and glutathione S(GST)], cholinergic system [total cholinesterase (ChE) and acetylcholinesterase (AChE)], purinergic signaling [NTPDase, 5′ectonucleotidase and adenosine deaminase (ADA)], and energetic metabolism enzymes [creatine kinase (CK), pyruvate kinase (PK), and adenylate kinase (AK)]. Productive performance was assessed through feed intake and milk production. The results revealed that the use of phytogenic compounds significantly influenced the cholinergic system and purinergic signaling associated with immunology. The reduction in cholinesterase (ChE) activity and the increase in acetylcholinesterase (AChE) activity in lymphocytes suggest the modulation of the cholinergic system, enhancing the immune response. Furthermore, the elevated activity of adenosine deaminase (ADA) in lymphocytes and platelets, together with increased ATP and ADP hydrolysis in platelets, indicates the beneficial regulation of purinergic signaling, potentially contributing to inflammatory modulation. These effects were accompanied by a lower production of pro-inflammatory cytokines (IL-1β and IL-6) and a higher production of IL-10, reinforcing an anti-inflammatory profile. The reduced leukocyte and lymphocyte counts may reflect a lower inflammatory demand, while the increased levels of NPSH and GST antioxidants suggest cellular protection. Despite these physiological changes, productive performance and milk quality remained unaffected. In summary and practical terms, including this additive in the cows’ diet benefits the cow’s health in the final third of gestation when the animal already has a reduced immune response due to advanced gestation. Full article

Malignant melanoma, particularly amelanotic melanoma, contributes to a very serious problem in public health. One way to find new therapies is to learn about and understand the molecular pathways that regulate cancer growth and development. In the case of a tumor, the autophagy process can lead to the development or inhibition of cancer. This study aimed to assess the cytotoxicity of connection trametinib (MEK1 and MEK2 kinase inhibitor) with autophagy inhibitors—chloroquine (lysosomal clearance of autophagosomes inhibitor) and 3-methyladenine (phosphatidylinositol 3-kinases inhibitor), on two amelanotic melanoma cell lines (C32 and A-375). The results showed that combination therapy had better anti-proliferative effects than alone therapy in both cell lines. The C32 cell line was more sensitive to 3-methyladenine treatment (alone and in combinations), and the A375 line showed sensitivity to chloroquine and 3-methyladenine (alone and in combinations). The anti-proliferative effect was accompanied by dysregulation of the cell cycle, a decrease in the reduced thiols, the depolarization of the mitochondrial membrane and the level of p44/p42 MAPK. Both inhibitors have the ability to induce apoptosis. Differences in the level of LC3A/B and LC3B proteins between the chloroquine and the 3-methyladenine samples indicate that these drugs inhibit autophagy at different stages. The enhancement of the effect of trametinib by autophagy inhibitors suggests the possibility of combining drugs with anti-cancer potential with modulators of the autophagy process. Full article

Drawing soy protein (DSP) exhibits a well-defined fibrous structure, conferring significant market potential. This study investigates the interactions between DSP and myofibrillar proteins (MP) and their effects on gel properties. Porcine myofibrillar protein (MP) was used as the raw material, and mixed systems were prepared by incorporating different concentrations of DSP at 0%, 2%, 4%, 6%, and 8% to evaluate their physicochemical properties and gel characteristics. The results demonstrated that the addition of DSP enhanced the gel strength, hardness, and water-holding capacity (WHC) of MP, thereby improving the overall properties and water retention of the gels. Among them, the trend of change was most obvious when the addition amount was 6%. The gel strength increased by 196.5%, the water retention capacity improved by 68.3%, and the hardness rose by 33.3%. Furthermore, as the addition amount of DSP increases, the total thiol content decreases, the hydrogen bond content increases, and the surface hydrophobicity enhances. This leads to a more compact arrangement of protein molecules, which is conducive to a denser and more stable solution and improves the stability of the protein solution. The α-helical structures in the proteins progressively transformed into β-turn structures, exposing more amino acid side chains and inducing conformational changes in MP, resulting in denser and more uniform gel network structures. The most pronounced changes were observed at a 6% addition level. These findings contribute to diversifying meat products and provide a theoretical basis for improving the WHC and yield of emulsified meat products in pork processing. Full article